U.S. patent application number 10/254154 was filed with the patent office on 2004-01-08 for amidocarboxylic acid compounds.
This patent application is currently assigned to SANKYO COMPANY, LTD. Invention is credited to Fujiwara, Toshihiko, Sakurai, Mitsuya, Takamura, Makoto, Yanagisawa, Hiroaki.
Application Number | 20040006141 10/254154 |
Document ID | / |
Family ID | 17479094 |
Filed Date | 2004-01-08 |
United States Patent
Application |
20040006141 |
Kind Code |
A1 |
Yanagisawa, Hiroaki ; et
al. |
January 8, 2004 |
Amidocarboxylic acid compounds
Abstract
Amidocarboxylic acid compounds of the formula: 1 wherein R.sup.1
represents hydrogen or alkyl; R.sup.2 represents alkylene; R.sup.3
represents hydrogen, alkyl, alkoxy, alkylthio, halogen, nitro,
dialkylamino, aryl, aralkyl, hydroxyl or acyl; R.sup.4 represents
hydrogen or alkyl; X represents an aryl or hetero aryl; Y
represents a single bond, oxygen, sulfur or N--R.sup.5, wherein
R.sup.5 is hydrogen, alkyl, aliphatic acyl or aromatic acyl; Z
represents alkylene; and W represents alkyl, hydroxyl, alkoxy,
alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkyloxy,
aralkylthio, aryloxyalkyl, hetero aryl, hetero aryloxy, hetero
alkylthio, heterocyclic, amino, alkylamino, N-alkyl-N-arylamino,
arylamino, aralkylamino or aralkyloxycarbonylamino. The compounds
are used to treat diabetes mellitus, hyperlipemia,
arteriosclerosis, obesity, impaired glucose tolerance,
insulin-resistant non-IGT, fatty liver, diabetic complications,
gestational diabetes mellitus, polycystic ovary syndrome,
atherosclerosis, arthrosteitis, rheumatic arthritis, allergic
diseases, asthma, cancer, autoimmune diseases, pancreatitis and
cataracts.
Inventors: |
Yanagisawa, Hiroaki; (Tokyo,
JP) ; Sakurai, Mitsuya; (Abiko-shi, JP) ;
Takamura, Makoto; (Kawasaki-shi, JP) ; Fujiwara,
Toshihiko; (Ebina-shi, JP) |
Correspondence
Address: |
FRISHAUF, HOLTZ, GOODMAN & CHICK, P.C.
767 Third Avenue - 25th Floor
New York
NY
10017-2023
US
|
Assignee: |
SANKYO COMPANY, LTD
Tokyo
JP
|
Family ID: |
17479094 |
Appl. No.: |
10/254154 |
Filed: |
September 25, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10254154 |
Sep 25, 2002 |
|
|
|
09540765 |
Mar 30, 2000 |
|
|
|
09540765 |
Mar 30, 2000 |
|
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PCT/JP98/04396 |
Sep 30, 1998 |
|
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Current U.S.
Class: |
514/567 ;
562/450 |
Current CPC
Class: |
A61P 3/00 20180101; C07D
213/20 20130101; C07C 235/48 20130101; C07C 235/42 20130101; C07D
215/54 20130101; C07D 213/82 20130101; C07D 213/64 20130101; C07D
413/12 20130101; C07D 295/155 20130101; C07C 233/69 20130101; C07C
235/84 20130101; C07D 209/30 20130101; C07C 237/32 20130101; A61P
29/00 20180101 |
Class at
Publication: |
514/567 ;
562/450 |
International
Class: |
A61K 031/195; C07C
237/20 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 2, 1997 |
JP |
HEI 9-269923 |
Claims
1. An amidocarboxylic acid derivative of formula (I): 14wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms and aralkyl groups having from 7 to 12 carbon atoms; R.sup.2
is selected from the group consisting of straight or branched chain
alkylene groups having from 1 to 6 carbon atoms; R.sup.3 is
selected from the group consisting of (i) hydrogen atoms, (ii)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (iii) straight or branched chain alkoxy groups having from 1
to 4 carbon atoms, (iv) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro
groups, (vii) straight or branched chain dialkylamino groups in
which each of said alkyl groups may be the same or different and
each has from 1 to 4 carbon atoms, (viii) aryl groups having from 6
to 10 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below, (ix) aralkyl groups having
from 7 to 12 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety, (x) hydroxyl groups and (xi) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms; Z
is selected from the group consisting of straight or branched chain
alkylene group having from 1 to 6 carbon atoms; W is selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below, (vi) aryloxy groups having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety, (vii) arylthio groups having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety, (viii) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (xi) aryloxyalkyl groups in which said
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the groups consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic,
5- to 10-membered hetero arylthio groups containing from 1 to 4
hetero atoms selected from the groups consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the groups consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xvi) amino groups, (xvii)
straight or branched chain monoalkylamino groups in which said
alkyl moiety has from 1 to 4 carbon atoms, (xviii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (xix) N-alkyl-N-arylamino groups in which said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms and said aryl moiety is an aryl group having from 6
to 10 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below, (xx) arylamino groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (xxi) aralkylamino groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety and (xxii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms and which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety; X is selected from the group consisting of aryl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha. defined below and
mono- or dicyclic, 5- to 10-membered hetero aryl groups having from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and and a sulfur atom which may have from 1
to 3 substituents selected from substituents .alpha. defined below,
when W represents a substituent selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) hydroxyl groups, (iii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight
or branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below, (vi) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety, (vii) arylthio groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (x) aralkylthio groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below and
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, or X is selected from the group consisting of aryl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha. defined below when
W is selected from the group consisting of (i) amino groups, (ii)
straight or branched chain monoalkylamino groups in which said
alkyl moiety has from 1 to 4 carbon atoms, (iii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (iv) N-alkyl-N-arylamino groups in which said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms and said aryl moiety has from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (v) arylamino groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (vi)
aralkylamino groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety and (vii) aralkyloxycarbonylamino groups
in which said aralkyl moiety has from 7 to 12 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety; said substituents
.alpha. are selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha. defined below, (x) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (xi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano
groups, (xv) amino groups, (xvi) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which said alkoxy moiety has from 1 to 4 carbon atoms,
(xiii) aralkyloxycarbonylamino groups in which said aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, (xx) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta. defined below on
said aryl moiety, (xxi) aryl groups having from 6 to 10 carbon
atoms and which may have from 1 to 3 substituents selected from
substituents .beta., which may be the same or different, defined
below, (xxii) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents .beta.
defined below on said aryl moiety, (xxiii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .beta. defined below on said aryl
moiety, (xxiv) arylsulfonyl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said aryl moiety, (xxv) arylsulfonylamino
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta. defined below on
said aryl moiety (the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xxvi) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .beta. defined below, (xxvii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below, (xxix) mono- or dicyclic, 5- to 10-membered
hetero arylsulfonyl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .beta. defined below, (xxx) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonylamino groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said hetero aryl moiety (the nitrogen atom
of said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms) and (xxxi) mono-
or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta. are selected from the group consisting of
(i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain hydroxyalkyl groups having from 1 to 4
carbon atoms, (viii) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x)
nitro groups, (xi) cyano groups, (xii) carboxyl groups, (xiii)
amino groups, (xiv) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms,
(xv) straight or branched chain dialkylamino groups in which said
alkyl moieties may be the same or different and each has from 1 to
4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups
having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups
in which said monoalkylamino moiety has one straight or branched
chain alkyl group having from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
which may be the same or different and each has from 1 to 4 carbon
atoms and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xix) straight or branched
chain alkoxycarbonylamino groups in which said alkoxy moiety has
from 1 to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in
which said aralkyl moiety has from 7 to 12 carbon atoms; and Y is
selected from the group consisting of a single bond, an oxygen
atom, a sulfur atom and a group of formula: >N--R.sup.5, wherein
R.sup.5 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, straight or branched chain aliphatic acyl groups having from
1 to 8 carbon atoms and aromatic acyl groups having from 7 to 11
carbon atoms; a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof; with the proviso that
the amidocarboxylic acid derivative does not include compounds
wherein: R.sup.1 is selected from the group consisting of hydrogen
atoms, straight or branched chain alkyl groups having from 1 to 6
carbon atoms and aralkyl groups having from 7 to 12 carbon atoms
which include a straight or branched chain alkyl group having 1 to
4 carbon atoms substituted with an aryl moiety; R.sup.2 is selected
from the group consisting of straight or branched chain alkylene
groups having from 1 to 6 carbon atoms; R.sup.3 is selected from
the group consisting of (i) hydrogen atoms, (ii) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii)
straight or branched chain dialkylamino groups in which each of
said alkyl groups are the same or different and each has from 1 to
4 carbon atoms, (viii) aryl groups having from 6 to 10 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below, (ix) aralkyl groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below on said aryl moiety, (x) hydroxyl groups and (xi)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 6 carbon atoms; Z is selected from the group consisting
of straight or branched chain alkylene group having from 1 to 6
carbon atoms; W is
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which are unsubstituted or have from 1 to 5
substituents selected from substituents .alpha.' defined below,
(vi) aryloxy groups having from 6 to 10 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (vii)
arylthio groups having from 6 to 10 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (viii)
aralkyl groups having from 7 to 12 carbon atoms which include a
straight or branched chain alkyl group having 1 to 4 carbon atoms
substituted with an aryl moiety which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below on said aryl moiety, (ix) aralkyloxy groups having
from 7 to 12 carbon atoms which are unsubstituted or have from 1 to
5 substituents selected from substituents .alpha.' defined below on
said aryl moiety, (x) aralkylthio groups having from 7 to 12 carbon
atoms which are unsubstituted or have from 1 to 5 substituents
selected from substituents .alpha.' defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which are unsubstituted
or have from 1 to 5 substituents selected from substituents
.alpha.' defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
pyridyl, (xiii) quinolyl, (xiv) amino groups, (xv) straight or
branched chain monoalkylamino groups in which said alkyl moiety has
from 1 to 4 carbon atoms, and (xvi) straight or branched chain
dialkylamino groups in which each of said alkyl moieties may be the
same or different and each has from 1 to 4 carbon atoms, X is a
phenyl group which is unsubstituted or has 1 to 3 substituents
.alpha.' defined below or a hetero aryl group selected from the
group consisting of pyridyl, quinolyl and isoquinolyl, said hetero
aryl group being unsubstituted or having from 1 to 3 substituents
selected from substituents .alpha.' defined below; said
substituents .alpha.' are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 3 substituents selected from substituents .beta.' defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which said alkyl moieties are the same or different and
each has from 1 to 4 carbon atoms, (xix) a phenyl group which is
unsubstituted or has 1 to 3 substituents .beta.' defined below and
(xx) a hetero aryl group selected from the group consisting of
pyridyl, quinolyl and isoquinolyl, said hetero aryl group being
unsubstituted or having from 1 to 3 substituents .beta.' defined
below; said substituents .beta.' are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups,
(xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which said alkyl moieties are the same or different and each has
from 1 to 4 carbon atoms, (xvi) straight or branched chain
aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups which are the same or
different and each has from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, and (xix) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms; and Y is selected from the group consisting of a
single bond, an oxygen atom, a sulfur atom and a group of formula:
>N--R.sup.5 wherein R.sup.5 is selected from the group
consisting of hydrogen atoms, straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, and straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms.
2. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms.
3. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms.
4. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom.
5. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.2 is a straight or
branched chain alkylene group having from 2 to 4 carbon atoms.
6. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.2 is an ethylene
group.
7. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having
one or two carbon atoms, alkylthio groups having one or two carbon
atoms, halogen atoms, nitro groups, hydroxyl groups and straight or
branched chain aliphatic acyl groups having from 1 to 5 carbon
atoms.
8. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is selected from the
group consisting of hydrogen atoms, halogen atoms and nitro
groups.
9. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is a hydrogen atom.
10. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms.
11. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is selected from the
group consisting of hydrogen atoms and methyl groups.
12. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is a hydrogen atom.
13. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Z is a straight or branched
chain alkylene group having from 1 to 4 carbon atoms.
14. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Z is a methylene group.
15. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.1 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (xi) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety
(the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms), (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety (the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms) and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms.
16. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.2 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (xi) aryloxyalkyl group in which
said aryl moiety is an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xiii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.2 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (xiii) aryl groups having from 6 to 10 carbon atoms
which may be the same or different and which have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xiv) aryloxy groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms.
17. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) aryloxy groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.3 defined below on said aryl
moiety, (iv) arylthio groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (v) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (vi) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vii)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (viii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha.hu 3 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups.
18. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) phenoxy groups which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.4 defined below on said phenyl moiety, (iv) phenylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.4 defined below
on said phenyl moiety, (v) aralkyl groups having from 7 to 10
carbon atoms, (vi) aralkyloxy groups having from 7 to 10 carbon
atoms, (vii) aryloxyalkyl groups in which said aryl moiety has from
6 to 10 carbon atoms and said alkyl moiety is straight or branched
chain and has from 1 to 4 carbon atoms, (viii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.4
are selected from the group consisting (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having one or two
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having one or two carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups.
19. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of phenoxy groups which may have one substituent
selected from substituents .alpha..sup.5 defined below on said
phenyl moiety; said substituents .alpha..sup.5 are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
20. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of phenoxy groups which may have one substituent
selected from substituents .alpha..sup.6 defined below on said
phenyl moiety; said substituents .alpha..sup.6 are selected from
the group consisting of methyl, ethyl, isopropyl, t-butyl,
trifluoromethyl, methoxy and trifluoromethoxy groups, and fluorine
atoms and chlorine atoms.
21. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.7 defined below; said
substituents .alpha..sup.7 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(x) straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (xi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (xiv) aralkyl groups having from 7 to 12 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xv) phenyl groups which may have from
1 to 3 substituents selected from substituents .beta..sup.3 defined
below, (xvi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xvii)
phenylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xviii)
phenylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xix)
phenylsulfonylamino groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below on said
phenyl moiety (the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety (the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms) and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms.
22. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.8 described below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.8 defined below; said
substituents .alpha..sup.8 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (viii) halogen atoms, (ix) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (x) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.4 defined
below, (xii) phenylthio groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xiii) furyl groups, (xiv) thienyl groups, (xv) oxazolyl groups,
(xvi) isoxazolyl groups, (xvii) thiazolyl groups, (xviii) pyridyl
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xix) imidazolyl groups,
the nitrogen atom of said imidazolyl groups may be substituted with
a straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xx) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.4 are selected from the
group consisting (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms.
23. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 described below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.9 defined below; said
substituents .alpha..sup.9 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
24. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of phenyl, indolyl, pyridyl and quinolyl groups, which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.11 defined below; said substituents .alpha..sup.11 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.7 described below, (vi) phenoxy groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.7
defined below, (vii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.7 defined below
and (viii) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.7 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
25. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of phenyl groups which may have one substituent selected
from substituents .alpha..sup.12 defined below; said substituents
.alpha..sup.12 are selected from the group consisting of methyl,
isopropyl and hydroxyl groups, fluorine atoms, chlorine atoms,
diethylamino and benzyl groups, phenyl groups, said phenyl groups
may be substituted with 1 to 3 substituents, which may be the same
or different, selected from the group consisting of methyl, ethyl,
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups,
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylamino and pyridyl groups, said pyridyl groups
may be substituted with a substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy,
isopropoxy and trifluoromethoxy groups, fluorine atoms, chlorine
atoms, and nitro, dimethylamino and diethylamino groups,
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropox- y and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups.
26. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of biphenylyl groups, each phenyl moiety may be
substituted with one substituent, which may be the same or
different, selected from the group consisting of methyl,
trifluoromethyl, hydroxyl, methoxy and hydroxymethyl groups,
fluorine atoms, chlorine atoms, and formyl, carboxyl, nitro,
dimethylamino and N,N-dimethylaminomethyl groups, a pyridylphenyl
group, said pyridyl moiety may be substituted with one substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms and nitro, dimethylamino and
diethylamino groups, and phenylpyridyl groups, said phenyl moiety
may be substituted with one substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy and
isopropoxy groups, fluorine atoms, chlorine atoms, and nitro and
dimethylamino group.
27. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Y is selected from the group
consisting of a single bond and an oxygen atom.
28. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Y is an oxygen atom.
29. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms, alkoxy
groups having one or two carbon atoms, alkylthio groups having one
or two carbon atoms, halogen atoms, nitro groups, hydroxyl groups
and straight or branched chain aliphatic acyl groups having from 1
to 5 carbon atoms; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a straight or branched chain
alkylene group having from 1 to 4 carbon atoms; W is selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (vii) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety,
(viii) aralkyl groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.1 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below; said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups (the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
30. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (vii) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety,
(viii) aralkyl groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(xix) imidazolyl groups (the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms) and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
31. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iii) aryloxy
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 described
below on the aryl moiety, (iv) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (v)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vi) aralkyloxy groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.3 defined below on said aryl
moiety, (vii) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.3 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (viii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.3
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups; X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.9 defined below; said
substituents .alpha..sup.9 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
32. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.5 defined below on said phenyl moiety; said
substituents .alpha..sup.5 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (v) straight or branched chain alkylthio groups
having one or two carbon atoms, (vi) straight or branched chain
alkylsulfonyl groups having from one or two carbon atoms, (vii)
halogen atoms, (viii) cyano groups and (ix) pyridyl groups; X is
selected from the group consisting of phenyl groups which may have
one substituent selected from substituents .alpha..sup.12 defined
below; said substituents .alpha..sup.12 are selected from the group
consisting of methyl, isopropyl and hydroxyl groups, fluorine
atoms, chlorine atoms, diethylamino and benzyl groups, phenyl
groups, said phenyl groups may be substituted with 1 to 3
substituents, which may be the same or different, selected from the
group consisting of methyl, ethyl, trifluoromethyl, hydroxyl,
methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups, phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino, N-methylphenylsulfonylami- no and pyridyl
groups, said pyridyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms, and nitro, dimethylamino
and diethylamino groups, pyridyloxy, pyridylthio, pyridylsulfonyl
and piperidyl groups; or X is selected from the group consisting of
pyridyl groups which may have one substituent selected from
substituents .alpha..sup.13 defined below; said substituents
.alpha..sup.13 are selected from the group consisting of methyl,
isopropyl, methoxy, ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropoxy
and benzyloxy groups, alkylthio groups having one or two carbon
atoms, alkylsulfonyl groups having one or two carbon atoms, benzyl
groups, phenyl groups, said phenyl groups may be substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups; and Y is an oxygen atom.
33. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.6 defined below on said phenyl moiety; said
substituents .alpha..sup.6 are selected from the group consisting
of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl, methoxy and
trifluoromethoxy groups, and fluorine atoms and chlorine atoms; X
is a biphenylyl group, the substituents of each phenyl moiety may
be the same or different and they are selected from the group
consisting of methyl, trifluoromethyl, hydroxyl, methoxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and formyl,
carboxyl, nitro, dimethylamino and N,N-dimethylaminomethyl groups),
a pyridylphenyl group, said pyridyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups, and phenylpyridyl groups
(said phenyl moiety may be substituted with one substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms, and nitro and dimethylamino groups; and Y is
an oxygen atom.
34. An amidocarboxylic acid derivative according to claim 1, a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 6 carbon atoms; R.sup.2 is a straight
or branched chain alkylene group having from 1 to 6 carbon atoms;
R.sup.3 is selected from the group consisting of (i) hydrogen
atoms, (ii) straight or branched chain alkyl groups having from 1
to 6 carbon atoms, (iii) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (viii) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents cc defined below and (ix) aralkyl groups having from 7
to 12 carbon atoms which may have from 1 to 3 substituents .alpha.
defined below on said aryl moiety; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 6 carbon atoms; Z is a straight or
branched chain alkylene group having from 1 to 4 carbon atoms; W is
selected from the group consisting of ethyl, propyl, butyl, pentyl,
methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio,
propylthio, isopropylthio, phenoxy, 4-methylphenoxy,
4-ethylphenoxy, 4-isopropylphenoxy, 4-methoxyphenoxy,
4-chlorophenoxy, phenylthio, benzyl, phenethyl, 3-phenylpropyl and
4-phenylbutyl groups; X is selected from the group consisting of
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha. defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below; said substituents .alpha. are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (vii) aralkyloxy groups having from 7 to 12 carbon atoms,
(viii) straight or branched chain alkylthio groups having from 1 to
4 carbon atoms, (ix) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (x) halogen atoms, (xi)
nitro groups, (xii) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and have
from 1 to 4 carbon atoms, (xiii) aralkyl groups having from 7 to 12
carbon atoms, (xiv) aryl groups having from 6 to 10 carbon atoms
(said aryl moiety may be substituted with a substituent selected
from the group consisting of straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
halogen atoms and straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms), (xv) aryloxy groups having from 6
to 10 carbon atoms (said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms), (xvi)
arylthio groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvii) arylsulfonyl groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xviii) arylsulfonylamino
groups having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, and the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xix) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xx) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxi) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonyl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xxiii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonylamino groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atom; and Y is selected from the group
consisting of a single bond, an oxygen atom, a sulfur atom and
groups of formula: >N--R.sup.5, wherein R.sup.5 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms and
aromatic acyl groups having from 7 to 11 carbon atoms.
35. An amidocarboxylic acid derivative according to claim 33,
wherein X is selected from the group consisting of an unsubstituted
biphenyl group, an unsubstituted pyridyl phenyl group and an
unsubstituted phenylpyridyl group.
36. An amidocarboxylic acid derivative according to claim 33,
wherein X is selected from the group consisting of an unsubstituted
biphenyl group and an unsubstituted pyridylphenyl group.
37. A pharmaceutical composition comprising an effective amount of
a pharmacologically effective compound together with a
pharmacologically acceptable diluent or carrier thereof, wherein
said pharmacologically effective compound is an amidocarboxylic
acid derivative of formula (I): 15wherein: R.sup.1 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms and aralkyl groups
having from 7 to 12 carbon atoms; R.sup.2 is selected from the
group consisting of straight or branched chain alkylene groups
having from 1 to 6 carbon atoms; R.sup.3 is selected from the group
consisting of (i) hydrogen atoms, (ii) straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight
or branched chain dialkylamino groups in which each of said alkyl
groups may be the same or different and each has from 1 to 4 carbon
atoms, (viii) aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (ix) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (x)
hydroxyl groups and (xi) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is selected
from the group consisting of straight or branched chain alkylene
group having from 1 to 6 carbon atoms; W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (vi) aryloxy groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (vii)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (viii) aralkyl groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (x) aralkylthio groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below and
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xvi) amino groups, (xvii) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which each of said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, (xix)
N-alkyl-N-arylamino groups in which said alkyl moiety is a straight
or branched chain alkyl group having from 1 to 4 carbon atoms and
said aryl moiety is an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (xx) arylamino groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (xxi)
aralkylamino groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety and (xxii) aralkyloxycarbonylamino groups
in which said aralkyl moiety has from 7 to 12 carbon atoms and
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety; X is selected from the
group consisting of aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below and mono- or dicyclic, 5- to 10-membered
hetero aryl groups having from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .alpha. defined below, when W represents a substituent
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below, (vi) aryloxy
groups having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (viii)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (ix) aralkyloxy groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (xi) aryloxyalkyl groups in which said
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the groups consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic,
5- to 10-membered hetero arylthio groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, or X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha. defined below when W is selected from the group consisting
of (i) amino groups, (ii) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms,
(iii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (iv) N-alkyl-N-arylamino groups in which
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms and said aryl moiety has from 6 to
10 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below, (v) arylamino groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (vi) aralkylamino groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety and (vii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety; said substituents .alpha. are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xiii) aralkyloxycarbonylamino groups in which
said aralkyl moiety has from 7 to 12 carbon atoms, (xix) straight
or branched chain dialkylamino groups in which said alkyl moieties
may be the same or different and each has from 1 to 4 carbon atoms,
(xx) aralkyl groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms and which may have from 1 to 3 substituents selected
from substituents .beta., which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta. defined below on said aryl moiety, (xxiii)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below on said aryl moiety, (xxiv) arylsulfonyl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta. defined below on said aryl moiety, (xxv)
arylsulfonylamino groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents .beta.
defined below on said aryl moiety (the nitrogen atom of said amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxvi) mono- or dicyclic,
5- to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below,
(xxvii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below, (xxviii) mono- or dicyclic, 5- to 10-membered
hetero arylthio groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta. defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below, (xxx)
mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said hetero aryl moiety, the nitrogen atom
of said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms and (xxxi) mono-
or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta. are selected from the group consisting of
(i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain hydroxyalkyl groups having from 1 to 4
carbon atoms, (viii) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x)
nitro groups, (xi) cyano groups, (xii) carboxyl groups, (xiii)
amino groups, (xiv) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms,
(xv) straight or branched chain dialkylamino groups in which said
alkyl moieties may be the same or different and each has from 1 to
4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups
having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups
in which said monoalkylamino moiety has one straight or branched
chain alkyl group having from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
which may be the same or different and each has from 1 to 4 carbon
atoms and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xix) straight or branched
chain alkoxycarbonylamino groups in which said alkoxy moiety has
from 1 to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in
which said aralkyl moiety has from 7 to 12 carbon atoms; and Y is
selected from the group consisting of a single bond, an oxygen
atom, a sulfur atom and a group of formula: >N--R.sup.5, wherein
R.sup.5 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, straight or branched chain aliphatic acyl groups having from
1 to 8 carbon atoms and aromatic acyl groups having from 7 to 11
carbon atoms; a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof; with the proviso that
the amidocarboxylic acid derivative does not include compounds
wherein: R.sup.1 is selected from the group consisting of hydrogen
atoms, straight or branched chain alkyl groups having from 1 to 6
carbon atoms and aralkyl groups having from 7 to 12 carbon atoms
which include a straight or branched chain alkyl group having 1 to
4 carbon atoms substituted with an aryl moiety; R.sup.2 is selected
from the group consisting of straight or branched chain alkylene
groups having from 1 to 6 carbon atoms; R.sup.3 is selected from
the group consisting of (i) hydrogen atoms, (ii) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii)
straight or branched chain dialkylamino groups in which each of
said alkyl groups are the same or different and each has from 1 to
4 carbon atoms, (viii) aryl groups having from 6 to 10 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below, (ix) aralkyl groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below on said aryl moiety, (x) hydroxyl groups and (xi)
straight or branched chain aliphatic acyl groups having from 1 to
5
carbon atoms; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 6 carbon atoms; Z is selected from the group consisting
of straight or branched chain alkylene group having from 1 to 6
carbon atoms; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) hydroxyl groups, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below, (vi) aryloxy groups having
from 6 to 10 carbon atoms which are unsubstituted or have from 1 to
5 substituents selected from substituents .alpha.' defined below on
said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon
atoms which are unsubstituted or have from 1 to 5 substituents
selected from substituents .alpha.' defined below on said aryl
moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms
which include a straight or branched chain alkyl group having 1 to
4 carbon atoms substituted with an aryl moiety which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xii) pyridyl, (xiii)
quinolyl, (xiv) amino groups, (xv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, and (xvi) straight or branched chain dialkylamino
groups in which each of said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, X is a phenyl
group which is unsubstituted or has 1 to 3 substituents .alpha.'
defined below or a hetero aryl group selected from the group
consisting of pyridyl, quinolyl and isoquinolyl, said hetero aryl
group being unsubstituted or having from 1 to 3 substituents
selected from substituents .alpha.' defined below; said
substituents .alpha.' are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 3 substituents selected from substituents .beta.' defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which said alkyl moieties are the same or different and
each has from 1 to 4 carbon atoms, (xix) a phenyl group which is
unsubstituted or has 1 to 3 substituents .beta.' defined below and
(xx) a hetero aryl group selected from the group consisting of
pyridyl, quinolyl and isoquinolyl, said hetero aryl group being
unsubstituted or having from 1 to 3 substituents .beta.' defined
below; said substituents .beta.' are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups,
(xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which said alkyl moieties are the same or different and each has
from 1 to 4 carbon atoms, (xvi) straight or branched chain
aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups which are the same or
different and each has from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, and (xix) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms; and Y is selected from the group consisting of a
single bond, an oxygen atom, a sulfur atom and a group of formula:
>N--R.sup.5 wherein R.sup.5 is selected from the group
consisting of hydrogen atoms, straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, and straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms.
38. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms.
39. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms.
40. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom.
41. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.2 is a straight or branched chain alkylene group having from
2 to 4 carbon atoms.
42. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.2 is an ethylene group.
43. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms, alkoxy groups having one or two carbon atoms, alkylthio
groups having one or two carbon atoms, halogen atoms, nitro groups,
hydroxyl groups and straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms.
44. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is selected from the group consisting of hydrogen atoms,
halogen atoms and nitro groups.
45. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is a hydrogen atom.
46. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms.
47. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is selected from the group consisting of hydrogen atoms and
methyl groups.
48. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is a hydrogen atom.
49. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms.
50. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Z
is a methylene group.
51. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below, (vi)
aryloxy groups having from 6 to 10 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below on said aryl
moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.1 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms.
52. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below, (vi)
aryloxy groups having from 6 to 10 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below on said aryl
moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl group in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms.
53. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
(iii) aryloxy groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (iv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (v) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vi)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vii) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero aryloxy
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(ix) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.3 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
54. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
(iii) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .alpha..sup.4 defined below on said
phenyl moiety, (iv) phenylthio groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.4 defined below on said phenyl moiety, (v)
aralkyl groups having from 7 to 10 carbon atoms, (vi) aralkyloxy
groups having from 7 to 10 carbon atoms, (vii) aryloxyalkyl groups
in which said aryl moiety has from 6 to 10 carbon atoms and said
alkyl moiety is straight or branched chain and has from 1 to 4
carbon atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero
aryloxy groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (ix) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.4 are selected from the
group consisting (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having one or two carbon atoms,
(vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
55. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of phenoxy groups which may
have one substituent selected from substituents .alpha..sup.5
defined below on said phenyl moiety; said substituents
.alpha..sup.5 are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain halogenated alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain alkylthio groups having one
or two carbon atoms, (vi) straight or branched chain alkylsulfonyl
groups having from one or two carbon atoms, (vii) halogen atoms,
(viii) cyano groups and (ix) pyridyl groups.
56. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of phenoxy groups which may
have one substituent selected from substituents .alpha..sup.6
defined below on said phenyl moiety; said substituents
.alpha..sup.6 are selected from the group consisting of methyl,
ethyl, isopropyl, t-butyl, trifluoromethyl, methoxy and
trifluoromethoxy groups, and fluorine atoms and chlorine atoms.
57. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.7 defined below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which ma) have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined
below: said substituents .alpha..sup.7 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (xiv) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (xv) phenyl groups which
may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvi) phenoxy groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xvii) phenylthio groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xviii) phenylsulfonyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents 3 defined below, (xxviii) pyridylsulfonyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xxix) imidazolyl groups (the nitrogen
atom of the ring of said imidazolyl groups may be substituted with
a straight or branched chain alkyl group having from 1 to 6 carbon
atoms), (xxx) pyridylsulfonylamino groups which may have from 1 to
3 substituents selected from substituents .beta..sup.3 defined
below on said pyridyl moiety, the nitrogen atom of said amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms and (xxxi) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.3 are selected from the group consisting of (i) straight
or branched chain alkyl groups having from 1 to 6 carbon atoms,
(ii) straight or branched chain halogenated alkyl groups having
from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain halogenated alkoxy groups having from 1
to 4 carbon atoms, (vi) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (vii) straight or branched
chain hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii)
halogen atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano
groups, (xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms.
58. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.8 described below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups (the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms) and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms.
59. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.9 described below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined
below; said substituents .alpha..sup.9 are selected from the group
consisting of (i) hydroxyl groups, (ii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iii) straight or
branched chain halogenated alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
60. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of phenyl, indolyl, pyridyl
and quinolyl groups, which may have from 1 to 3 substituents
selected from substituents .alpha..sup.11 defined below; said
substituents .alpha..sup.11 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.7 described
below, (vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.7 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.7 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.7 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
61. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of phenyl groups which may
have one substituent selected from substituents .alpha..sup.12
defined below; said substituents .alpha..sup.12 are selected from
the group consisting of methyl, isopropyl and hydroxyl groups,
fluorine atoms, chlorine atoms, diethylamino and benzyl groups,
phenyl groups, said phenyl groups may be substituted with 1 to 3
substituents, which may be the same or different, selected from the
group consisting of methyl, ethyl, trifluoromethyl, hydroxyl,
methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups, phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino, N-methylphenylsulfonylamino and pyridyl
groups, said pyridyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms, and nitro, dimethylamino
and diethylamino groups, pyridyloxy, pyridylthio, pyridylsulfonyl
and piperidyl groups; or X is selected from the group consisting of
pyridyl groups which may have one substituent selected from
substituents .alpha..sup.13 defined below; said substituents
.alpha..sup.13 are selected from the group consisting of methyl,
isopropyl, methoxy, ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropox-
y and benzyloxy groups, alkylthio groups having one or two carbon
atoms, alkylsulfonyl groups having one or two carbon atoms, benzyl
groups, phenyl groups, said phenyl groups may be substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups.
62. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of biphenylyl groups, each
phenyl moiety may be substituted with one substituent, which may be
the same or different, selected from the group consisting of
methyl, trifluoromethyl, hydroxyl, methoxy and hydroxymethyl
groups, fluorine atoms, chlorine atoms, and formyl, carboxyl,
nitro, dimethylamino and N,N-dimethylaminomethyl groups, a
pyridylphenyl group, said pyridyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups) and phenylpyridyl groups
(said phenyl moiety may be substituted with one substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms, and nitro and dimethylamino group.
63. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Y
is selected from the group consisting of a single bond and an
oxygen atom.
64. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Y
is an oxygen atom.
65. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, straight or branched chain alkyl groups having from
1 to 4 carbon atoms, alkoxy groups having one or two carbon atoms,
alkylthio groups having one or two carbon atoms, halogen atoms,
nitro groups, hydroxyl groups and straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 4 carbon atoms; Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) hydroxyl groups, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.1 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .alpha..sup.1
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano
groups, (xv) amino groups, (xvi) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which said alkoxy moiety has from 1 to 4 carbon atoms,
(xviii) aralkyloxycarbonylamino groups in which said aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below: said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
66. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, halogen atoms and nitro groups; R.sup.4 is selected
from the group consisting of hydrogen atoms and straight or
branched chain alkyl groups having from 1 to 4 carbon atoms; Z is a
methylene group; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) hydroxyl groups, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.2 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups, the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
67. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, halogen atoms and nitro groups; R.sup.4 is selected
from the group consisting of hydrogen atoms and straight or
branched chain alkyl groups having from 1 to 4 carbon atoms; Z is a
methylene group; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain alkoxy groups having from 1
to 4 carbon atoms, (iii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 described below on the aryl moiety, (iv)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (v) aralkyl groups having from 7
to 12 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.3 defined below on said aryl moiety,
(vi) aralkyloxy groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (vii) aryloxyalkyl
groups in which said aryl moiety is an aryl group having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.3 defined below and said alkyl moiety
is a straight or branched chain alkyl group having from 1 to 4
carbon atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero
aryloxy groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (ix) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below; said substituents .alpha..sup.9 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.5 defined below, (vi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.5 defined
below, (vii) pyridyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
68. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom; R.sup.2 is an ethylene group; R.sup.3
is a hydrogen atom; R.sup.4 is a hydrogen atom; Z is a methylene
group; W is a phenoxy group which may have one substituent selected
from substituents .alpha..sup.5 defined below on said phenyl
moiety; said substituents .alpha..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of phenyl groups
which may have one substituent selected from substituents
.alpha..sup.12 defined below; said substituents .alpha..sup.12 are
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups, said phenyl groups may be substituted
with 1 to 3 substituents, which may be the same or different,
selected from the group consisting of methyl, ethyl,
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups,
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylamino and pyridyl groups, said pyridyl groups
may be substituted with a substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy,
isopropoxy and trifluoromethoxy groups, fluorine atoms, chlorine
atoms, and nitro, dimethylamino and diethylamino groups,
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropox- y and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups are unsubstituted or substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy groups, fluorine
atoms, chlorine atoms, nitro, dimethylamino and diethylamino
groups; phenoxy; phenylthio; phenylsufonyl; phenylsulfonylamino and
N-methylphenylsulfonylamino groups; and Y is an oxygen atom.
69. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom; R.sup.2 is an ethylene group; R.sup.3
is a hydrogen atom; R.sup.4 is a hydrogen atom; Z is a methylene
group; W is a phenoxy group which may have one substituent selected
from substituents .alpha..sup.6 defined below on said phenyl
moiety; said substituents .alpha..sup.6 are selected from the group
consisting of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl,
methoxy and trifluoromethoxy groups, and fluorine atoms and
chlorine atoms; X is a biphenylyl group which is unsubstituted or
substituted, wherein the substituents of each phenyl moiety is the
same or different and are selected from the group consisting of
methyl, trifluoromethyl, hydroxyl, methoxy, hydroxymethyl groups,
fluorine atoms, chlorine atoms, formyl, carboxyl, nitro,
dimethylamino and N,N-dimethylaminomethyl groups; a pyridylphenyl
group, said pyridyl moiety being unsubstituted or substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups ; and phenylpyridyl groups,
said phenyl moiety being unsubstituted or substituted with one
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy groups, fluorine
atoms, chlorine atoms, nitro and dimethylamino groups; and Y is an
oxygen atom.
70. A pharmaceutical composition according to claim 37, comprising
a pharmacologically effective amount of an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms; R.sup.2 is a straight or branched chain alkylene group
having from 1 to 6 carbon atoms; R.sup.3 is selected from the group
consisting of (i) hydrogen atoms, (ii) straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight
or branched chain dialkylamino groups in which each alkyl group may
be the same or different and have from 1 to 4 carbon atoms, (viii)
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents .alpha. defined below and (ix) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha. defined below on said aryl moiety; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms; Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms; W is selected from the group consisting of ethyl,
propyl, butyl, pentyl, methoxy, ethoxy, propoxy, isopropoxy,
methylthio, ethylthio, propylthio, isopropylthio, phenoxy,
4-methylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy,
4-methoxyphenoxy, 4-chlorophenoxy, phenylthio, benzyl, phenethyl,
3-phenylpropyl and 4-phenylbutyl groups; X is selected from the
group consisting of aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below and mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .alpha. defined below; said substituents .alpha. are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain alkylenedioxy groups having
from 1 to 4 carbon atoms, (vii) aralkyloxy groups having from 7 to
12 carbon atoms, (viii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (ix) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (x) halogen
atoms, (xi) nitro groups, (xii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (xiii) aralkyl groups
having from 7 to 12 carbon atoms, (xiv) aryl groups having from 6
to 10 carbon atoms, said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms, (xv)
aryloxy groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvi) arylthio groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xvii) arylsulfonyl groups
having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (xviii) arylsulfonylamino groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, and the nitrogen atom of
said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms, (xix) mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xx) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xxi) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xxii) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (xxiii) mono- or dicyclic, 5-
to 10-membered hetero arylsulfonylamino groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, the nitrogen atom of said
amino moiety may be substituted with a straight or branched chain
alkyl group having from 1 to 6 carbon atoms; and Y is selected from
the group consisting of a single bond, an oxygen atom, a sulfur
atom and groups of formula: >N--R.sup.5, wherein R.sup.5 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain aliphatic acyl groups having from 1 to 8
carbon atoms and aromatic acyl groups having from 7 to 11 carbon
atoms.
71. A method of treating a warm-blooded animal in need thereof, to
(i) lower blood glucose, (ii) reduce lipid levels, (iii) ameliorate
insulin resistance, (iv) alleviate inflammatory diseases, (v)
achieve immunoregulation, (vi) inhibit aldose reductase, (vii)
inhibit 5-lipoxygenase, (viii) suppress generation of lipid
peroxide, (ix) activate peroxysome proliferator activated receptor,
or (x) alleviate osteoporosis, which method comprises administering
to said warm-blooded animal an effective amount of an active
ingredient, wherein said active ingredient is an amidocarboxylic
acid derivative of formula (I): 16wherein: R.sup.1 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms and aralkyl groups
having from 7 to 12 carbon atoms; R.sup.2 is selected from the
group consisting of straight or branched chain alkylene groups
having from 1 to 6 carbon atoms; R.sup.3 is selected from the group
consisting of (i) hydrogen atoms, (ii) straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight
or branched chain dialkylamino groups in which each of said alkyl
groups may be the same or different and each has from 1 to 4 carbon
atoms, (viii) aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (ix) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (x)
hydroxyl groups and (xi) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is selected
from the group consisting of straight or branched chain alkylene
group having from 1 to 6 carbon atoms; W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (vi) aryloxy groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (vii)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (viii) aralkyl groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (x) aralkylthio groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below and
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xvi) amino groups, (xvii) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which each of said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, (xix)
N-alkyl-N-arylamino groups in which said alkyl moiety is a straight
or branched chain alkyl group having from 1 to 4 carbon atoms and
said aryl moiety is an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (xx) arylamino groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (xxi)
aralkylamino groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety and (xxii) aralkyloxycarbonylamino groups
in which said aralkyl moiety has from 7 to 12 carbon atoms and
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety; X is selected from the
group consisting of aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below and mono- or dicyclic, 5- to 10-membered
hetero aryl groups having from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .alpha. defined below, when W represents a substituent
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below, (vi) aryloxy
groups having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (viii)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (ix) aralkyloxy groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (xi) aryloxyalkyl groups in which said
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the groups consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic,
5- to 10-membered hetero arylthio groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, or X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha. defined below when W is selected from the group consisting
of (i) amino groups, (ii) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms,
(iii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (iv) N-alkyl-N-arylamino groups in which
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms and said aryl moiety has from 6 to
10 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below, (v) arylamino groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (vi) aralkylamino groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety and (vii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety; said substituents .alpha. are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xiii) aralkyloxycarbonylamino groups in which
said aralkyl moiety has from 7 to 12 carbon atoms, (xix) straight
or branched chain dialkylamino groups in which said alkyl moieties
may be the same or different and each has from 1 to 4 carbon atoms,
(xx) aralkyl groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms and which may have from 1 to 3 substituents selected
from substituents .beta., which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta. defined below on said aryl moiety, (xxiii)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta. defined
below on said aryl moiety, (xxiv) arylsulfonyl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta. defined below on said aryl moiety, (xxv)
arylsulfonylamino groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents .beta.
defined below on said aryl moiety (the nitrogen atom of said amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxvi) mono- or dicyclic,
5- to 10 -membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below,
(xxvii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below, (xxviii) mono- or dicyclic, 5- to 10-membered
hetero arylthio groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta. defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below, (xxx)
mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said hetero aryl moiety, the nitrogen atom
of said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms and (xxxi) mono-
or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta. are selected from the group consisting of
(i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain hydroxyalkyl groups having from 1 to 4
carbon atoms, (viii) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x)
nitro groups, (xi) cyano groups, (xii) carboxyl groups, (xiii)
amino groups, (xiv) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms,
(xv) straight or branched chain dialkylamino groups in which said
alkyl moieties may be the same or different and each has from 1 to
4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups
having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups
in which said monoalkylamino moiety has one straight or branched
chain alkyl group having from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
which may be the same or different and each has from 1 to 4 carbon
atoms and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xix) straight or branched
chain alkoxycarbonylamino groups in which said alkoxy moiety has
from 1 to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in
which said aralkyl moiety has from 7 to 12 carbon atoms; and Y is
selected from the group consisting of a single bond, an oxygen
atom, a sulfur atom and a group of formula: >N--R.sup.5, wherein
R.sup.5 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, straight or branched chain aliphatic acyl groups having from
1 to 8 carbon atoms and aromatic acyl groups having from 7 to 11
carbon atoms; a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, with the proviso that
the amidocarboxylic acid derivative does not include compounds
wherein: R.sup.1 is selected from the group consisting of hydrogen
atoms, straight or branched chain alkyl groups having from 1 to 6
carbon atoms and aralkyl groups having from 7 to 12 carbon atoms
which include a straight or branched chain alkyl group having 1 to
4 carbon atoms substituted with an aryl moiety; R.sup.2 is selected
from the group consisting of straight or branched chain alkylene
groups having from 1 to 6 carbon atoms; R.sup.3 is selected from
the group consisting of (i) hydrogen atoms, (ii) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii)
straight or branched chain dialkylamino groups in which each of
said alkyl groups are the same or different and each has from 1 to
4 carbon atoms, (viii) aryl groups having from 6 to 10 carbon atoms
which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below, (ix) aralkyl groups having from 7 to 12 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below on said aryl moiety, (x)
hydroxyl groups and (xi) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is selected
from the group consisting of straight or branched chain alkylene
group having from 1 to 6 carbon atoms; W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which are unsubstituted or have from 1 to
5 substituents selected from substituents .alpha.' defined below on
said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon
atoms which include a straight or branched chain alkyl group having
1 to 4 carbon atoms substituted with an aryl moiety which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xii) pyridyl, (xiii)
quinolyl, (xiv) amino groups, (xv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, and (xvi) straight or branched chain dialkylamino
groups in which each of said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, X is a phenyl
group which is unsubstituted or has 1 to 3 substituents .alpha.'
defined below or a hetero aryl group selected from the group
consisting of pyridyl, quinolyl and isoquinolyl, said hetero aryl
group being unsubstituted or having from 1 to 3 substituents
selected from substituents .alpha.' defined below; said
substituents .alpha.' are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 3 substituents selected from substituents .beta.' defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which said alkyl moieties are the same or different and
each has from 1 to 4 carbon atoms, (xix) a phenyl group which is
unsubstituted or has 1 to 3 substituents .beta.' defined below and
(xx) a hetero aryl group selected from the group consisting of
pyridyl, quinolyl and isoquinolyl, said hetero aryl group being
unsubstituted or having from 1 to 3 substituents .beta.' defined
below; said substituents .beta.' are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups,
(xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which said alkyl moieties are the same or different and each has
from 1 to 4 carbon atoms, (xvi) straight or branched chain
aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups which are the same or
different and each has from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, and (xix) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms; and Y is selected from the group consisting of a
single bond, an oxygen atom, a sulfur atom and a group of formula:
>N--R.sup.5 wherein R.sup.5 is selected from the group
consisting of hydrogen atoms, straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, and straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms.
72. A method of treating according to claim 71, wherein said warm
blooded animal is a human.
73. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein R.sup.1 is selected from the
group consisting of hydrogen atoms straight or branched chain alkyl
groups having from 1 to 4 carbon atoms and aralkyl groups having
from 7 to 9 carbon atoms.
74. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms.
75. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom.
76. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.2 is a straight or
branched chain alkylene group having from 2 to 4 carbon atoms.
77. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.2 is an ethylene
group.
78. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having
one or two carbon atoms, alkylthio groups having one or two carbon
atoms, halogen atoms, nitro groups, hydroxyl groups and straight or
branched chain aliphatic acyl groups having from 1 to 5 carbon
atoms.
79. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is selected from the
group consisting of hydrogen atoms, halogen atoms and nitro
groups.
80. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.3 is a hydrogen atom.
81. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms.
82. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is selected from the
group consisting of hydrogen atoms and methyl groups.
83. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.4 is a hydrogen atom.
84. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Z is a straight or branched
chain alkylene group having from 1 to 4 carbon atoms.
85. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Z is a methylene group.
86. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.1 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (xi) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which ma) have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms.
87. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.2 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (xi) aryloxyalkyl group in which
said aryl moiety is an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xiii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.2 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (xiii) aryl groups having from 6 to 10 carbon atoms
which may be the same or different and which have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xiv) aryloxy groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms.
88. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) aryloxy groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.3 defined below on said aryl
moiety, (iv) arylthio groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (v) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (vi) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vii)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (viii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.3
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups.
89. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) phenoxy groups which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.4 defined below on said phenyl moiety, (iv) phenylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.4 defined below
on said phenyl moiety, (v) aralkyl groups having from 7 to 10
carbon atoms, (vi) aralkyloxy groups having from 7 to 10 carbon
atoms, (vii) aryloxyalkyl groups in which said aryl moiety has from
6 to 10 carbon atoms and said alkyl moiety is straight or branched
chain and has from 1 to 4 carbon atoms, (viii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.4
are selected from the group consisting (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having one or two
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having one or two carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups.
90. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of phenoxy groups which may have one substituent
selected from substituents .alpha..sup.5 defined below on said
phenyl moiety; said substituents .alpha..sup.5 are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
91. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: W is selected from the group
consisting of phenoxy groups which may have one substituent
selected from substituents .alpha..sup.6 defined below on said
phenyl moiety; said substituents .alpha..sup.6 are selected from
the group consisting of methyl, ethyl, isopropyl, t-butyl,
trifluoromethyl, methoxy and trifluoromethoxy groups, and fluorine
atoms and chlorine atoms.
92. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.7 defined below; said
substituents .alpha..sup.7 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(x) straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (xi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (xiv) aralkyl groups having from 7 to 12 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xv) phenyl groups which may have from
1 to 3 substituents selected from substituents .beta..sup.3 defined
below, (xvi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xvii)
phenylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xviii)
phenylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xix)
phenylsulfonylamino groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below on said
phenyl moiety, the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms.
93. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.8 described below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.8 defined below; said
substituents .alpha..sup.8 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (viii) halogen atoms, (ix) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (x) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.4 defined
below, (xii) phenylthio groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xiii) furyl groups, (xiv) thienyl groups, (xv) oxazolyl groups,
(xvi) isoxazolyl groups, (xvii) thiazolyl groups, (xviii) pyridyl
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xix) imidazolyl groups,
the nitrogen atom of said imidazolyl groups may be substituted with
a straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xx) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.4 are selected from the
group consisting (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms.
94. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 described below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.9 defined below; said
substituents .alpha..sup.9 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
95. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of phenyl, indolyl, pyridyl and quinolyl groups, which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.11 defined below; said substituents .alpha..sup.11 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.7 described below, (vi) phenoxy groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.7
defined below, (vii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.7 defined below
and (viii) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.7 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
96. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of phenyl groups which may have one substituent selected
from substituents .alpha..sup.12 defined below; said substituents
.alpha..sup.12 are selected from the group consisting of methyl,
isopropyl and hydroxyl groups, fluorine atoms, chlorine atoms,
diethylamino and benzyl groups, phenyl groups, said phenyl groups
may be substituted with 1 to 3 substituents, which may be the same
or different, selected from the group consisting of methyl, ethyl
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups,
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylamino and pyridyl groups, said pyridyl groups
may be substituted with a substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy,
isopropoxy and trifluoromethoxy groups, fluorine atoms, chlorine
atoms, and nitro, dimethylamino and diethylamino groups,
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropox- y and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups.
97. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: X is selected from the group
consisting of biphenylyl groups, each phenyl moiety may be
substituted with one substituent, which may be the same or
different, selected from the group consisting of methyl,
trifluoromethyl, hydroxyl, methoxy and hydroxymethyl groups,
fluorine atoms, chlorine atoms, and formyl, carboxyl, nitro,
dimethylamino and N,N-dimethylaminomethyl groups, a pyridylphenyl
group, said pyridyl moiety may be substituted with one substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms and nitro, dimethylamino and
diethylamino groups and phenylpyridyl groups, said phenyl moiety
may be substituted with one substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy and
isopropoxy groups, fluorine atoms, chlorine atoms, and nitro and
dimethylamino group.
98. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Y is selected from the group
consisting of a single bond and an oxygen atom.
99. A method of treating according to claim 72, wherein said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: Y is an oxygen atom.
100. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms and
aralkyl groups having from 7 to 9 carbon atoms; R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms; R.sup.3 is selected from the group consisting of hydrogen
atoms, straight or branched chain alkyl groups having from 1 to 4
carbon atoms, alkoxy groups having one or two carbon atoms,
alkylthio groups having one or two carbon atoms, halogen atoms,
nitro groups, hydroxyl groups and straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 4 carbon atoms; Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) hydroxyl groups, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.1 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .alpha..sup.1
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano
groups, (xv) amino groups, (xvi) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which said alkoxy moiety has from 1 to 4 carbon atoms,
(xviii) aralkyloxycarbonylamino groups in which said aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below; said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (x) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
101. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms and
aralkyl groups having from 7 to 9 carbon atoms; R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms; R.sup.3 is selected from the group consisting of hydrogen
atoms, halogen atoms and nitro groups; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms; Z is a methylene
group; W is selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
hydroxyl groups, (iii) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (v) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined
below, (vi) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.2 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups, the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
102. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms and
aralkyl groups having from 7 to 9 carbon atoms; R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms; R.sup.3 is selected from the group consisting of hydrogen
atoms, halogen atoms and nitro groups; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms; Z is a methylene
group; W is selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.3 described below on the aryl moiety, (iv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (v) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vi)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vii) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero aryloxy
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(ix) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.3 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below; said substituents .alpha..sup.9 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.5 defined below, (vi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.5 defined
below, (vii) pyridyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
103. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is a
hydrogen atom; R.sup.2 is an ethylene group; R.sup.3 is a hydrogen
atom; R.sup.4 is a hydrogen atom; Z is a methylene group; W is a
phenoxy group which may have one substituent selected from
substituents .alpha..sup.5 defined below on said phenyl moiety;
said substituents .alpha..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of phenyl groups
which may have one substituent selected from substituents
.alpha..sup.12 defined below; said substituents .alpha..sup.12 are
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups, said phenyl groups may be substituted
with 1 to 3 substituents, which may be the same or different,
selected from the group consisting of methyl, ethyl,
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups,
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylami- no and pyridyl groups, said pyridyl
groups may be substituted with a substituent selected from the
group consisting of methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms, and nitro, dimethylamino and diethylamino groups,
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropoxy and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups; and Y is an oxygen atom.
104. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is a
hydrogen atom; R.sup.2 is an ethylene group; R.sup.3 is a hydrogen
atom; R.sup.4 is a hydrogen atom; Z is a methylene group; W is a
phenoxy group which may have one substituent selected from
substituents .alpha..sup.6 defined below on said phenyl moiety;
said substituents .alpha..sup.6 are selected from the group
consisting of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl,
methoxy and trifluoromethoxy groups, and fluorine atoms and
chlorine atoms; X is a biphenylyl group, the substituents of each
phenyl moiety may be the same or different and they are selected
from the group consisting of methyl, trifluoromethyl, hydroxyl,
methoxy and hydroxymethyl groups, fluorine atoms, chlorine atoms,
and formyl, carboxyl, nitro, dimethylamino and
N,N-dimethylaminomethyl groups, a pyridylphenyl group, said pyridyl
moiety may be substituted with one substituent selected from the
group consisting of methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms and nitro, dimethylamino and diethylamino groups and
phenylpyridyl groups, said phenyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy and isopropoxy groups,
fluorine atoms, chlorine atoms, and nitro and dimethylamino groups;
and Y is an oxygen atom.
105. A method of treating according to claim 72, wherein said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms;
R.sup.2 is a straight or branched chain alkylene group having from
1 to 6 carbon atoms; R.sup.3 is selected from the group consisting
of (i) hydrogen atoms, (ii) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (iii) straight or branched chain
alkoxy groups having from l to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) halogen atoms, (vi) nitro groups, (vii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and have from 1 to 4 carbon atoms, (viii) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha. defined below and (ix) aralkyl groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
.alpha. defined below on said aryl moiety; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is a straight
or branched chain alkylene group having from 1 to 4 carbon atoms; W
is selected from the group consisting of ethyl, propyl, butyl,
pentyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio,
ethylthio, propylthio, isopropylthio, phenoxy, 4-methylphenoxy,
4-ethylphenoxy, 4-isopropylphenoxy, 4-methoxyphenoxy,
4-chlorophenoxy, phenylthio, benzyl, phenethyl, 3-phenylpropyl and
4-phenylbutyl groups; X is selected from the group consisting of
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha. defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below; said substituents .alpha. are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (vii) aralkyloxy groups having from 7 to 12 carbon atoms,
(viii) straight or branched chain alkylthio groups having from 1 to
4 carbon atoms, (ix) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (x) halogen atoms, (xi)
nitro groups, (xii) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and have
from 1 to 4 carbon atoms, (xiii) aralkyl groups having from 7 to 12
carbon atoms, (xiv) aryl groups having from 6 to 10 carbon atoms
(said aryl moiety may be substituted with a substituent selected
from the group consisting of straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
halogen atoms and straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms), (xv) aryloxy groups having from 6
to 10 carbon atoms, said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms), (xvi)
arylthio groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvii) arylsulfonyl groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xviii) arylsulfonylamino
groups having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, and the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xix) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xx) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxi) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonyl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xxiii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonylamino groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms; and Y is selected from the group
consisting of a single bond, an oxygen atom, a sulfur atom and
groups of formula: >N--R.sup.5 wherein R.sup.5 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms and
aromatic acyl groups having from 7 to 11 carbon atoms
106. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human.
107. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
amidocarboxylic acid derivative of formula (I), a pharmacologically
acceptable salt thereof or a pharmacologically acceptable ester
thereof, wherein: R.sup.1 is selected from the group consisting of
hydrogen atoms, straight or branched chain alkyl groups having from
1 to 4 carbon atoms and aralkyl groups having from 7 to 9 carbon
atoms; R.sup.2 is a straight or branched chain alkylene group
having from 2 to 4 carbon atoms; R.sup.3 is selected from the group
consisting of hydrogen atoms, straight or branched chain alkyl
groups having from 1 to 4 carbon atoms, alkoxy groups having one or
two carbon atoms, alkylthio groups having one or two carbon atoms,
halogen atoms, nitro groups, hydroxyl groups and straight or
branched chain aliphatic acyl groups having from 1 to 5 carbon
atoms; R.sup.4 is selected from the group consisting of hydrogen
atoms and straight or branched chain alkyl groups having from 1 to
4 carbon atoms; Z is a straight or branched chain alkylene group
having from 1 to 4 carbon atoms; W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.1 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (xi) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below; said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
108. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms and
aralkyl groups having from 7 to 9 carbon atoms; R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms; R.sup.3 is selected from the group consisting of hydrogen
atoms, halogen atoms and nitro groups; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms; Z is a methylene
group; W is selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
hydroxyl groups, (iii) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (v) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined
below, (vi) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.2 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups (the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms) and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
109. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms and
aralkyl groups having from 7 to 9 carbon atoms; R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms; R.sup.3 is selected from the group consisting of hydrogen
atoms, halogen atoms and nitro groups; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 4 carbon atoms; Z is a methylene
group; W is selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.3 described below on the aryl moiety, (iv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (v) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vi)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vii) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero aryloxy
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(ix) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.3 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below; said substituents .alpha..sup.9 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.5 defined below, (vi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.5 defined
below, (vii) pyridyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
110. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is a
hydrogen atom; R.sup.2 is an ethylene group; R.sup.3 is a hydrogen
atom; R.sup.4 is a hydrogen atom; Z is a methylene group; W is a
phenoxy group which may have one substituent selected from
substituents .alpha..sup.5 defined below on said phenyl moiety;
said substituents .alpha..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of phenyl groups
which may have one substituent selected from substituents
.alpha..sup.12 defined below; said substituents .alpha..sup.12 are
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups, said phenyl groups may be substituted
with 1 to 3 substituents, which may be the same or different,
selected from the group consisting of methyl, ethyl,
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups,
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylamino and pyridyl groups, said pyridyl groups
may be substituted with a substituent selected from the group
consisting of methyl, ethyl, trifluoromethyl, methoxy, ethoxy,
isopropoxy and trifluoromethoxy groups, fluorine atoms, chlorine
atoms, and nitro, dimethylamino and diethylamino groups,
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropox- y and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups; and Y is an oxygen atom.
111. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is a
hydrogen atom; R.sup.2 is an ethylene group; R.sup.3 is a hydrogen
atom; R.sup.4 is a hydrogen atom; Z is a methylene group; W is a
phenoxy group which may have one substituent selected from
substituents .alpha..sup.6 defined below on said phenyl moiety;
said substituents .alpha..sup.6 are selected from the group
consisting of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl,
methoxy and trifluoromethoxy groups, and fluorine atoms and
chlorine atoms; X is a biphenylyl group, the substituents of each
phenyl moiety may be the same or different and they are selected
from the group consisting of methyl, trifluoromethyl, hydroxyl,
methoxy and hydroxymethyl groups, fluorine atoms, chlorine atoms,
and formyl, carboxyl, nitro, dimethylamino and
N,N-dimethylaminomethyl groups, a pyridylphenyl group, said pyridyl
moiety may be substituted with one substituent selected from the
group consisting of methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms and nitro, dimethylamino and diethylamino groups,
and phenylpyridyl groups, said phenyl moiety may be substituted
with one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy and isopropoxy groups,
fluorine atoms, chlorine atoms, and nitro and dimethylamino groups;
and Y is an oxygen atom.
112. A method of treating according to claim 72, wherein said
treating comprises lowering blood glucose in said human and said
active ingredient is an amidocarboxylic acid derivative of formula
(I), a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, wherein: R.sup.1 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms;
R.sup.2 is a straight or branched chain alkylene group having from
1 to 6 carbon atoms; R.sup.3 is selected from the group consisting
of (i) hydrogen atoms, (ii) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) halogen atoms, (vi) nitro groups, (vii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and have from 1 to 4 carbon atoms, (viii) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents a defined below and (ix) aralkyl groups having from 7
to 12 carbon atoms which may have from 1 to 3 substituents .alpha.
defined below on said aryl moiety; R.sup.4 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 6 carbon atoms; Z is a straight or
branched chain alkylene group having from 1 to 4 carbon atoms; W is
selected from the group consisting of ethyl, propyl, butyl, pentyl,
methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio,
propylthio, isopropylthio, phenoxy, 4-methylphenoxy,
4-ethylphenoxy, 4-isopropylphenoxy, 4-methoxyphenoxy,
4-chlorophenoxy, phenylthio, benzyl, phenethyl, 3-phenylpropyl and
4-phenylbutyl groups; X is selected from the group consisting of
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha. defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below; said substituents .alpha. are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (vii) aralkyloxy groups having from 7 to 12 carbon atoms,
(viii) straight or branched chain alkylthio groups having from 1 to
4 carbon atoms, (ix) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (x) halogen atoms, (xi)
nitro groups, (xii) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and have
from 1 to 4 carbon atoms, (xiii) aralkyl groups having from 7 to 12
carbon atoms, (xiv) aryl groups having from 6 to 10 carbon atoms
(said aryl moiety may be substituted with a substituent selected
from the group consisting of straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
halogen atoms and straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (xv) aryloxy groups having from 6
to 10 carbon atoms, said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms), (xvi)
arylthio groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvii) arylsulfonyl groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xviii) arylsulfonylamino
groups having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, and the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xix) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xx) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxi) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonyl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xxiii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonylamino groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms; and Y is selected from the group
consisting of a single bond, an oxygen atom, a sulfur atom and
groups of formula: >N--R.sup.5, wherein R.sup.5 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms and
aromatic acyl groups having from 7 to 11 carbon atoms.
113. A method of treating according to claim 72, wherein said
treating comprises ameliorating insulin resistance.
114. A method of treating according to claim 72, wherein said
treating comprises alleviating an inflammatory disease.
115. A method of treating according to claim 72, wherein said
treating comprises achieving immunoregulation.
116. A method of treating according to claim 72, wherein said
treating comprises inhibiting aldose reductase.
117. A method of treating according to claim 72, wherein said
treating comprises inhibiting 5-lipoxygenase.
118. A method of treating according to claim 72, wherein said
treating comprises suppressing generation of lipid peroxide.
119. A method of treating according to claim 72, wherein said
treating comprises activating peroxysome proliferator activated
receptor.
120. A method of treating according to claim 72, wherein said
treating comprises alleviating osteoporosis.
121. A method for the therapy or prevention of a disease in a
warm-blooded animal selected from the group consisting of diabetes
mellitus, hyperlipemia, obesity, impaired glucose tolerance,
insulin-resistant non-IGT, fatty liver, diabetic complications,
arteriosclerosis, gestational diabetes mellitus, polycystic ovary
syndrome, atherosclerosis, arthrosteitis, rheumatic arthritis,
allergic diseases, asthma, cancer, autoimmune diseases,
pancreatitis and cataracts, which method comprises administering to
said warm-blooded animal a pharmacologically effective amount of an
active ingredient, wherein said active ingredient is an
amidocarboxylic acid derivative of formula (I): 17wherein: R.sup.1
is selected from the group consisting of hydrogen atoms, straight
or branched chain alkyl groups having from 1 to 6 carbon atoms and
aralkyl groups having from 7 to 12 carbon atoms; R.sup.2 is
selected from the group consisting of straight or branched chain
alkylene groups having from 1 to 6 carbon atoms; R.sup.3 is
selected from the group consisting of (i) hydrogen atoms, (ii)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (iii) straight or branched chain alkoxy groups having from 1
to 4 carbon atoms, (iv) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro
groups, (vii) straight or branched chain dialkylamino groups in
which each of said alkyl groups may be the same or different and
each has from 1 to 4 carbon atoms, (viii) aryl groups having from 6
to 10 carbon atoms which may have from 1 to 5 substituents selected
from substituents a defined below, (ix) aralkyl groups having from
7 to 12 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety, (x) hydroxyl groups and (xi) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms; Z
is selected from the group consisting of straight or branched chain
alkylene group having from 1 to 6 carbon atoms; W is selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below, (vi) aryloxy groups having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
selected from substituents .alpha. defined below on said aryl
moiety, (vii) arylthio groups having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety, (viii) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (xi) aryloxyalkyl groups in which said
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below and said alkyl moiety is a straight or
branched chain alkyl group having from 1 to 4 carbon atoms, (xii)
mono- or dicyclic, 5- to 10-membered hetero aryl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the groups consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic,
5- to 10-membered hetero arylthio groups containing from 1 to 4
hetero atoms selected from the groups consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the groups consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xvi) amino groups, (xvii)
straight or branched chain monoalkylamino groups in which said
alkyl moiety has from 1 to 4 carbon atoms, (xviii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (xix) N-alkyl-N-arylamino groups in which said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms and said aryl moiety is an aryl group having from 6
to 10 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below. (xx) arylamino groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (xxi) aralkylamino groups having from 7 to 12
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety and (xxii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms and which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety; X is selected from the group consisting of aryl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha. defined below and
mono- or dicyclic, 5- to 10-membered hetero aryl groups having from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and and a sulfur atom which may have from 1
to 3 substituents selected from substituents .alpha. defined below,
when W represents a substituent selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) hydroxyl groups, (iii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight
or branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below, (vi) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety, (vii) arylthio groups
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below on
said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety, (x) aralkylthio groups having from 7 to
12 carbon atoms which may have from 1 to 5 substituents selected
from substituents .alpha. defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents selected from substituents .alpha. defined below and
said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the groups consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, or X is selected from the group consisting of aryl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha. defined below when
W is selected from the group consisting of (i) amino groups, (ii)
straight or branched chain monoalkylamino groups in which said
alkyl moiety has from 1 to 4 carbon atoms, (iii) straight or
branched chain dialkylamino groups in which each of said alkyl
moieties may be the same or different and each has from 1 to 4
carbon atoms, (iv) N-alkyl-N-arylamino groups in which said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms and said aryl moiety has from 6 to 10 carbon atoms
which may have from 1 to 5 substituents selected from substituents
.alpha. defined below, (v) arylamino groups having from 6 to 10
carbon atoms which may have from 1 to 5 substituents selected from
substituents .alpha. defined below on said aryl moiety, (vi)
aralkylamino groups having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents selected from substituents .alpha. defined
below on said aryl moiety and (vii) aralkyloxycarbonylamino groups
in which said aralkyl moiety has from 7 to 12 carbon atoms which
may have from 1 to 5 substituents selected from substituents
.alpha. defined below on said aryl moiety; said substituents
.alpha. are selected from the group consisting of (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta. defined below, (x) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (xi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano
groups, (xv) amino groups, (xvi) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which said alkoxy moiety has from 1 to 4 carbon atoms,
(xiii) aralkyloxycarbonylamino groups in which said aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, (xx) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta. defined below on
said aryl moiety, (xxi) aryl groups having from 6 to 10 carbon
atoms and which may have from 1 to 3 substituents selected from
substituents .beta., which may be the same or different, defined
below, (xxii) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents .beta.
defined below on said aryl moiety, (xxiii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .beta. defined below on said aryl
moiety, (xxiv) arylsulfonyl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said aryl moiety, (xxv) arylsulfonylamino
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta. defined below on
said aryl moiety, the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xxvi) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .beta. defined below, (xxvii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta. defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below, (xxix) mono- or dicyclic, 5- to 10-membered
hetero arylsulfonyl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .beta. defined below, (xxx) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonylamino groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta. defined below on said hetero aryl moiety, the nitrogen atom
of said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms and (xxxi) mono-
or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta. are selected from the group consisting of
(i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain hydroxyalkyl groups having from 1 to 4
carbon atoms, (viii) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x)
nitro groups, (xi) cyano groups, (xii) carboxyl groups. (xiii)
amino groups, (xiv) straight or branched chain monoalkylamino
groups in which said alkyl moiety has from 1 to 4 carbon atoms.
(xv) straight or branched chain dialkylamino groups in which said
alkyl moieties may be the same or different and each has from 1 to
4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups
having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups
in which said monoalkylamino moiety has one straight or branched
chain alkyl group having from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
which may be the same or different and each has from 1 to 4 carbon
atoms and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xix) straight or branched
chain alkoxycarbonylamino groups in which said alkoxy moiety has
from 1 to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in
which said aralkyl moiety has from 7 to 12 carbon atoms; and Y is
selected from the group consisting of a single bond, an oxygen
atom, a sulfur atom and a group of formula: >N--R.sup.5, wherein
R.sup.5 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, straight or branched chain aliphatic acyl groups having from
1 to 8 carbon atoms and aromatic acyl groups having from 7 to 11
carbon atoms, a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof, with the proviso that
the amidocarboxylic acid derivative does not include compounds
wherein: R.sup.1 is selected from the group consisting of hydrogen
atoms, straight or branched chain alkyl groups having from 1 to 6
carbon atoms and aralkyl groups having from 7 to 12 carbon atoms
which include a straight or branched chain alkyl group having 1 to
4 carbon atoms substituted with an aryl moiety; R.sup.2 is selected
from the group consisting of straight or branched chain alkylene
groups having from 1 to 6 carbon atoms; R.sup.3 is selected from
the group consisting of (i) hydrogen atoms, (ii) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii)
straight or branched chain dialkylamino groups in which each of
said alkyl groups are the same or different and each has from 1 to
4 carbon atoms, (viii) aryl
groups having from 6 to 10 carbon atoms which are unsubstituted or
have from 1 to 5 substituents selected from substituents .alpha.'
defined below, (ix) aralkyl groups having from 7 to 12 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below on said aryl moiety, (x)
hydroxyl groups and (xi) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is selected
from the group consisting of straight or branched chain alkylene
group having from 1 to 6 carbon atoms; W is selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms
which are unsubstituted or have from 1 to 5 substituents selected
from substituents .alpha.' defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which are unsubstituted or have from 1 to
5 substituents selected from substituents .alpha.' defined below on
said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon
atoms which include a straight or branched chain alkyl group having
1 to 4 carbon atoms substituted with an aryl moiety which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which are
unsubstituted or have from 1 to 5 substituents selected from
substituents .alpha.' defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which are unsubstituted or have
from 1 to 5 substituents selected from substituents .alpha.'
defined below and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xii) pyridyl, (xiii)
quinolyl, (xiv) amino groups, (xv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, and (xvi) straight or branched chain dialkylamino
groups in which each of said alkyl moieties may be the same or
different and each has from 1 to 4 carbon atoms, X is a phenyl
group which is unsubstituted or has 1 to 3 substituents .alpha.'
defined below or a hetero aryl group selected from the group
consisting of pyridyl, quinolyl and isoquinolyl, said hetero aryl
group being unsubstituted or having from 1 to 3 substituents
selected from substituents .alpha.' defined below; said
substituents .alpha.' are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which are unsubstituted or have
from 1 to 3 substituents selected from substituents .beta.' defined
below, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which said alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms, (xviii) straight or branched chain dialkylamino
groups in which said alkyl moieties are the same or different and
each has from 1 to 4 carbon atoms, (xix) a phenyl group which is
unsubstituted or has 1 to 3 substituents .beta.' defined below and
(xx) a hetero aryl group selected from the group consisting of
pyridyl, quinolyl and isoquinolyl, said hetero aryl group being
unsubstituted or having from 1 to 3 substituents .beta.' defined
below; said substituents .beta.' are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen
atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups,
(xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which said alkyl moieties are the same or different and each has
from 1 to 4 carbon atoms, (xvi) straight or branched chain
aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups which are the same or
different and each has from 1 to 4 carbon atoms and said alkyl
moiety is a straight or branched chain alkyl group having from 1 to
4 carbon atoms, and (xix) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms; and Y is selected from the group consisting of a
single bond, an oxygen atom, a sulfur atom and a group of formula:
>N--R.sup.5 wherein R.sup.5 is selected from the group
consisting of hydrogen atoms, straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, and straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms.
122. A method for the therapy or prevention of a disease in a warm
blooded animal according to claim 121, wherein said warm blooded
animal is a human.
123. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms.
124. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms.
125. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom.
126. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.2 is a straight or branched chain alkylene group having from
2 to 4 carbon atoms.
127. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.2 is an ethylene group.
128. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms, alkoxy groups having one or two carbon atoms, alkylthio
groups having one or two carbon atoms, halogen atoms, nitro groups,
hydroxyl groups and straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms.
129. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is selected from the group consisting of hydrogen atoms,
halogen atoms and nitro groups.
130. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.3 is a hydrogen atom.
131. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms.
132. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is selected from the group consisting of hydrogen atoms and
methyl groups.
133. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.4 is a hydrogen atom.
134. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms.
135. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Z
is a methylene group.
136. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below, (vi)
aryloxy groups having from 6 to 10 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below on said aryl
moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.1 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety
(the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms), (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms.
137. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl
groups, (iii) straight or branched chain alkoxy groups having from
1 to 4 carbon atoms, (iv) straight or branched chain alkylthio
groups having from 1 to 4 carbon atoms, (v) aryl groups having from
6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below, (vi)
aryloxy groups having from 6 to 10 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.2
defined below on said aryl moiety, (vii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.2 defined below on said aryl
moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl group in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms.
138. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
(iii) aryloxy groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (iv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 defined below
on said aryl moiety, (v) aralkyl groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (vi)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vii) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero aryloxy
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(ix) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.3 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
139. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
(iii) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .alpha..sup.4 defined below on said
phenyl moiety, (iv) phenylthio groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.4 defined below on said phenyl moiety, (v)
aralkyl groups having from 7 to 10 carbon atoms, (vi) aralkyloxy
groups having from 7 to 10 carbon atoms, (vii) aryloxyalkyl groups
in which said aryl moiety has from 6 to 10 carbon atoms and said
alkyl moiety is straight or branched chain and has from 1 to 4
carbon atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero
aryloxy groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (ix) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.4 are selected from the
group consisting (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having one or two carbon atoms,
(vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups.
140. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of phenoxy groups which may
have one substituent selected from substituents .alpha..sup.5
defined below on said phenyl moiety; said substituents
.alpha..sup.5 are selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or
branched chain halogenated alkoxy groups having from 1 to 4 carbon
atoms, (v) straight or branched chain alkylthio groups having one
or two carbon atoms, (vi) straight or branched chain alkylsulfonyl
groups having from one or two carbon atoms, (vii) halogen atoms,
(viii) cyano groups and (ix) pyridyl groups.
141. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: W
is selected from the group consisting of phenoxy groups which may
have one substituent selected from substituents .alpha..sup.6
defined below on said phenyl moiety; said substituents
.alpha..sup.6 are selected from the group consisting of methyl,
ethyl, isopropyl, t-butyl, trifluoromethyl, methoxy and
trifluoromethoxy groups, and fluorine atoms and chlorine atoms.
142. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.7 defined below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined
below; said substituents .alpha..sup.7 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (xiv) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (xv) phenyl groups which
may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvi) phenoxy groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xvii) phenylthio groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xviii) phenylsulfonyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atom, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms.
143. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.8 described below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups, the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms.
144. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of aryl groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.9 described below and mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined
below; said substituents .alpha..sup.9 are selected from the group
consisting of (i) hydroxyl groups, (ii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, (iii) straight or
branched chain halogenated alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
145. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of phenyl, indolyl, pyridyl
and quinolyl groups, which may have from 1 to 3 substituents
selected from substituents .alpha..sup.11 defined below; said
substituents .alpha..sup.11 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.7 described
below, (vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.7 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.7 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.7 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms.
146. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of phenyl groups which may
have one substituent selected from substituents .alpha..sup.12
defined below; said substituents .alpha..sup.12 are selected from
the group consisting of methyl, isopropyl and hydroxyl groups,
fluorine atoms, chlorine atoms, diethylamino and benzyl groups,
phenyl groups, said phenyl groups may be substituted with 1 to 3
substituents, which may be the same or different, selected from the
group consisting of methyl, ethyl, trifluoromethyl, hydroxyl,
methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups, phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino, N-methylphenylsulfonylamino and pyridyl
groups, said pyridyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms, and nitro, dimethylamino
and diethylamino groups, pyridyloxy, pyridylthio, pyridylsulfonyl
and piperidyl groups; or X is selected from the group consisting of
pyridyl groups which may have one substituent selected from
substituents .alpha..sup.13 defined below; said substituents
.alpha..sup.13 are selected from the group consisting of methyl,
isopropyl, methoxy, ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropox-
y and benzyloxy groups, alkylthio groups having one or two carbon
atoms, alkylsulfonyl groups having one or two carbon atoms. benzyl
groups, phenyl groups (said phenyl groups may be substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups), phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino
and N-methylphenylsulfonylamino groups.
147. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: X
is selected from the group consisting of biphenylyl groups, each
phenyl moiety may be substituted with one substituent, which may be
the same or different, selected from the group consisting of
methyl, trifluoromethyl, hydroxyl, methoxy and hydroxymethyl
groups, fluorine atoms, chlorine atoms. and formyl, carboxyl,
nitro, dimethylamino and N,N-dimethylaminomethyl groups, a
pyridylphenyl group, said pyridyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups and phenylpyridyl groups,
said phenyl moiety may be substituted with one substituent selected
from the group consisting of methyl, ethyl, trifluoromethyl,
methoxy, ethoxy and isopropoxy groups, fluorine atoms, chlorine
atoms, and nitro and dimethylamino group.
148. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Y
is selected from the group consisting of a single bond and an
oxygen atom.
149. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein: Y
is an oxygen atom.
150. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, straight or branched chain alkyl groups having from
1 to 4 carbon atoms, alkoxy groups having one or two carbon atoms,
alkylthio groups having one or two carbon atoms, halogen atoms,
nitro groups, hydroxyl groups and straight or branched chain
aliphatic acyl groups having from 1 to 5 carbon atoms; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 4 carbon atoms; Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms (ii) hydroxyl groups, (iii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iv) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (v) aryl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined
below, (vi) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (x) aralkylthio groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.1 defined below on said aryl
moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.1 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .alpha..sup.1
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano
groups, (xv) amino groups (xvi) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which said alkoxy moiety has from 1 to 4 carbon atoms,
(xviii) aralkyloxycarbonylamino groups in which said aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (xxiv)
arylsulfonyl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below on said aryl moiety, (xxv) arylsulfonylamino groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xxvi) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .beta..sup.1 defined below, (xxvii)
mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxviii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxix) mono- or dicyclic, 5- to 10-membered hetero arylsulfonyl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxx) mono- or dicyclic, 5- to
10-membered hetero arylsulfonylamino groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said hetero aryl moiety, the nitrogen atom of said amino moiety
may be substituted with a straight or branched chain alkyl group
having from 1 to 6 carbon atoms rand (xxxi) mono- or dicyclic, 5-
to 10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.1
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) amino groups, (xiv) straight or
branched chain monoalkylamino groups in which said alkyl moiety has
from 1 to 4 carbon atoms, (xv) straight or branched chain
dialkylamino groups in which each of said alkyl moieties may be the
same or different and each has from 1 to 4 carbon atoms, (xvi)
straight or branched chain aminoalkyl groups having from 1 to 4
carbon atoms, (xvii) monoalkylaminoalkyl groups in which said
monoalkylamino moiety has one straight or branched chain alkyl
group having from 1 to 4 carbon atoms and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xviii) dialkylaminoalkyl groups in which said dialkylamino
moiety has two straight or branched chain alkyl groups having from
1 to 4 carbon atoms which may be the same or different and said
alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (xix) straight or branched chain
alkoxycarbonylamino groups in which said alkoxy moiety has from 1
to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in which
said aryl moiety has from 6 to 10 carbon atoms and said alkyl
moiety has from 1 to 4 carbon atoms; X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.7 defined below; said
substituents .alpha..sup.7 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain aliphatic acyl
groups having from 1 to 5 carbon atoms, (vi) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (viii) straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(x) straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (xi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (xiv) aralkyl groups having from 7 to 12 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xv) phenyl groups which may have from
1 to 3 substituents selected from substituents .beta..sup.3 defined
below, (xvi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xvii)
phenylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xviii)
phenylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xix)
phenylsulfonylamino groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below on said
phenyl moiety, the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
151. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, halogen atoms and nitro groups; R.sup.4 is selected
from the group consisting of hydrogen atoms and straight or
branched chain alkyl groups having from 1 to 4 carbon atoms; Z is a
methylene group; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) hydroxyl groups, (iii) straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms (iv) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(v) aryl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.2
defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (vii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (viii) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents a defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to o 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups (the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms) and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
152. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms,
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms and aralkyl groups having from 7 to 9 carbon atoms; R.sup.2
is a straight or branched chain alkylene group having from 2 to 4
carbon atoms; R.sup.3 is selected from the group consisting of
hydrogen atoms, halogen atoms and nitro groups; R.sup.4 is selected
from the group consisting of hydrogen atoms and straight or
branched chain alkyl groups having from 1 to 4 carbon atoms; Z is a
methylene group; W is selected from the group consisting of (i)
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms, (ii) straight or branched chain alkoxy groups having from 1
to 4 carbon atoms, (iii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 described below on the aryl moiety, (iv)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (v) aralkyl groups having from 7
to 12 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.3 defined below on said aryl moiety,
(vi) aralkyloxy groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.3 defined below on said aryl moiety, (vii) aryloxyalkyl
groups in which said aryl moiety is an aryl group having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.3 defined below and said alkyl moiety
is a straight or branched chain alkyl group having from 1 to 4
carbon atoms, (viii) mono- or dicyclic, 5- to 10-membered hetero
aryloxy groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (ix) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.9 defined below
and mono- or dicyclic 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below; said substituents .alpha..sup.9 are
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.5 defined below, (vi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.5 defined
below, (vii) pyridyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
153. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom; R.sup.2 is an ethylene group; R.sup.3
is a hydrogen atom; R.sup.4 is a hydrogen atom; Z is a methylene
group; W is a phenoxy group which may have one substituent selected
from substituents .alpha..sup.5 defined below on said phenyl
moiety; said substituents .alpha..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
alkylthio groups having one or two carbon atoms, (vi) straight or
branched chain alkylsulfonyl groups having from one or two carbon
atoms, (vii) halogen atoms, (viii) cyano groups and (ix) pyridyl
groups; X is selected from the group consisting of phenyl groups
which may have one substituent selected from substituents
.alpha..sup.12 defined below; said substituents .alpha..sup.12 are
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups (said phenyl groups may be substituted
with 1 to 3 substituents, which may be the same or different,
selected from the group consisting of methyl, ethyl,
trifluoromethyl, hydroxyl, methoxy, ethoxy, isopropoxy,
trifluoromethoxy, methylenedioxy and hydroxymethyl groups, fluorine
atoms, chlorine atoms, and nitro, formyl, cyano, carboxyl,
dimethylamino, diethylamino and N,N-dimethylaminomethyl groups),
phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino,
N-methylphenylsulfonylami- no and pyridyl groups (said pyridyl
groups may be substituted with a substituent selected from the
group consisting of methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms, and nitro, dimethylamino and diethylamino groups),
pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl groups; or X
is selected from the group consisting of pyridyl groups which may
have one substituent selected from substituents .alpha..sup.13
defined below; said substituents .alpha..sup.13 are selected from
the group consisting of methyl, isopropyl, methoxy, ethoxy,
isopropoxy, 2,2,3,3-tetrafluoropropoxy and benzyloxy groups,
alkylthio groups having one or two carbon atoms, alkylsulfonyl
groups having one or two carbon atoms, benzyl groups, phenyl
groups, said phenyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups, phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino and
N-methylphenylsulfonylamino groups; and Y is an oxygen atom.
154. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is a hydrogen atom; R.sup.2 is an ethylene group; R.sup.3
is a hydrogen atom; R.sup.4 is a hydrogen atom; Z is a methylene
group; W is a phenoxy group which may have one substituent selected
from substituents .alpha..sup.6 defined below on said phenyl
moiety; said substituents .alpha..sup.6 are selected from the group
consisting of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl,
methoxy and trifluoromethoxy groups, and fluorine atoms and
chlorine atoms; X is a biphenylyl group, the substituents of each
phenyl moiety may be the same or different and they are selected
from the group consisting of methyl, trifluoromethyl, hydroxyl,
methoxy and hydroxymethyl groups, fluorine atoms, chlorine atoms,
and formyl, carboxyl, nitro, dimethylamino and
N,N-dimethylaminomethyl groups, a pyridylphenyl group, said pyridyl
moiety may be substituted with one substituent selected from the
group consisting of methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms and nitro, dimethylamino and diethylamino groups and
phenylpyridyl groups, said phenyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy and isopropoxy groups,
fluorine atoms, chlorine atoms, and nitro and dimethylamino
groups); and Y is an oxygen atom.
155. A method for therapy or prevention according to claim 122,
wherein said active ingredient is an amidocarboxylic acid
derivative of formula (I), a pharmacologically acceptable salt
thereof or a pharmacologically acceptable ester thereof, wherein:
R.sup.1 is selected from the group consisting of hydrogen atoms and
straight or branched chain alkyl groups having from 1 to 6 carbon
atoms; R.sup.2 is a straight or branched chain alkylene group
having from 1 to 6 carbon atoms; R.sup.3 is selected from the group
consisting of (i) hydrogen atoms, (ii) straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, (iii) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight
or branched chain dialkylamino groups in which each alkyl group may
be the same or different and have from 1 to 4 carbon atoms, (viii)
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents .alpha. defined below and (ix) aralkyl groups
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha. defined below on said aryl moiety; R.sup.4 is
selected from the group consisting of hydrogen atoms and straight
or branched chain alkyl groups having from 1 to 6 carbon atoms; Z
is a straight or branched chain alkylene group having from 1 to 4
carbon atoms; W is selected from the group consisting of ethyl,
propyl, butyl, pentyl, methoxy, ethoxy, propoxy, isopropoxy,
methylthio, ethylthio, propylthio, isopropylthio, phenoxy,
4-methylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy,
4-methoxyphenoxy, 4-chlorophenoxy, phenylthio, benzyl, phenethyl,
3-phenylpropyl and 4-phenylbutyl groups; X is selected from the
group consisting of aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below and mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .alpha. defined below; said substituents .alpha. are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms (ii) straight or
branched chain halogenated alkyl groups having from 1 to 4 carbon
atoms, (iii) hydroxyl groups, (iv) straight or branched chain
aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain alkylenedioxy groups having
from 1 to 4 carbon atoms, (vii) aralkyloxy groups having from 7 to
12 carbon atoms, (viii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (ix) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (x) halogen
atoms, (xi) nitro groups, (xii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (xiii) aralkyl groups
having from 7 to 12 carbon atoms, (xiv) aryl groups having from 6
to 10 carbon atoms (said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms), (xv)
aryloxy groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvi) arylthio groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xvii) arylsulfonyl groups
having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (xviii) arylsulfonylamino groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, and the nitrogen atom of
said amino moiety may be substituted with a straight or branched
chain alkyl group having from 1 to 6 carbon atoms), (xix) mono- or
dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xx) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xxi) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, (xxii) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom and (xxiii) mono- or dicyclic, 5-
to 10-membered hetero arylsulfonylamino groups containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, the nitrogen atom of said
amino moiety may be substituted with a straight or branched chain
alkyl group having from 1 to 6 carbon atoms; and Y is selected from
the group consisting of a single bond, an oxygen atom, a sulfur
atom and groups of formula: >N--R.sup.5, wherein R.sup.5 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain aliphatic acyl groups having from 1 to 8
carbon atoms and aromatic acyl groups having from 7 to 11 carbon
atoms.
156. A method for therapy or prevention according to claim 122,
wherein said disease is selected from the group consisting of
diabetes mellitus, impaired glucose tolerance, insulin-resistant
non-IGT, gestational diabetes mellitus and hyperlipemia.
157. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus.
158. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms, alkoxy
groups having one or two carbon atoms, alkylthio groups having one
or two carbon atoms, halogen atoms, nitro groups, hydroxyl groups
and straight or branched chain aliphatic acyl groups having from 1
to 5 carbon atoms; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a straight or branched chain
alkylene group having from 1 to 4 carbon atoms; W is selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (vii) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety,
(viii) aralkyl groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .alpha..sup.1 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below; said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups, the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety, the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms and (xxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
159. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (vii) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety,
(viii) aralkyl groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .alpha..sup.8 defined
below; said substituents .alpha..sup.8 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
straight or branched chain dialkylamino groups in which each alkyl
group may be the same or different and each has from 1 to 4 carbon
atoms, (x) phenyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.4 defined below, (xi) phenoxy
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xii) phenylthio groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xiii) furyl groups, (xiv) thienyl
groups, (xv) oxazolyl groups, (xvi) isoxazolyl groups, (xvii)
thiazolyl groups, (xviii) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xix) imidazolyl groups (the nitrogen atom of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms) and (xx) mono- or dicyclic,
5- to 10-membered saturated heterocyclic groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom; said substituents
.beta..sup.4 are selected from the group consisting (i) straight or
branched chain alkyl groups having from 1 to 6 carbon atoms, (ii)
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and Y is an oxygen atom.
160. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iii) aryloxy
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 described
below on the aryl moiety, (iv) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (v)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vi) aralkyloxy groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.3 defined below on said aryl
moiety, (vii) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.3 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (viii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.3
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups; X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.9 defined below; said
substituents .alpha..sup.9 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
161. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.5 defined below on said phenyl moiety; said
substituents .alpha..sup.5 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (v) straight or branched chain alkylthio groups
having one or two carbon atoms, (vi) straight or branched chain
alkylsulfonyl groups having from one or two carbon atoms, (vii)
halogen atoms, (viii) cyano groups and (ix) pyridyl groups; X is
selected from the group consisting of phenyl groups which may have
one substituent selected from substituents .alpha..sup.12 defined
below; said substituents .alpha..sup.12 are selected from the group
consisting of methyl, isopropyl and hydroxyl groups, fluorine
atoms, chlorine atoms, diethylamino and benzyl groups, phenyl
groups, said phenyl groups may be substituted with 1 to 3
substituents, which may be the same or different, selected from the
group consisting of methyl, ethyl, trifluoromethyl, hydroxyl,
methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups, phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino, N-methylphenylsulfonylamino and pyridyl groups
(said pyridyl groups may be substituted with a substituent selected
from the group consisting of methyl, ethyl, trifluoromethyl,
methoxy, ethoxy, isopropoxy and trifluoromethoxy groups, fluorine
atoms, chlorine atoms, and nitro, dimethylamino and diethylamino
groups), pyridyloxy, pyridylthio, pyridylsulfonyl and piperidyl
groups; or X is selected from the group consisting of pyridyl
groups which may have one substituent selected from substituents
.alpha..sup.13 defined below; said substituents .alpha..sup.13 are
selected from the group consisting of methyl, isopropyl, methoxy,
ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropox- y and benzyloxy
groups, alkylthio groups having one or two carbon atoms,
alkylsulfonyl groups having one or two carbon atoms, benzyl groups,
phenyl groups (said phenyl groups may be substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups), phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino
and N-methylphenylsulfonylamino groups; and Y is an oxygen
atom.
162. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.6 defined below on said phenyl moiety; said
substituents .alpha..sup.are selected from the group consisting of
methyl, ethyl, isopropyl, t-butyl, trifluoromethyl, methoxy and
trifluoromethoxy groups, and fluorine atoms and chlorine atoms; X
is a biphenylyl group, the substituents of each phenyl moiety may
be the same or different and they are selected from the group
consisting of methyl, trifluoromethyl, hydroxyl, methoxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and formyl,
carboxyl, nitro, dimethylamino and N,N-dimethylaminomethyl groups),
a pyridylphenyl group, said pyridyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups and phenylpyridyl groups
(said phenyl moiety may be substituted with one substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms, and nitro and dimethylamino groups; and Y is
an oxygen atom.
163. A method for therapy or prevention according to claim 122,
wherein said disease is diabetes mellitus and said active
ingredient is an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 6 carbon atoms; R.sup.2 is a straight
or branched chain alkylene group having from 1 to 6 carbon atoms;
R.sup.3 is selected from the group consisting of (i) hydrogen
atoms, (ii) straight or branched chain alkyl groups having from 1
to 6 carbon atoms, (iii) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (viii) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha. defined below and (ix) aralkyl groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
.alpha. defined below on said aryl moiety; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is a straight
or branched chain alkylene group having from 1 to 4 carbon atoms; W
is selected from the group consisting of ethyl, propyl, butyl,
pentyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio,
ethylthio, propylthio, isopropylthio, phenoxy, 4-methylphenoxy,
4-ethylphenoxy, 4-isopropylphenoxy, 4-methoxyphenoxy,
4-chlorophenoxy, phenylthio, benzyl, phenethyl, 3-phenylpropyl and
4-phenylbutyl groups; X is selected from the group consisting of
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha. defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below; said substituents .alpha. are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (vii) aralkyloxy groups having from 7 to 12 carbon atoms,
(viii) straight or branched chain alkylthio groups having from 1 to
4 carbon atoms, (ix) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (x) halogen atoms, (xi)
nitro groups, (xii) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and have
from 1 to 4 carbon atoms, (xiii) aralkyl groups having from 7 to 12
carbon atoms, (xiv) aryl groups having from 6 to 10 carbon atoms,
said aryl moiety may be substituted with a substituent selected
from the group consisting of straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
halogen atoms and straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (xv) aryloxy groups having from 6
to 10 carbon atoms, said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms, (xvi)
arylthio groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvii) arylsulfonyl groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xviii) arylsulfonylamino
groups having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, and the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xix) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xx) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxi) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonyl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xxiii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonylamino groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms; and Y is selected from the group
consisting of a single bond, an oxygen atom, a sulfur atom and
groups of formula: >N--R.sup.5, wherein R.sup.5 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms and
aromatic acyl groups having from 7 to 11 carbon atoms.
164. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia.
165. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, straight or
branched chain alkyl groups having from 1 to 4 carbon atoms, alkoxy
groups having one or two carbon atoms, alkylthio groups having one
or two carbon atoms, halogen atoms, nitro groups, hydroxyl groups
and straight or branched chain aliphatic acyl groups having from 1
to 5 carbon atoms; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a straight or branched chain
alkylene group having from 1 to 4 carbon atoms; W is selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents as defined below, (vi) aryloxy groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .alpha..sup.1 defined below on said aryl moiety,
(vii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.1 defined below on said aryl moiety, (viii) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.1 defined below
on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below on said aryl moiety, (x)
aralkylthio groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .alpha..sup.1
defined below on said aryl moiety, (xi) aryloxyalkyl groups in
which said aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.1 defined below and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom and
(xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .alpha..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents selected from substituents .beta..sup.1
defined below, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which
said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which said alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which said aralkyl moiety has
from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each of said alkyl groups may be the
same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .beta..sup.1 defined
below on said aryl moiety, (xxi) aryl groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1, which may be the same or different,
defined below, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.1 defined below on said aryl moiety,
(xxiii) arylthio groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said aryl moiety, (xxiv) arylsulfonyl
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below
on said aryl moiety, (xxv) arylsulfonylamino groups having from 6
to 10 carbon atoms which may have from 1 to 3 substituents selected
from substituents .beta..sup.1 defined below on said aryl moiety,
the nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxvii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below, (xxix) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.1 defined below,
(xx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.1 defined below on said hetero aryl moiety, the nitrogen
atom of said amino moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms and
(xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.1 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) amino groups, (xiv) straight or branched chain
monoalkylamino groups in which said alkyl moiety has from 1 to 4
carbon atoms, (xv) straight or branched chain dialkylamino groups
in which each of said alkyl moieties may be the same or different
and each has from 1 to 4 carbon atoms, (xvi) straight or branched
chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii)
monoalkylaminoalkyl groups in which said monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which said dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and said alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which said aryl moiety has from 6
to 10 carbon atoms and said alkyl moiety has from 1 to 4 carbon
atoms; X is selected from the group consisting of aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.7 defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha..sup.7 defined below; said substituents .alpha..sup.7 are
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below, (x) straight or branched
chain alkylthio groups having from 1 to 4 carbon atoms, (xi)
straight or branched chain alkylsulfonyl groups having from 1 to 4
carbon atoms, (xii) halogen atoms, (xiii) straight or branched
chain dialkylamino groups in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xiv) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xv) phenyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xvi) phenoxy groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.3 defined below, (xvii) phenylthio groups which may have
from 1 to 3 substituents selected from substituents .beta..sup.3
defined below, (xviii) phenylsulfonyl groups which may have from 1
to 3 substituents selected from substituents .beta..sup.3 defined
below, (xix) phenylsulfonylamino groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below
on said phenyl moiety (the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), (xx) furyl groups, (xxi) thienyl groups,
(xxii) oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.3 defined below,
(xxvi) pyridyloxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxvii)
pyridylthio groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.3 defined below, (xxviii)
pyridylsulfonyl groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.3 defined below, (xxix)
imidazolyl groups (the nitrogen atom of the ring of said imidazolyl
groups may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.3 defined below on said pyridyl moiety (the
nitrogen atom of said amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms) and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom; said substituents .beta..sup.3 are selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) straight or branched chain hydroxyalkyl groups
having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix) nitro
groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is selected from
the group consisting of a single bond and an oxygen atom.
166. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iv) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below, (vi) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (vii) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety,
(viii) aralkyl groups having from 7 to 12 carbon atoms which may
have from 1 to 3 substituents selected from substituents
.alpha..sup.2 defined below on said aryl moiety, (ix) aralkyloxy
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
on said aryl moiety, (x) aralkylthio groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.2 defined below on said aryl moiety, (xi)
aryloxyalkyl groups in which said aryl moiety is an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.2 defined below
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (xiii) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
of said alkyl moieties may be the same or different and each has
from 1 to 4 carbon atoms, (xiii) aryl groups having from 6 to 10
carbon atoms which may be the same or different and which have from
1 to 3 substituents selected from substituents .beta..sup.2 defined
below, (xiv) aryloxy groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below on said aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below
on said aryl moiety, (xvi) mono- or dicyclic, 5- to 10-membered
hetero aryl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents selected from
substituents .beta..sup.2 defined below, (xvii) mono- or dicyclic,
5- to 10-membered hetero aryloxy groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents .beta..sup.2 defined below,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.beta..sup.2 defined below and (xix) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom; said substituents .beta..sup.2
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each of said alkyl moieties may be the same or different and
each has from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups
in which said dialkylamino moiety has two straight or branched
chain alkyl groups having from 1 to 4 carbon atoms which may be the
same or different and said alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; X is selected
from the group consisting of aryl groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.8 defined below and mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom which may have from 1 to 3
substituents selected from substituents as defined below; said
substituents .alpha..sup.8 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv)
straight or branched chain aliphatic acyloxy groups having from 1
to 5 carbon atoms, (v) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (vi) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (vii)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (viii) halogen atoms, (ix) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (x) phenyl groups
which may have from 1 to 3 substituents selected from substituents
.beta..sup.4 defined below, (xi) phenoxy groups which may have from
1 to 3 substituents selected from substituents .beta..sup.4 defined
below, (xii) phenylthio groups which may have from 1 to 3
substituents selected from substituents .beta..sup.4 defined below,
(xiii) furyl groups, (xiv) thienyl groups, (xv) oxazolyl groups,
(xvi) isoxazolyl groups, (xvii) thiazolyl groups, (xviii) pyridyl
groups which may have from 1 to 3 substituents selected from
substituents .beta..sup.4 defined below, (xix) imidazolyl groups
(the nitrogen atom of said imidazolyl groups may be substituted
with a straight or branched chain alkyl group having from 1 to 6
carbon atoms) and (xx) mono- or dicyclic, 5- to 10-membered
saturated heterocyclic groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom; said substituents .beta..sup.4 are selected
from the group consisting (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
(iii) hydroxyl groups, (iv) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (v) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(vi) straight or branched chain alkylenedioxy groups having from 1
to 4 carbon atoms, (vii) straight or branched chain hydroxyalkyl
groups having from 1 to 4 carbon atoms, (viii) halogen atoms, (ix)
nitro groups, (x) formyl groups, (xi) cyano groups, (xii) carboxyl
groups, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (xiv) dialkylaminoalkyl groups in
which said dialkylamino moiety has two straight or branched chain
alkyl groups having from 1 to 4 carbon atoms which may be the same
or different and said alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms; and Y is an oxygen
atom.
167. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 4 carbon atoms and aralkyl groups
having from 7 to 9 carbon atoms; R.sup.2 is a straight or branched
chain alkylene group having from 2 to 4 carbon atoms; R.sup.3 is
selected from the group consisting of hydrogen atoms, halogen atoms
and nitro groups; R.sup.4 is selected from the group consisting of
hydrogen atoms and straight or branched chain alkyl groups having
from 1 to 4 carbon atoms; Z is a methylene group; W is selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iii) aryloxy
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents selected from substituents .alpha..sup.3 described
below on the aryl moiety, (iv) arylthio groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents selected from
substituents .alpha..sup.3 defined below on said aryl moiety, (v)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents selected from substituents .alpha..sup.3
defined below on said aryl moiety, (vi) aralkyloxy groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
selected from substituents .alpha..sup.3 defined below on said aryl
moiety, (vii) aryloxyalkyl groups in which said aryl moiety is an
aryl group having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha..sup.3 defined
below and said alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, (viii) mono- or dicyclic, 5-
to 10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom and (ix) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom; said substituents .alpha..sup.3
are selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups; X is selected from the group
consisting of aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents selected from substituents
.alpha..sup.9 defined below and mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
selected from substituents .alpha..sup.9 defined below; said
substituents .alpha..sup.9 are selected from the group consisting
of (i) hydroxyl groups, (ii) straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain halogenated alkoxy groups having from 1 to 4 carbon atoms,
(iv) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (v) phenyl groups which may have from 1 to 3
substituents selected from substituents .beta..sup.5 defined below,
(vi) phenoxy groups which may have from 1 to 3 substituents
selected from substituents .beta..sup.5 defined below, (vii)
pyridyl groups which may have from 1 to 3 substituents selected
from substituents .beta..sup.5 defined below and (viii) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
said substituents .beta..sup.5 are selected from the group
consisting of (i) straight or branched chain alkyl groups having
from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (v) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (vi) halogen
atoms, (vii) nitro groups, (viii) formyl groups, (ix) carboxyl
groups, (x) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms and (xi) dialkylaminoalkyl groups in which said
dialkylamino moiety has two straight or branched chain alkyl groups
having from 1 to 4 carbon atoms which may be the same or different
and said alkyl moiety is a straight or branched chain alkyl group
having from 1 to 4 carbon atoms; and Y is an oxygen atom.
168. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.5 defined below on said phenyl moiety; said
substituents .alpha..sup.5 are selected from the group consisting
of (i) straight or branched chain alkyl groups having from 1 to 6
carbon atoms, (ii) straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, (iii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (v) straight or branched chain alkylthio groups
having one or two carbon atoms, (vi) straight or branched chain
alkylsulfonyl groups having from one or two carbon atoms, (vii)
halogen atoms, (viii) cyano groups and (ix) pyridyl groups; X is
selected from the group consisting of phenyl groups which may have
one substituent selected from substituents .alpha..sup.12 defined
below; said substituents .alpha..sup.12 are selected from the group
consisting of methyl, isopropyl and hydroxyl groups, fluorine
atoms, chlorine atoms, diethylamino and benzyl groups, phenyl
groups, said phenyl groups may be substituted with 1 to 3
substituents, which may be the same or different, selected from the
group consisting of methyl, ethyl, trifluoromethyl, hydroxyl,
methoxy, ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups, phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino, N-methylphenylsulfonylamino and pyridyl
groups, said pyridyl groups may be substituted with a substituent
selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy, isopropoxy and trifluoromethoxy
groups, fluorine atoms, chlorine atoms, and nitro, dimethylamino
and diethylamino groups, pyridyloxy, pyridylthio, pyridylsulfonyl
and piperidyl groups; or X is selected from the group consisting of
pyridyl groups which may have one substituent selected from
substituents .alpha..sup.13 defined below; said substituents
.alpha..sup.13 are selected from the group consisting of methyl,
isopropyl, methoxy, ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropox-
y and benzyloxy groups, alkylthio groups having one or two carbon
atoms, alkylsulfonyl groups having one or two carbon atoms, benzyl
groups, phenyl groups (said phenyl groups may be substituted with a
substituent selected from the group consisting of methyl, ethyl,
trifluoromethyl, methoxy, ethoxy and isopropoxy groups, fluorine
atoms, chlorine atoms and nitro, dimethylamino and diethylamino
groups), phenoxy, phenylthio, phenylsufonyl, phenylsulfonylamino
and N-methylphenylsulfonylamino groups; and Y is an oxygen
atom.
169. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is a hydrogen atom;
R.sup.2 is an ethylene group; R.sup.3 is a hydrogen atom; R.sup.4
is a hydrogen atom; Z is a methylene group; W is a phenoxy group
which may have one substituent selected from substituents
.alpha..sup.6 defined below on said phenyl moiety; said
substituents .alpha..sup.6 are selected from the group consisting
of methyl, ethyl, isopropyl, t-butyl, trifluoromethyl, methoxy and
trifluoromethoxy groups, and fluorine atoms and chlorine atoms; X
is a biphenylyl group, the substituents of each phenyl moiety may
be the same or different and they are selected from the group
consisting of methyl, trifluoromethyl, hydroxyl, methoxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, and formyl,
carboxyl, nitro, dimethylamino and N,N-dimethylaminomethyl groups,
a pyridylphenyl group, said pyridyl moiety may be substituted with
one substituent selected from the group consisting of methyl,
ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy and
trifluoromethoxy groups, fluorine atoms, chlorine atoms and nitro,
dimethylamino and diethylamino groups and phenylpyridyl groups,
said phenyl moiety may be substituted with one substituent selected
from the group consisting of methyl, ethyl, trifluoromethyl,
methoxy, ethoxy and isopropoxy groups, fluorine atoms, chlorine
atoms, and nitro and dimethylamino groups; and Y is an oxygen
atom.
170. A method for therapy or prevention according to claim 122,
wherein said disease is hyperlipemia and said active ingredient is
an amidocarboxylic acid derivative of formula (I), a
pharmacologically acceptable salt thereof or a pharmacologically
acceptable ester thereof, wherein: R.sup.1 is selected from the
group consisting of hydrogen atoms and straight or branched chain
alkyl groups having from 1 to 6 carbon atoms; R.sup.2 is a straight
or branched chain alkylene group having from 1 to 6 carbon atoms;
R.sup.3 is selected from the group consisting of (i) hydrogen
atoms, (ii) straight or branched chain alkyl groups having from 1
to 6 carbon atoms, (iii) straight or branched chain alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (viii) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha. defined below and (ix) aralkyl groups having
from 7 to 12 carbon atoms which may have from 1 to 3 substituents
.alpha. defined below on said aryl moiety; R.sup.4 is selected from
the group consisting of hydrogen atoms and straight or branched
chain alkyl groups having from 1 to 6 carbon atoms; Z is a straight
or branched chain alkylene group having from 1 to 4 carbon atoms; W
is selected from the group consisting of ethyl, propyl, butyl,
pentyl, methoxy, ethoxy, propoxy, isopropoxy, methylthio,
ethylthio, propylthio, isopropylthio, phenoxy, 4-methylphenoxy,
4-ethylphenoxy, 4-isopropylphenoxy, 4-methoxyphenoxy,
4-chlorophenoxy, phenylthio, benzyl, phenethyl, 3-phenylpropyl and
4-phenylbutyl groups; X is selected from the group consisting of
aryl groups having from 6 to 10 carbon atoms which may have from 1
to 3 substituents selected from substituents .alpha. defined below
and mono- or dicyclic, 5- to 10-membered hetero aryl groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom
which may have from 1 to 3 substituents selected from substituents
.alpha. defined below; said substituents .alpha. are selected from
the group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (vi) straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, (vii) aralkyloxy groups having from 7 to 12 carbon atoms,
(viii) straight or branched chain alkylthio groups having from 1 to
4 carbon atoms, (ix) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (x) halogen atoms, (xi)
nitro groups, (xii) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and have
from 1 to 4 carbon atoms, (xiii) aralkyl groups having from 7 to 12
carbon atoms, (xiv) aryl groups having from 6 to 10 carbon atoms
(said aryl moiety may be substituted with a substituent selected
from the group consisting of straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, straight
or branched chain alkoxy groups having from 1 to 4 carbon atoms,
halogen atoms and straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (xv) aryloxy groups having from 6
to 10 carbon atoms, said aryl moiety may be substituted with a
substituent selected from the group consisting of straight or
branched chain alkyl groups having from 1 to 6 carbon atoms,
straight or branched chain halogenated alkyl groups having from 1
to 4 carbon atoms, straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, halogen atoms and straight or branched
chain alkylenedioxy groups having from 1 to 4 carbon atoms, (xvi)
arylthio groups having from 6 to 10 carbon atoms, said aryl moiety
may be substituted with a substituent selected from the group
consisting of straight or branched chain alkyl groups having from 1
to 6 carbon atoms, straight or branched chain halogenated alkyl
groups having from 1 to 4 carbon atoms, straight or branched chain
alkoxy groups having from 1 to 4 carbon atoms, halogen atoms and
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (xvii) arylsulfonyl groups having from 6 to 10 carbon
atoms, said aryl moiety may be substituted with a substituent
selected from the group consisting of straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, halogen atoms and straight or branched chain alkylenedioxy
groups having from 1 to 4 carbon atoms, (xviii) arylsulfonylamino
groups having from 6 to 10 carbon atoms, said aryl moiety may be
substituted with a substituent selected from the group consisting
of straight or branched chain alkyl groups having from 1 to 6
carbon atoms, straight or branched chain halogenated alkyl groups
having from 1 to 4 carbon atoms, straight or branched chain alkoxy
groups having from 1 to 4 carbon atoms, halogen atoms and straight
or branched chain alkylenedioxy groups having from 1 to 4 carbon
atoms, and the nitrogen atom of said amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, (xix) mono- or dicyclic, 5- to
10-membered hetero aryl groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, (xx) mono- or dicyclic, 5- to 10-membered
hetero aryloxy groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxi) mono- or dicyclic, 5- to 10-membered hetero
arylthio groups containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom, (xxii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonyl groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom and (xxiii) mono- or dicyclic, 5- to 10-membered hetero
arylsulfonylamino groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the nitrogen atom of said amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms; and Y is selected from the group
consisting of a single bond, an oxygen atom, a sulfur atom and
groups of formula: >N--R.sup.5, wherein R.sup.5 is selected from
the group consisting of hydrogen atoms, straight or branched chain
alkyl groups having from 1 to 6 carbon atoms, straight or branched
chain aliphatic acyl groups having from 1 to 8 carbon atoms and
aromatic acyl groups having from 7 to 11 carbon atoms.
171. A method for therapy or prevention according to claim 122,
wherein said disease is obesity.
172. A method for therapy or prevention according to claim 122,
wherein said disease is impaired glucose tolerance.
173. A method for therapy or prevention according to claim 122,
wherein said disease is insulin-resistant non-IGT.
174. A method for therapy or prevention according to claim 122,
wherein said disease is fatty liver.
175. A method for therapy or prevention according to claim 122,
wherein said disease is a diabetic complication.
176. A method for therapy or prevention according to claim 122,
wherein said disease is arteriosclerosis.
177. A method for therapy or prevention according to claim 122,
wherein said disease is gestational diabetes mellitus.
178. A method for therapy or prevention according to claim 122,
wherein said disease is polycystic ovary syndrome.
179. A method for therapy or prevention according to claim 122,
wherein said disease is atherosclerosis.
180. A method for therapy or prevention according to claim 122,
wherein said disease is arthrosteitis.
181. A method for therapy or prevention according to claim 122,
wherein said disease is rheumatic arthritis.
182. A method for therapy or prevention according to claim 122,
wherein said disease is an allergic disease.
183. A method for therapy or prevention according to claim 122,
wherein said disease is asthma.
184. A method for therapy or prevention according to claim 122,
wherein said disease is cancer.
185. A method for therapy or prevention according to claim 122,
wherein said disease is an autoimmune disease.
186. A method for therapy or prevention according to claim 122,
wherein said disease is pancreatitis.
187. A method for therapy or prevention according to claim 122,
wherein said disease is cataracts.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional application of application
Ser. No. 09/540,765 filed Mar. 30, 2000, which is a
continuation-in-part application of International Application
PCT/JP98/04396, filed Sep. 30, 1998.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to amidocarboxylic acid
derivatives, or their pharmacologically acceptable salts or their
pharmacologically acceptable esters. These compounds have some
excellent effects of lowering blood glucose, reducing lipid,
ameliorating insulin resistance, alleviating inflammatory diseases,
immunoregulation, inhibiting aldose reductase, inhibiting
5-lipoxygenase, suppressing generation of lipid peroxide,
activating PPAR (peroxysome proliferator activated receptor) and
alleviating osteoporosis.
[0004] Furthermore, the present invention relates to a composition
containing the above-mentioned amidocarboxylic acid derivatives,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof as an active ingredient useful in the
treatment and prevention of the following diseases. They include
diseases caused mainly by insulin resistance such as diabetes
mellitus, hyperlipemia, obesity, impaired glucose tolerance (IGT),
insulin resistant non-IGT (NGT), hypertension, fatty liver,
diabetic complications (for example, retinopathy, nephropathy,
neurosis, cataracts, coronary artery diseases, etc.),
arteriosclerosis, gestational diabetes mellitus (GDM), polycystic
ovary syndrome (PCOS) and cell injury caused by atherosclerosis
(for example cerebral injury induced by apoplexy and the like);
inflammatory diseases such as arthrosteitis, pain, pyrexia,
rheumatic arthritis, inflammatory enteritis, acne, sunburn,
psoriasis, eczema, allergic diseases, asthma, GI ulcers, cancer,
cachexia, autoimmune diseases and pancreatitis; osteoporosis;
cataracts; etc. The present invention relates to a use of these
compounds, their salts and esters for producing a medicament for
prevention or treatment of these diseases, or a method of treating
or preventing these diseases by administration of pharmacologically
effective amounts of such compounds to warm-blooded animals.
[0005] 2. Background Information
[0006] While insulin and sulfonylurea compounds such as tolbutamide
and Glipizide have conventionally been used as therapeutic agents
for diabetes mellitus and hyperglycemia, and carboxylic acid
derivatives have recently been reported to be useful
insulin-nondependent diabetes therapeutic agents. These compounds
are described, for example in:
[0007] (1-1) International Patent Publication No. WO91/19702
(Japanese PCT Application (Kokai) No. Hei 5-507920);
[0008] (1-2) International Patent Publication WO94/29285;
[0009] (1-3) International Patent Publication WO94/29302;
[0010] (1-4) International Patent Publication WO95/03288; and
[0011] (1-5) International Patent Publication WO96/04260.
[0012] However, the compounds described above are different from
the compounds of the present invention to be described later in
that the former compounds do not have the characteristics of the
latter compounds which have an amide bond in the side chain of the
carboxylic acid derivative.
[0013] Compounds having amide bonds in the side chains are
described, for example in:
[0014] (2-1) Japanese Patent Application (Kokai) No. Hei
6-172339;
[0015] (2-2) International Patent Publication WO92/07850 (=Japanese
PCT Application (Kokai) No. Hei 6-502144); and
[0016] (2-3) U.S. Pat. No. 5,330,998.
[0017] However, these compounds are different from the compounds of
the present invention to be described later in that the former
compounds have thiazolidyl groups and the like at the terminal of
the molecule.
[0018] Although carboxylic acid derivatives having amide bonds in
the side chains are described, for example, in:
[0019] (3-1) Japanese Patent Application (Kokai) No. Hei 5-155828;
and
[0020] (3-2) Japanese Patent Application (Kokai) No. Hei 5-279353,
the compound (3-1) and the compound (3-2) are different from the
present invention in pharmacological activity and chemical
structure. The compound (3-1) has an effect of inhibiting
aggregation and in the molecule of the compound (3-1) there is an
amino group or the like at the 2- to 5-positions of the carboxylic
acid and a heterocyclic group or the like at the terminal of the
side chain. The compound (3-2) has an inhibitory action against
damage of ischemic tissue and is an acetic acid derivative.
SUMMARY OF THE INVENTION
[0021] The present inventors made intensive studies on
amidocarboxylic acid derivatives, and pharmacologically acceptable
salts and esters thereof, which have strong effects of lowering
blood glucose, reducing lipid, ameliorating insulin resistance,
alleviating inflammatory diseases, immunoregulation, inhibiting
aldose reductase. inhibiting 5-lipoxygenase, suppressing generation
of lipid peroxide, activating PPAR (peroxysome proliferator
activated receptor) and alleviating osteoporosis, and accomplished
the present invention.
[0022] To describe it in detail, the present invention provides
novel amidocarboxylic acid derivatives, pharmacologically
acceptable salts thereof and pharmacologically acceptable esters
thereof which are useful as therapeutic or preventive agents for
diseases caused mainly by insulin resistance such as diabetes
mellirus, hyperlipemia, obesity, impaired glucose tolerance,
insulin resistant non-IGT, hypertension, fatty liver, diabetic
complications (e.g., retinopathy, nephropathy, neurosis, cataracts,
coronary artery diseases, etc.), arteriosclerosis, gestational
diabetes mellitus, polycystic ovary syndrome and cell injury caused
by atherosclerosis (for example, cerebral injury induced by
apoplexy and the like); inflammatory diseases such as
arthrosteitis, pain, pyrexia, rheumatic arthritis, inflammatory
enteritis, acne, sunburn, psoriasis, eczema, allergic diseases,
asthma, GI ulcers, cancer, cachexia, autoimmune diseases (e.g.
systemic lupus erythematosus, juvenile rheumatoid arthritis,
Sjogren's syndrome, diffuse scleroderma, mixed connective tissue
disease, dermatomyositis, Hashimoto's disease, primary myxoma,
thyrotoxia, pernicious anemia, ulcerative colitis, autoimmune
atrophic gastritis, idiopathic Addison disease, male sterility,
Goodpasture's syndrome, acute progressive glomerulonephritis,
myasthenia gravis, polymyositis, pemphigus vulgaris, bullous
pemphigoid, sympathetic ophthalmitis, multiple sclerosis,
autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura,
rheumatic fever, lupoid hepatitis, primary biliary cirrhosis,
Behcet's disease, CREST syndrome, etc.) and pancreatitis;
osteoporosis; and cataracts.
[0023] Further, the present invention provides (i) pharmaceutical
compositions containing as an active ingredient the novel
amidocarboxylic acid derivatives, the pharmacologically acceptable
salts thereof or the pharmacologically acceptable esters thereof
and (ii) methods of treating by administering said active
ingredient to a warm blooded animal, and particularly to a
human.
[0024] The present invention relates to an amidocarboxylic acid
derivative of the formula (I): 2
[0025] a pharmacologically acceptable salt thereof or a
pharmacologically acceptable ester thereof.
[0026] In the formula,
[0027] R.sup.1 represents a hydrogen atom, a straight or branched
chain alkyl group having from 1 to 6 carbon atoms or an aralkyl
group having from 7 to 12 carbon atoms;
[0028] R.sup.2 represents a straight or branched chain alkylene
group having from 1 to 6 carbon atoms;
[0029] R.sup.3 represents (i) a hydrogen atom, (ii) a straight or
branched chain alkyl group having from 1 to 6 carbon atoms, (iii) a
straight or branched chain alkoxy group having from 1 to 4 carbon
atoms, (iv) a straight or branched chain alkylthio group having
from 1 to 4 carbon atoms, (v) a halogen atom, (vi) a nitro group,
(vii) a straight or branched chain dialkylamino group in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (viii) an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents .alpha. described later,
(ix) an aralkyl group having from 7 to 12 carbon atoms which may
have from 1 to 5 substituents .alpha. described later on the aryl
moiety, (x) a hydroxyl group or (xi) a straight or branched chain
aliphatic acyl group having from 1 to 5 carbon atoms;
[0030] R.sup.4 represents a hydrogen atom or a straight or branched
chain alkyl group having from 1 to 6 carbon atoms;
[0031] Z represents a straight or branched chain alkylene group
having from 1 to 6 carbon atoms;
[0032] W represents (i) a straight or branched chain alkyl group
having from 1 to 6 carbon atoms, (ii) a hydroxyl group, (iii) a
straight or branched chain alkoxy group having from 1 to 4 carbon
atoms, (iv) a straight or branched chain alkylthio group having
from 1 to 4 carbon atoms, (v) an aryl group having from 6 to 10
carbon atoms which may have from 1 to 5 substituents .alpha.
described later, (vi) an aryloxy group having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents .alpha. described
later on the aryl moiety, (vii) an arylthio group having from 6 to
10 carbon atoms which may have from 1 to 5 substituents .alpha.
described later on the aryl moiety, (viii) an aralkyl group having
from 7 to 12 carbon atoms which may have from 1 to 5 substituents
.alpha. described later on the aryl moiety, (ix) an aralkyloxy
group having from 7 to 12 carbon atoms which may have from 1 to 5
substituents .alpha. described later on the aryl moiety, (x) an
aralkylthio group having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents .alpha. described later on the aryl
moiety, (xi) an aryloxyalkyl group in which the aryl moiety has
from 6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha. described later and the alkyl moiety is a straight or
branched chain alkyl having from 1 to 4 carbon atoms, (xii) a mono-
or dicyclic, 5- to 10-membered hetero aryl group containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiii) a mono- or
dicyclic, 5- to 10-membered hetero aryloxy group containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, a nitrogen atom and a sulfur atom, (xiv) a mono- or dicyclic,
5- to 10-membered hetero arylthio group containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xv) a mono- or dicyclic, 5- to
10-membered saturated heterocyclic group containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom, (xvi) an amino group, (xvii) a
straight or branched chain monoalkylamino group in which the alkyl
moiety has from 1 to 4 carbon atoms, (xviii) a straight or branched
chain dialkylamino group in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, (xix) an
N-alkyl-N-arylamino group having a straight or branched chain alkyl
group having from 1 to 4 carbon atoms and an aryl group having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha., (xx) an arylamino group having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents .alpha. described later on
the aryl moiety, (xxi) an aralkylamino group having from 7 to 12
carbon atoms which may have from 1 to 5 substituents .alpha.
described later on the aryl moiety or (xxii) an aralkyloxycarbonyl
amino group having an aralkyl group having from 7 to 12 carbon
atoms which may have from 1 to 5 substituents .alpha. described
later on the aryl moiety;
[0033] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha. described later or
a mono- or dicyclic, 5- to 10-membered hetero aryl group having
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, a nitrogen atom and a sulfur atom which may have from
1 to 3 substituents .alpha. described later, when W represents (1)
a straight or branched chain alkyl group having from 1 to 6 carbon
atoms, (2) a hydroxyl group, (3) a straight or branched chain
alkoxy group having from 1 to 4 carbon atoms, (4) a straight or
branched chain alkylthio group having from 1 to 4 carbon atoms, (5)
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 5 substituents .alpha. described later, (6) an aryloxy group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents .alpha. described later on the aryl moiety, (7) an
arylthio group having from 6 to 10 carbon atoms which may have from
1 to 5 substituents .alpha. described on the aryl moiety, (8) an
aralkyl group having from 7 to 12 carbon atoms which may have from
1 to 5 substituents .alpha. described later on the aryl moiety, (9)
an aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents .alpha. described later on the aryl
moiety, (10) an aralkylthio group having from 7 to 12 carbon atoms
which may have from 1 to 5 substituents .alpha. described later on
the aryl moiety, (11) an aryloxyalkyl group in which the aryl
moiety is an aryl group having from 6 to 10 carbon atoms which may
have from 1 to 5 substituents .alpha. described later and the alkyl
moiety is a straight or branched chain alkyl having from 1 to 4
carbon atoms, (12) a mono- or dicyclic, 5- to 10-membered hetero
aryl group containing from 1 to 4 hetero atoms selected from the
group consisting of an oxygen atom, a nitrogen atom and a sulfur
atom, (13) a mono- or dicyclic, 5- to 10-membered hetero aryloxy
group containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
(14) a mono- or dicyclic, 5- to 10-membered hetero arylthio group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom or
(15) a mono- or dicyclic, 5- to 10-membered saturated heterocyclic
group containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, a nitrogen atom and a sulfur atom,
or
[0034] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha. described later
when W represents (1) an amino group, (2) a straight or branched
chain monoalkylamino group in which the alkyl moiety has from 1 to
4 carbon atoms, (3) a straight or branched chain dialkylamino group
in which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (4) an N-alkyl-N-arylamino group having a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms and an aryl group having from 6 to 10 carbon atoms which may
have from 1 to 5 substituents .alpha., (5) an arylamino group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents .alpha. described later on the aryl moiety, (6) an
aralkyl amino group having from 7 to 12 carbon atoms which may have
from 1 to 5 substituents .alpha. described later on the aryl moiety
or (7) an aralkyloxycarbonylamino group having an aralkyl group
having from 7 to 12 carbon atoms which may have from 1 to 5
substituents .alpha. described later on the aryl moiety,
[0035] The above substituent a represents a group selected from the
group consisting of (i) straight or branched chain alkyl groups
having from 1 to 6 carbon atoms, (ii) straight or branched chain
halogenated alkyl groups having from 1 to 4 carbon atoms, (iii)
hydroxylgroups, (iv) straight or branched chain aliphatic acyloxy
groups having from 1 to 5 carbon atoms, (v) straight or branched
chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (viii) straight or branched chain
alkylenedioxy groups having from 1 to 4 carbon atoms, (ix)
aralkyloxy groups having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .beta. described later, (x) straight or
branched chain alkylthio groups having from 1 to 4 carbon atoms,
(xi) straight or branched chain alkylsulfonyl groups having from 1
to 4 carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv)
cyano groups, (xv) amino groups, (xvi) straight or branched chain
monoalkylamino groups in which the alkyl moiety has from 1 to 4
carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino
groups in which the alkoxy moiety has from 1 to 4 carbon atoms,
(xiii) aralkyloxycarbonylamino groups in which the aralkyl moiety
has from 7 to 12 carbon atoms, (xix) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (xx) aralkyl
groups having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .beta. described later on the aryl moiety, (xxi) aryl
groups having from 6 to 10 carbon atoms and which may have from 1
to 3 substituents .beta., which may be the same or different,
described later, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .beta. described
later on the aryl moiety, (xxiii) arylthio groups having from 6 to
10 carbon atoms which may have from 1 to 3 substituents .beta.
described later on the aryl moiety, (xxiv) arylsulfonyl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta. described later on the aryl moiety, (xxv)
arylsulfonylamino groups having from 6 to 10 carbon atoms which may
have from 1 to 3 substituents .beta. described later on the aryl
moiety (the nitrogen atom of the amino moiety may be substituted
with a straight or branched chain alkyl group having from 1 to 6
carbon atoms), (xxvi) a mono- or dicyclic, 5- to 10-membered hetero
aryl group containing from 1 to 4 hetero atoms selected from the
group consisting of an oxygen atom, a nitrogen atom and a sulfur
atom which may have from 1 to 3 substituents .beta. described
later, (xxvii) a mono- or dicyclic, 5- to 10-membered hetero
aryloxy group containing from 1 to 4 hetero atoms selected from the
group consisting of an oxygen atom, a nitrogen atom and a sulfur
atom which may have from 1 to 3 substituents .beta. described
later, (xxviii) a mono- or dicyclic, 5- to 10-membered hetero
arylthio group containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom which may have from 1 to 3 substituents .beta.
described later, (xxix) a mono- or dicyclic, 5- to 10-membered
hetero arylsulfonyl group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
.beta. described later, (xxx) a mono- or dicyclic, 5- to
10-membered hetero arylsulfonylamino group containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
a nitrogen atom and a sulfur atom which may have from 1 to 3
substituents .beta. described later on the hetero aryl moiety (the
nitrogen atom of the amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms) and (xxxi) a mono- or dicyclic, 5- to 10-membered saturated
heterocyclic group containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom;
[0036] The above substituent .beta. represents (i) a straight or
branched chain alkyl group having from 1 to 6 carbon atoms, (ii) a
straight or branched chain halogenated alkyl group having from 1 to
4 carbon atoms, (iii) a hydroxyl group, (iv) a straight or branched
chain alkoxy group having from 1 to 4 carbon atoms, (v) a straight
or branched chain halogenated alkoxy group having from 1 to 4
carbon atoms, (vi) a straight or branched chain alkylenedioxy group
having from 1 to 4 carbon atoms, (vii) a straight or branched chain
hydroxyalkyl group having from 1 to 4 carbon atoms, (viii) a
straight or branched chain aliphatic acyl group having from 1 to 5
carbon atoms, (ix) a halogen atom, (x) a nitro group, (xi) a cyano
group, (xii) a carboxyl group, (xiii) an amino group, (xiv) a
straight or branched chain monoalkylamino group in which the alkyl
moiety has from 1 to 4 carbon atoms, (xv) a straight or branched
chain dialkylamino group in which each alkyl moiety may be the same
or different and each has from 1 to 4 carbon atoms, (xvi) a
straight or branched chain aminoalkyl group having from 1 to 4
carbon atoms, (xvii) a monoalkylaminoalkyl group in which the
monoalkylamino moiety has one straight or branched chain alkyl
group having from 1 to 4 carbon atoms and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xviii) a dialkylaminoalkyl group in which the dialkylamino
moiety has two straight or branched chain alkyl groups which may be
the same or different and each has from 1 to 4 carbon atoms and the
alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (xix) a straight or branched chain
alkoxycarbonylamino group in which the alkoxy moiety has from 1 to
4 carbon atoms or (xx) an aralkyloxycarbonylamino group in which
the aralkyl moiety has from 7 to 12 carbon atoms; and
[0037] Y represents a single bond, an oxygen atom, a sulfur atom or
a group of the formula: >N--R.sup.5 (wherein R.sup.5 represents
a hydrogen atom, a straight or branched chain alkyl group having
from 1 to 6 carbon atoms, a straight or branched chain aliphatic
acyl group having from 1 to 8 carbon atoms or an aromatic acyl
group having from 7 to 11 carbon atoms).
DETAILED DESCRIPTION OF THE INVENTION
[0038] In the case where R.sup.1, R.sup.3, R.sup.4, R.sup.5 or W
represent a straight or branched chain alkyl group having from 1 to
6 carbon atoms, the alkyl group includes, for example, a methyl,
ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl,
pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl,
1,1-diethylpropyl, 1,2-diethylpropyl, 2,2-dimethylpropyl,
1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl,
3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl,
1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl,
2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl,
2-ethylbutyl, 1,1,2-trimethylpropyl or 1,2,2-trimethylpropyl group;
preferably, each of R.sup.1, R.sup.3, R.sup.4 and R.sup.5 is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, and W is a straight or branched chain alkyl group having
from 2 to 6 carbon atoms; more preferably, each of R.sup.1,
R.sup.3, R.sup.4 and R.sup.5 is a methyl, ethyl, propyl, isopropyl,
butyl or isobutyl group, and W is an ethyl, propyl, isopropyl,
butyl, isobutyl or pentyl group. Most preferably, each of R.sup.1
and R.sup.5 is an alkyl group having one or two carbon atoms
(particularly a methyl group), R.sup.3 is a methyl, ethyl or
isopropyl group (particularly a methyl or isopropyl group), R.sup.4
is an alkyl group having one or two carbon atoms (particularly a
methyl group), and W is a propyl, butyl or pentyl group
(particularly a propyl or butyl group).
[0039] In the case where R.sup.1 represents an aralkyl group having
from 7 to 12 carbon atoms, the aralkyl group is a group in which a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms is substituted with an aryl group and includes, for example,
a benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl,
6-phenylhexyl, 1-naphthylmethyl or 2-naphthylmethyl group,
preferably a benzyl, phenethyl or 3-phenylpropyl-group, more
preferably a 3-phenylpropyl group.
[0040] In the case where R.sup.2 or Z represent a straight or
branched chain alkylene group having from 1 to 6 carbon atoms, the
alkylene group includes, for example, a methylene, ethylene,
methylethylene, ethylethylene, 1,1-dimethylethylene,
1,2-dimethylethylene, trimethylene, 1-methyltrimethylene,
1-ethyltrimethylene, 2-methyltrimethylene,
1,1-dimethyltrimethylene, tetramethylene, pentamethylene or
hexamethylene group, preferably R.sup.2 is a straight or branched
chain alkylene group having from 2 to 5 carbon atoms, more
preferably R.sup.2 is a straight or branched chain alkylene group
having from 2 to 4 carbon atoms, still more preferably R.sup.2 is
an ethylene, trimethylene or methylethylene group, most preferably
R.sup.2 is an ethylene group. Preferably, Z is a straight or
branched chain alkylene group having from 1 to 4 carbon atoms (for
example, a methylene, ethylene, methylethylene, ethylethylene,
trimethylene, 1-methyltrimethylene or 2-methyltrimethylene group),
more preferably an alkylene group having one or two carbon atoms,
most preferably a methylene group.
[0041] In the case where R.sup.3 or W represents a straight or
branched chain alkoxy group having from 1 to 4 carbon atoms, the
alkoxy group includes, for example, a methoxy, ethoxy, propoxy,
isopropoxy, butoxy, s-butoxy, t-butoxy or isobutoxy group;
preferably R.sup.3 is an alkoxy group having from 1 to 3 carbon
atoms (particularly methoxy, ethoxy or isopropoxy group); more
preferably an alkoxy group having one or two carbon atoms
(particularly a methoxy group). Preferably, W is an alkoxy group
having from 1 to 3 carbon atoms, more preferably an ethoxy
group.
[0042] In the case where R.sup.3 or W represents a straight or
branched chain alkylthio group having from 1 to 4 carbon atoms, the
alkylthio group includes, for example, methylthio, ethylthio,
propylthio, isopropylthio, butylthio, s-butylthio, t-butylthio or
isobutylthio group; preferably R.sup.3 is an alkylthio group having
one or two carbon atoms; more preferably a methylthio group. W is
preferably an alkylthio group having from 1 to 3 carbon atoms (for
example, a methylthio, ethylthio, propylthio or
isopropylthiogroup); more preferably a methylthio group.
[0043] In the case where R.sup.3 represents a halogen atom, the
halogen atom includes a fluorine atom, a chlorine atom, a bromine
atom or an iodine atom; preferably a fluorine atom, a chlorine atom
or a bromine atom; more preferably a fluorine atom or a chlorine
atom.
[0044] In the case where R.sup.3 or W represents a straight or
branched chain dialkylamino group in which each alkyl group may be
the same or different and each has from 1 to 4 carbon atoms, the
dialkylamino group includes, for example, a dimethylamino,
diethylamino, dipropylamino, diisopropylamino, dibutylamino,
N-methyl-N-ethylamino or N-ethyl-N-isopropylamino group; preferably
a dimethylamino or diethylamino group; more preferably a
diethylamino group.
[0045] In the case where R.sup.3 or W represents an aryl group
having from 6 to 10 carbon atoms which may have from 1 to 5
substituents .alpha. described later, the unsubstituted aryl group
includes, for example, phenyl or naphthyl group, preferably a
phenyl group. The substituted aryl group includes, for example, a
methylphenyl, ethylphenyl, propylphenyl, isopropylphenyl,
trifluoromethylphenyl, hydroxyphenyl, acetylphenyl, methoxyphenyl,
methylenedioxyphenyl, benzyloxyphenyl, methylthiophenyl,
methanesulfonylphenyl, fluorophenyl, difluorophenyl, chlorophenyl,
dichlorophenyl, nitrophenyl, (dimethylamino)phenyl, benzylphenyl,
biphenylyl, phenoxyphenyl, phenylthiophenyl, phenylsulfonylphenyl,
(phenylsulfonylamino)phenyl, pyridylphenyl, pyridyloxyphenyl,
pyridylthiophenyl, (pyridylsulfonylamino)phenyl, methylnaphthyl,
trifluoronaphthyl, hydroxynaphthyl, methoxynaphthyl,
fluoronaphthyl, chloronaphthyl or pyridylnaphthyl group; preferably
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha. described later; more preferably a
methylphenyl, ethylphenyl, isopropylphenyl, methoxyphenyl,
methylthiophenyl or chlorophenyl group.
[0046] In the case where R.sup.3 or W represents an aralkyl group
having from 7 to 12 carbon atoms which may have from 1 to 5
substituents .alpha. described later on the aryl moiety, the
aralkyl group is a group in which the straight or branched chain
alkyl group having from 1 to 4 carbon atoms is substituted with the
above aryl group and includes, for example, a benzyl, phenethyl,
3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl,
naphthylmethyl, methylbenzyl, trifluoromethylbenzyl, methoxybenzyl,
methylenedioxybenzyl, methylthiobenzyl, methanesulfonylbenzyl,
fluorobenzyl, chlorobenzyl, 2-(methylphenyl)ethyl,
2-(methoxyphenyl)ethyl, 3-(methylphenyl)propyl,
3-(methoxyphenyl)propyl, 4-(methylphenyl)butyl or
4-(methoxyphenyl)butyl group; preferably R.sup.3 is a benzyl or
phenethyl group; most preferably a benzyl group. W is preferably an
aralkyl group having from 7 to 12 carbon atoms which may have from
1 to 3 substituents .alpha. described later on the aryl moiety;
more preferably an aralkyl group having from 7 to 10 carbon atoms
(for example, a benzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl
group); most preferably a 3-phenylpropyl or 4-phenylbutyl group
(particularly the 3-phenylpropyl group).
[0047] In the case where R.sup.3 represents a straight or branched
chain aliphatic acyl group having from 1 to 5 carbon atoms, the
aliphatic acyl group includes, for example, a formyl, acetyl,
propionyl, butyryl, isobutyryl, pentanoyl or pivaloyl group,
preferably a formyl, acetyl or pivaloyl group; most preferably a
formyl or acetyl group.
[0048] In the case where W represents an aryloxy group having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha. described later on the aryl moiety, the unsubstituted
aryloxy group includes, for example, a phenoxy or naphthyloxy
group; preferably a phenoxy group. The substituted aryloxy group
includes, for example, a methylphenoxy, ethylphenoxy,
propylphenoxy, isopropylphenoxy, t-butylphenoxy,
trifluoromethylphenoxy, methoxyphenoxy, ethoxyphenoxy,
isopropoxyphenoxy, trifluoromethoxyphenoxy, methylthiophenoxy,
ethylthiophenoxy, cyanophenoxy, formylphenoxy, fluorophenoxy,
difluorophenoxy, trifluorophenoxy, pentafluorophenoxy,
chlorophenoxy, dichlorophenoxy, trichlorophenoxy, pyridylphenoxy,
biphenylyloxy, methanesulfonylphenoxy, methylnaphthyloxy,
ethylnaphthyloxy, propylnaphthyloxy, isopropylnaphthyloxy,
t-butylnaphthyloxy, trifluoromethylnaphthyloxy, methoxynaphthyloxy,
ethoxynaphthyloxy, isopropoxynaphthyloxy,
trifluoromethoxynaphthyloxy, methylthionaphthyloxy,
ethylthionaphthyloxy, cyanonaphthyloxy, formylnaphthyloxy,
fluoronaphthyloxy, difluoronaphthyloxy, trifluoronaphthyloxy,
pentafluoronaphthyloxy, chloronaphthyloxy, dichloronaphthyloxy,
trichloronaphthyloxy, pyridylnaphthyloxy, biphenylyloxy or
methanesulfonylnaphthyloxy group; preferably an aryloxy group
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha. described later on the aryl moiety; more
preferably a phenoxy group which may have from 1 to 3 substituents
.alpha. described later on the phenyl moiety (particularly a
phenoxy group which may have one substituent .alpha. described
later on the phenyl moiety); most preferably a methylphenoxy,
ethylphenoxy, isopropylphenoxy, t-butylphenoxy,
trifluoromethylphenoxy, methoxyphenoxy, ethoxyphenoxy,
trifluoromethoxyphenoxy, cyanophenoxy, formylphenoxy,
fluorophenoxy, difluorophenoxy, trifluorophenoxy,
pentafluorophenoxy, chlorophenoxy, dichlorophenoxy,
trichlorophenoxy, pyridylphenoxy or methanesulfonylphenoxy group;
still most preferably a methylphenoxy, ethylphenoxy,
isopropylphenoxy, t-butylphenoxy, trifluoromethylphenoxy,
methoxyphenoxy, ethoxyphenoxy, trifluoromethoxyphenoxy,
cyanophenoxy, formylphenoxy, fluorophenoxy, difluorophenoxy,
trifluorophenoxy, pentafluorophenoxy, chlorophenoxy,
dichlorophenoxy, trichlorophenoxy or methanesulfonylphenoxy group;
particularly most preferably a 4-methylphenoxy, 4-isopropylphenoxy,
4-t-butylphenoxy, 4-methoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-fluorophenoxy, 4-fluorophenoxy or 4-chlorophenoxy group.
[0049] In the case where W represents an arylthio group having from
6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha. described later on the aryl moiety, the unsubstituted
arylthio group includes, for example, a phenylthio or naphthylthio
group; preferably a phenylthio group. The substituted arylthio
group includes, for example, a methylphenylthio, ethylphenylthio,
propylphenylthio, isopropylphenylthio, methoxyphenylthio,
ethoxyphenylthio, methylthiophenylthio, ethylthiophenylthio,
biphenylylthio, 4-methanesulfonylphenylthio, methylnaphthylthio,
ethylnaphthylthio, propylnaphthylthio, isopropylnaphthylthio,
methoxynaphthylthio, ethoxynaphthylthio, methylthionaphthylthio,
ethylthionaphthylthio or 4-methanesulfonylnaphthy- lthio group;
preferably an arylthio group having 6 to 10 carbon atoms which may
have from 1 to 3 substituents .alpha. described later; more
preferably a phenylthio group which may have from 1 to 3
substituents .alpha. described later on the phenyl moiety; most
preferably a methylphenylthio, isopropylphenylthio or
methoxyphenylthio group.
[0050] In the case where W represents an aralkyloxy group having
from 7 to 12 carbon atoms which may have from 1 to 5 substituents
.alpha. described later on the aryl moiety, the unsubstituted
aralkyloxy group is a group in which the straight or branched chain
alkyloxy group having from 1 to 4 carbon atoms is substituted with
the above aryl group and includes, for example, a benzyloxy,
phenethyloxy, 3-phenylpropyloxy, 4-phenylbutyloxy,
1-naphthylmethyloxy or 2-naphthylmethyloxy group; preferably an
aralkyloxy group having from 7 to 10 carbon atoms; more preferably
a benzyloxy or phenethyloxy group (particularly a benzyloxy group).
The substituted aralkyloxy group includes, for example, a
methylbenzyloxy, methoxybenzyloxy, 2-(methylphenyl)ethoxy,
2-(methoxyphenyl)ethoxy, 3-(methylphenyl)propoxy,
3-(methoxyphenyl)propoxy, 4-(methylphenyl)butoxy or
4-(methoxyphenyl)butoxy group; preferably an aralkyloxy group
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha. described later on the aryl moiety; more
preferably a methylbenzyloxy or 2-(methylphenyl)ethoxy group.
[0051] In the case where W represents an aralkylthio group having
from 7 to 12 carbon atoms in the aryl moiety which may have from 1
to 5 substituents .alpha. described later, the unsubstituted
aralkylthio group is a group in which the straight or branched
chain alkylthio group having from 1 to 4 carbon atoms is
substituted with the above aryl group and includes, for example, a
benzylthio, phenethylthio, 3-phenylpropylthio, 4-phenylbutylthio,
1-naphthylmethylthio or 2-naphthylmethylthio group; preferably a
benzylthio or phenethylthio group; more preferably a benzylthio
group. The substituted aralkylthio group includes, for example, a
methylbenzylthio, methoxybenzylthio 2-(methylphenyl)ethylthio,
2-(methoxyphenyl)ethylthio, 3-(methylphenyl)propylthio,
3-(methoxyphenyl)propylthio, 4-(methylphenyl)butylthio or
4-(methoxyphenyl)butylthio group; preferably an aralkylthio group
having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha. described later in the aryl moiety; more
preferably a methylbenzylthio or 2-(methylphenyl)ethylthio
group.
[0052] In the case where W represents an aryloxyalkyl group in
which the aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 5 substituents .alpha. described
later and the alkyl moiety is a straight or branched chain alkyl
group having from 1 to 4 carbon atoms, the aryloxyalkyl group
includes, for example, a phenoxymethyl, 2-phenoxyethyl,
3-phenoxypropyl, 4-phenoxybutyl, naphthyloxymethyl,
2-naphthyloxyethyl, 3-naphthyloxypropyl or 4-naphthyloxybutyl
group; preferably an aryloxyalkyl group in which the aryl moiety is
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha. described later and the alkyl moiety is
a straight or branched chain alkyl group having from 1 to 4 carbon
atoms; more preferably an aryloxyalkyl group in which the aryl
moiety has from 6 to 10 carbon atoms and the alkyl moiety is a
straight or branched chain and has from 1 to 4 carbon atoms; still
more preferably a phenoxymethyl, 2-phenoxyethyl, 3-phenoxypropyl or
4-phenoxybutyl group; most preferably the 2-phenoxyethyl or
3-phenoxypropyl group particularly a 2-phenoxyethyl group).
[0053] In the case where W represents a mono- or dicyclic, 5- to
10-membered hetero aryl group containing 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the hetero aryl group includes, for
example, a furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl,
imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,
1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl,
pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolyl or
benzoxazolyl group: preferably a pyrrolyl, imidazolyl, furyl,
thienyl or pyridyl group; more preferably a pyrrolyl or imidazolyl
group.
[0054] In the case where W represents a mono- or dicyclic, 5- to
10-membered hetero aryloxy group containing 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the hetero aryloxy group includes, for
example, a furyloxy, thienyloxy, pyrrolyloxy, azepinyloxy,
pyrazolyloxy, imidazolyloxy, oxazolyloxy, isoxazolyloxy,
thiazolyloxy, isothiazolyloxy, 1,2,3-oxadiazolyloxy, triazolyloxy,
tetrazolyloxy, thiadiazolyloxy, pyranyloxy, pyridyloxy,
pyridazinyloxy, pyrimidinyloxy, pyrazinyloxy or benzoxazolyloxy
group; preferably a furyloxy, thienyloxy, pyrrolyloxy,
imidazolyloxy, thiazolyloxy or pyridyloxy group; more preferably a
pyridyloxy group.
[0055] In the case where W represents a mono- or dicyclic, 5- to
10-membered hetero arylthio group containing 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom, the hetero arylthio group includes, for
example, a furylthio, thienylthio, pyrrolylthio, azepinylthio,
pyrazolylthio, imidazolylthio, oxazolylthio, isoxazolylthio,
thiazolylthio, isothiazolylthio, 1,2,3-oxadiazolylthio,
triazolylthio, tetrazolylthio, thiadiazolylthio, pyranylthio,
pyridylthio, pyridazinylthio, pyrimidinylthio, pyrazinylthio or
benzoxazolylthio group; preferably a furylthio, thienylthio,
pyrrolylthio, imidazolylthio, thiazolylthio, pyridylthio or
benzoxazolylthio group; more preferably a benzoxazolylthio
group.
[0056] In the case where W represents a mono- or dicyclic, 5- to
10-membered saturated heterocyclic group containing 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom, a
nitrogen atom and a sulfur atom, the saturated heterocyclic group
includes, for example, morpholinyl, thiomorpholinyl, pyrrolidinyl,
pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl,
pyrazolinyl, piperidyl or piperazinyl group; preferably a
morpholinyl, thiomorpholinyl, pyrrolidinyl, imidazolinyl, piperidyl
or piperazinyl group.
[0057] In the case where W represents a straight or branched chain
monoalkylamino group in which the alkyl moiety has from 1 to 4
carbon atoms, the monoalkylamino group includes, for example, a
methylamino, ethylamino, propylamino, isopropylamino, butylamino,
s-butylamino, t-butylamino or isobutylamino group; preferably a
straight or branched chain monoalkylamino group having from 1 to 3
carbon atoms; more preferably a propylamino group.
[0058] In the case where W represents a N-alkyl-N-arylamino group
having a straight or branched chain alkyl group having from 1 to 4
carbon atoms and an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents .alpha. described later,
the alkyl moeity of the unsubstituted N-alkyl-N-arylamino group
includes, for example, a methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, s-butyl or t-butyl group; preferably a methyl, ethyl,
propyl, isopropyl, butyl or isobutyl group; more preferably a
methyl or ethyl group. The aryl moiety includes, for example, a
phenyl or naphthyl group; preferably a phenyl group. Specific
examples of the unsubstituted N-alkyl-N-arylamino group includes,
for example, a N-methyl-N-phenylamino, N-ethyl-N-phenylamino,
N-propyl-N-phenylamino, N-isopropyl-N-phenylamino,
N-butyl-N-phenylamino, N-isobutyl-N-phenylamino or
N-methyl-N-naphthylamino group; preferably a N-methyl-N-phenylamino
or N-ethyl-N-phenylamino group; more preferably a
N-ethyl-N-phenylamino group. The substituted N-alkyl-N-arylamino
group includes, for example, a N-methyl-N-(methylphenyl)amino,
N-ethyl-N-(methylphenyl)amino, N-methyl-N-(methoxyphenyl)amino or
N-ethyl-N-(methoxyphenyl)amino group; preferably a
N-methyl-N-(methylphenyl)amino or N-ethyl-N-(methylphenyl)amino
group.
[0059] In the case where W represents an arylamino group having
from 6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha. described later on the aryl moiety, the unsubstituted
arylamino group includes, for example, a phenylamino or
naphthylamino group; preferably a phenylamino group. The
substituted arylamino group includes, for example, a
(methylphenyl)amino, (ethylphenyl)amino, (propylphenyl)amino,
(isopropylphenyl)amino, (methoxyphenyl)amino, (ethoxyphenyl)amino,
(methylthiophenyl)amino, (ethylthiophenyl)amino, biphenylylamino or
(methanesulfonylphenyl)amino group; preferably a
(methylphenyl)amino, (isopropylphenyl)amino or (methoxyphenyl)amino
group.
[0060] In the case where W represents an aralkylamino group having
from 7 to 12 carbon atoms in the aralkyl moiety in which the aryl
moiety may have from 1 to 5 substituents .alpha. described later,
the unsubstituted aralkylamino group is a group in which a straight
or branched chain alkylamino group having from 1 to 4 carbon atoms
is substituted with the above aryl group and includes, for example,
a benzylamino phenethylamino, (3-phenylpropyl)amino,
(4-phenylbutyl)amino (1-naphthylmethyl)amino or
(2-naphthylmethyl)amino group; preferably a benzylamino or
phenethylamino group; more preferably a benzylamino group. The
substituted aralkylamino group includes, for example, a
(methylbenzyl)amino, (methoxybenzyl)amino,
[2-(methylphenyl)ethyl]amino, [2-(methoxyphenyl)ethyl]amino,
[3-(methylphenyl)propyl]amino, [3-(methoxyphenyl)propyl]amino,
[4-(methylphenyl)butyl]amino or [4-(methoxyphenyl)butyl]amino
group; preferably a (methylbenzyl)amino or
[2-(methylphenyl)ethyl]amino group.
[0061] In the case where W represents an aralkyloxycarbonylamino
group having an aralkyl moiety having from 7 to 12 carbon which may
have from 1 to 5 substituents .alpha. described later atoms on the
aryl moiety, the group includes, for example a benzyloxycarbonyl
group.
[0062] In the case where W represents an amino group, a straight or
branched chain monoalkylamino group in which the alkyl moiety has
from 1 to 4 carbon atoms, a straight or branched chain dialkylamino
group in which each alkyl moiety may be the same or different and
each has from 1 to 4 carbon atoms, a N-alkyl-N-arylamino group
having a straight or branched chain alkyl moiety having from 1 to 4
carbon atoms and an aryl moiety having from 6 to 10 carbon atoms
which may have from 1 to 5 substituents .alpha. described later, an
arylamino group having from 6 to 10 carbon atoms in the aryl moiety
which may have from 1 to 5 substituents .alpha. described later, or
an aralkylamino group having from 7 to 12 carbon atoms in the
aralkyl moiety in which the aryl moiety may have from 1 to 5
substituents .alpha. described later, W is preferably: an amino
group; a straight or branched chain monoalkylamino group in which
the alkyl moiety has from 1 to 4 carbon atoms; a straight or
branched chain dialkylamino group in which each alkyl group may be
the same or different and each has from 1 to 4 carbon atoms; a
N-alkyl-N-arylamino group having a straight or branched chain alkyl
moiety having from 1 to 4 carbon atoms and an aryl moeity having
from 6 to 10 carbon atoms which may have from 1 to 5 substituents
.alpha.; or an arylamino group having from 6 to 10 carbon atoms in
the aryl moiety which may have from 1 to 5 substituents .alpha.
described later.
[0063] In the case where R.sup.5 represents a straight or branched
chain aliphatic acyl group having from 1 to 8 carbon atoms or an
aromatic acyl group having from 7 to 11 carbon atoms, the acyl
group includes, for example, a formyl, acetyl, propionyl, butyryl,
pentanoyl, hexanoyl, heptanoyloctanoyl, benzoyl or p-toluoyl group;
preferably a straight or branched chain aliphatic acyl group having
from 1 to 8 carbon atoms; more preferably a straight or branched
chain aliphatic acyl group having from 2 to 5 carbon atoms; most
preferably an acetyl group.
[0064] In the case where X represents an aryl group having from 6
to 10 carbon atoms which may have from 1 to 3 substituents .alpha.
described later, the unsubstituted aryl group includes, for
example, a phenyl or naphthyl group, preferably a phenyl group. In
the case where X represents an aryl group which is substituted with
from 1 to 3 substituents .alpha. described later, the number of the
substituents is preferably one or two, more preferably one.
[0065] In the case where X represents a mono- or dicyclic, 5- to
10-membered hetero aryl group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, a nitrogen
atom and a sulfur atom which may have from 1 to 3 substituents
.alpha. described later, the unsubstituted hetero aryl group
comprises a monocyclic system or a dicyclic system. In the case of
the dicyclic system, one ring thereof at least is a heterocyclic
group. In the case of the dicyclic system, two rings are condensed
wherein one ring is a heterocycle and the other is a carbocycle, or
both rings are heterocycles. The heterocycle is a 5- or 6-membered
ring and contains from 1 to 4 hetero atoms selected from the group
consisting of a nitrogen atom, an oxygen atom and a sulfur atom.
The carbocycle is an aryl group having from 6 to 10 carbon atoms.
The monocyclic system is called a monocyclic hetero aryl group and
the dicyclic system is called a condensed hetero aryl group. In the
case of the ring having four hetero atoms, all of the four hetero
atoms are preferably nitrogen atoms and the number of hetero atoms
selected from the group consisting of an oxygen atom and a sulfur
atom is zero. In the case of the ring having three hetero atoms,
preferably three, two or one of the hetero atoms are nitrogen atoms
and one or two of the hetero atoms are those selected from the
group consisting of an oxygen and a sulfur atom. In the case of the
ring having two hetero atoms, preferably two, one or zero of the
hetero atoms are nitrogen atoms and zero one or two of the hetero
atoms are those selected from the group consisting of an oxygen
atom and a sulfur atom. In the case where X represents a hetero
aryl group substituted with from 1 to 3 substituents .alpha.
described later, the number of the substituents is preferably one
or two, more preferably one.
[0066] The unsubstituted monocyclic hetero aryl group includes, for
example, a pyrrolyl group such as a 2-pyrrolyl or 3-pyrrolyl group;
a furyl group such as a 2-furyl or 3-furyl group; a thienyl group
such as a 2-thienyl or 3-thienyl group; a pyridyl group such as a
2-pyridyl, 3-pyridyl or 4-pyridyl group; an imidazolyl group such
as a 2-imidazolyl or 4-imidazolyl group; a pyrazolyl group such as
a 3-pyrazolyl or 4-pyrazolyl group; an oxazolyl group such as a
2-oxazolyl, 4-oxazolyl or 5-oxazolyl group; an isoxazolyl group
such as a 3-isoxazolyl, 4-isoxazolyl or 5-isoxazolyl group; a
thiazolyl group such as a 2-thiazolyl, 4-thiazolyl or 5-thiazolyl
group; an isothiazolyl group such as a 3-isothiazolyl,
4-isothiazolyl or 5-isothiazolyl group; a triazolyl group such as a
1,2,3-triazol-4-yl, or 1,2,4-triazol-3-yl group; a thiadiazolyl
group such as a 1,3,4-thiadiazol-2-yl group; an oxadiazolyl group
such as a 1,3,4-oxadiazol-2-yl group; a tetrazolyl group such as a
5-tetrazolyl group; a pyridazinyl group such as a 3-pyridazinyl or
4-pyridazinyl group; a pyrimidinyl group such as a 2-pyrimidinyl,
4-pyrimidinyl or 5-pyrimidinyl group; a pyrazinyl group; an
oxazinyl group such as a 1,4-oxazin-2-yl or 1,4-oxazin-3-yl group;
and a thiazinyl group such as a 1,4-thiazin-2-yl or
1,4-thiazin-3-yl group; and the unsubstituted condensed hetero aryl
group includes, for example, an indolyl group such as an
indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl or
indol-7-yl group; an indazolyl group such as an indazol-2-yl,
indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl or
indazol-7-yl group; a benzofuranyl group such as a benzofuran-2-yl,
benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl
or benzofuran-7-yl group; a benzothiophenyl group such as a
benzothiophen-2-yl, benzothiophen-3-yl, benzothiophen-4-yl,
benzothiophen-5-yl, benzothiophen-6-yl or benzothiophen-7-yl group;
a benzimidazolyl group such as a benzimidazol-2-yl,
benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl or
benzimidazol-7-yl group; a benzoxazolyl group such as a
benzoxazol-2-yl, benzoxazol-4-yl, benzoxazol-5-yl, benzoxazol-6-yl
or benzoxazol-7-yl group; a benzothiazolyl group such as a
benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl,
benzothiazol-6-yl or benzothiazol-7-yl group; a quinolyl group such
as a 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl,
7-quinolyl or 8-quinolyl group: an isoquinolyl group such as a
1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl or 8-isoquinolyl group;
a benzoxazinyl group such as a 1,4-benzoxazin-2-yl or
1,4-benzoxazin-3-yl group; a benzothiazinyl group such as a
1,4-benzothiazin-2-yl or 1,4-benzothiazin-3-yl group; a
pyrrolo[2,3-b]pyridyl group such as a pyrrolo[2,3-b]pyrid-2-yl or
pyrrolo[2,3-b]pyrid-3-yl; a furo[2,3-b]pyridyl group such as a
furo[2,3-b]pyrid-2-yl or furo[2,3-b]pyrid-3-yl group; a
thieno[2,3-b]pyridyl group such as a thieno[2,3-b]pyrid-2-yl or
thieno[2,3-b]pyrid-3-yl group; a naphthylidinyl group such as a
1,8-naphthylidin-2-yl, 1,8-naphthylidin-3-yl, 1,5-naphthylidin-2-yl
and 1,5-naphthylidin-3-yl group; an imidazopyridyl group such as an
imidazo[4,5-b]pyrid-2-yl or imidazo[4,5-b]pyrid-5-yl group; an
oxazolopyridyl group such as an oxazolo[4,5-b]pyrid-2-yl or
oxazolo[5,4-b]pyrid-2-yl group; and a thiazolopyridyl group such as
a thiazolo[4,5-b]pyrid-2-yl or thiazolo[4,5-c]pyrid-2-yl group.
[0067] The monocyclic hetero aryl group is preferably a 5- or
6-membered ring group having from 1 to 3 hetero atoms selected from
the group consisting of a nitrogen atom, an oxygen atom and a
sulfur atom and includes the above-exemplified pyrrolyl group,
furyl group, thienyl group, pyridyl group, imidazolyl group,
pyrazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group,
triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridazinyl
group, pyrimidinyl group or pyrazinyl group. The condensed hetero
aryl group is preferably a condensed ring group of a benzene ring
with the 5- or 6-membered monocyclic hetero aryl group having from
1 to 3 hetero atoms selected from the group consisting of a
nitrogen atom, oxygen atom and sulfur atom and includes the
above-exemplified indolyl group, benzofuranyl group,
benzothiophenyl group, benzimidazolyl group, benzoxazolyl group,
benzothiazolyl group, quinolyl group or isoquinolyl group; more
preferably an imidazolyl group, oxazolyl group, pyridyl group,
indolyl group, quinolyl group or isoquinolyl group; still more
preferably a pyridyl group, indolyl group, quinolyl group or
isoquinolyl group; and most preferably a pyridyl group, quinolyl
group or isoquinolyl group; particularly most preferably a pyridyl
group.
[0068] In the case where the above group X represents an aryl group
having from 6 to 10 carbon atoms or a mono- or dicyclic, 5- to
10-membered hetero aryl group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom, the aryl group and the hetero aryl group may have
from 1 to 3 substituents .alpha. as described above.
[0069] In the case where the substituent .alpha. represents a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, a straight or branched chain alkoxy group having from 1 to 4
carbon atoms, a straight or branched chain alkylthio group having
from 1 to 4 carbon atoms, a halogen atom, or a straight or branched
chain dialkylamino group in which each alkyl group may be the same
or different and each has from 1 to 4 carbon atoms, these groups
may include the same groups as described above in the definition of
R.sup.3. However, in the case where the substituent .alpha.
represents a straight or branched chain alkyl group having from 1
to 6 carbon atoms, the alkyl group preferably includes a methyl,
ethyl, propyl, isopropyl, butyl or t-butyl, more preferably a
methyl, isopropyl or t-butyl group.
[0070] In the case where the substituent .alpha. represents an
aralkyloxycarbonylamino group in which the aralkyl moiety has from
7 to 12 carbon atoms, the group includes, for example, a
benzyloxycarbonylamino group.
[0071] In the case where the substituent .alpha. represents a
straight or branched chain halogenated alkyl group having from 1 to
4 carbon atoms, the halogenated alkyl group includes, for example,
a chloromethyl, bromomethyl, fluoromethyl, iodomethyl,
difluoromethyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,2-trichloroethyl or trichloromethyl
group; preferably a fluoromethyl having from 1 to 3 fluorine atoms;
more preferably a trifluoromethyl.
[0072] In the case where the substituent a represents a straight or
branched chain aliphatic acyloxy group having from 1 to 5 carbon
atoms, the acyloxy group includes, for example, a formyloxy,
acetoxy, propionyloxy, butyryloxy, acroyloxy, methacroyloxy or
crotonoyloxy group; preferably an alkanoyloxy group having from 1
to 4 carbon atoms; more preferably an alkanoyloxy group having one
or two carbon atoms; most preferably an acetoxy group.
[0073] In the case where the substituent a represents a straight or
branched chain halogenated alkoxy group having from 1 to 4 carbon
atoms, the halogenated alkoxy group includes, for example, a
chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy,
difluoromethoxy, trifluoromethoxy, pentafluoroethoxy, 2,2,2-
trifluoroethoxy, 2,2,2-trichloroethoxy, trichloromethoxy or
2,2,3,3-tetrafluoropropoxy group; preferably a straight or branched
chain halogenated alkoxy group having from 1 to 3 carbon atoms;
more preferably a methoxy group having from 1 to 3 fluorine atoms
or a 2,2,3,3-tetrafluoropropoxy group; most preferably a
trifluoromethoxy or 2,2,3,3-tetrafluoropropoxy group (particularly
a 2,2,3,3-tetrafluoropropoxy group).
[0074] In the case where the substituent .alpha. represents a
straight or branched chain aliphatic acyl group having from 1 to 5
carbon atoms, the acyl group includes, for example, a formyl,
acetyl, propionyl, butyryl, acroyl, methacroyl or crotonoyl group;
preferably a straight or branched chain aliphatic acyl group having
2 or 3 carbon atoms; more preferably an acetyl group.
[0075] In the case where the substituent .alpha. represents a
straight or branched chain alkylenedioxy group having from 1 to 4
carbon atoms, the alkylenedioxy group includes, for example, a
methylenedioxy, ethylenedioxy, trimethylenedioxy,
tetramethylenedioxy or propylenedioxy group; preferably a
methylenedioxy or ethylenedioxy group; more preferably a
methylenedioxy group.
[0076] In the case where the substituent .alpha. represents an
aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .beta. described later, the aralkyloxy
group includes, for example, a benzyloxy, phenethyloxy,
3-phenylpropoxy, 4-phenylbutoxy, 1-naphthylmethoxy or
2-naphthylmethoxy group; preferably an unsubstituted aralkyloxy
having from 7 to 12 carbon atoms (for example, a-benzyloxy,
2-phenethyloxy, 1-naphthylmethoxy or 2-naphthylmethoxy group); more
preferably a benzyloxy group.
[0077] In the case where the substituent .alpha. represents a
straight or branched chain alkylsulfonyl group having from 1 to 4
carbon atoms, the alkylsulfonyl group includes, for example, a
methanesulfonyl, ethanesulfonyl, propanesulfonyl,
isopropanesulfonyl, butanesulfonyl, isobutanesulfonyl,
s-butanesulfonyl or t-butanesulfonyl group, preferably a
methanesulfonyl, ethanesulfonyl or isopropanesulfonyl group;
particularly preferably an alkylsulfonyl group having from one or
two carbon atoms (particularly a methanesulfonyl group).
[0078] In the case where the substituent .alpha. represents a
straight or branched chain monoalkylamino group in which the alkyl
moiety has from 1 to 4 carbon atoms, the monoalkylamino group
includes, for example, a methylamino, ethylamino, propylamino,
isopropylamino, butylamino, isobutylamino, s-butylamino or
t-butylamino group; preferably a methylamino, ethylamino,
isopropylamino or t-butylamino group; more preferably a methylamino
group.
[0079] In the case where the substituent .alpha. represents a
straight or branched chain alkoxycarbonylamino group in which the
alkoxy moiety has from 1 to 4 carbon atoms, the alkoxycarbonylamino
group includes, for example, a methoxycarbonylamino,
ethoxycarbonylamino or t-butoxycarbonylamino group; preferably a
t-butoxycarbonylamino group.
[0080] In the case where the substituent .alpha. represents an
aralkyl group having from 7 to 12 carbon atoms in the aryl moiety
which may have from 1 to 3 substituents .beta. described later, the
aralkyl group includes, for example, a benzyl, phenethyl,
3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl,
1-naphthylmethoxy or 2-naphthylmethoxy group; preferably a benzyl
group which may have from 1 to 3 substituents .beta. described
later on the phenyl moiety; more preferably a benzyl group.
[0081] In the case where the substituent .alpha. represents an aryl
group having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta., which may be the same or different, described
later, the aryl group includes, for example, a phenyl, naphthyl,
methylphenyl, (trifluoromethyl)phenyl, hydroxyphenyl,
methoxyphenyl, ethoxyphenyl, (trifluoromethoxy)phenyl,
methylenedioxyphenyl, (hydroxymethyl)phenyl, fluorophenyl,
chlorophenyl, bromophenyl, nitrophenyl, formylphenyl, cyanophenyl,
carboxyphenyl, aminophenyl, (dimethylamino)phenyl,
(aminomethyl)phenyl, (2-aminoethyl)phenyl,
[(N,N-dimethylamino)methyl]phe- nyl, (t-butoxycarbonylamino)phenyl,
(benzyloxycarbonylamino)phenyl or 4-hydroxy-3,5-dimethylphenyl
group; preferably a phenyl group which may have from 1 to 3
substituents .beta. described later (particularly, a phenyl,
methylphenyl, (trifluoromethyl)phenyl, hydroxyphenyl,
methoxyphenyl, (trifluoromethoxy)phenyl, methylenedioxyphenyl,
(hydroxymethyl)phenyl, fluorophenyl, chlorophenyl, nitrophenyl,
formylphenyl, cyanophenyl, carboxyphenyl, dimethylaminophenyl,
aminomethylphenyl, (N,N-dimethylaminomethyl)phenyl or
4-hydroxy-3,5-dimethylphenyl group); more preferably a phenyl,
methylphenyl, (trifluoromethyl)phenyl, hydroxyphenyl,
methoxyphenyl, (trifluoromethoxy)phenyl, methylenedioxyphenyl,
(hydroxymethyl)phenyl, fluorophenyl, chlorophenyl, nitrophenyl,
formylphenyl, cyanophenyl, carboxyphenyl, (dimethylamino)phenyl,
(aminomethyl)phenyl, (N,N-dimethylaminomethyl)phenyl or
4-hydroxy-3,5-dimethoxyphenyl group; most preferably a phenyl,
(trifluoromethyl)phenyl, methoxyphenyl, (hydroxymethyl)phenyl,
(trifluoromethoxy)phenyl, fluorophenyl, fluorophenyl, chlorophenyl,
chlorophenyl, nitrophenyl, formylphenyl, carboxyphenyl,
dimethylaminophenyl, (N,N-dimethylaminomethyl)phenyl or
4-hydroxy-3,5-dimethylphenyl group; particularly most preferably a
phenyl, (trifluoromethoxy)phenyl, methoxyphenyl, fluorophenyl,
chlorophenyl, formylphenyl, carboxyphenyl or (dimethylamino)phenyl
group.
[0082] In the case where the substituent .alpha. represents an
aryloxy group having from 6 to 10 carbon atoms in the aryl moiety
which may have from 1 to 3 substituents .beta. described later, the
aryloxy group includes, for example, a phenoxy, naphthoxy,
methylphenoxy, (trifluoromethyl)phenoxy, methoxyphenoxy,
ethoxyphenoxy, fluorophenoxy, chlorophenoxy, bromophenoxy or
methylenedioxyphenoxy group; preferably a phenoxy group which may
have from 1 to 3 substituents .beta. described later (particularly
a phenoxy group).
[0083] In the case where the substituent .alpha. represents an
arylthio group having from 6 to 10 carbon atoms in the aryl moiety
which may have from 1 to 3 substituents .beta. described later, the
arylthio group includes, for example, a phenylthio,
methylphenylthio, (trifluoromethyl)phenylthio, methoxyphenylthio,
ethoxyphenylthio, chlorophenylthio, bromophenylthio,
methylenedioxyphenylthio or naphthylthio group; preferably a
phenylthio group which may have from 1 to 3 substituents .beta.
described later (particularly a phenylthio group).
[0084] In the case where the substituent .alpha. represents an
arylsulfonyl group having from 6 to 10 carbon atoms in the aryl
moiety which may have from 1 to 3 substituents .beta. described
later, the arylsulfonyl group includes, for example, a
phenylsulfonyl, methylphenylsulfonyl,
(trifluoromethyl)phenylsulfonyl, methoxyphenylsulfonyl,
ethoxyphenylsulfonyl, chlorophenylsulfonyl, bromophenylsulfonyl,
methylenedioxyphenylsulfonyl or naphthylsulfonyl group; preferably
a phenylsulfonyl group which may have from 1 to 3 substituents
.beta. described later.
[0085] In the case where the substituent .alpha. represents an
arylsulfonylamino group having from 6 to 10 carbon atoms in the
aryl moiety which may have from 1 to 3 substituents .beta.
described later (the nitrogen atom of the amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), the alkyl moiety of the substituent on
the nitrogen atom has the same meaning as defined above. The
arylsulfonylamino group includes, for example, a
(phenylsulfonyl)amino, (methylphenylsulfonyl)amino,
(trifluoromethylphenylsulfonyl)amino, (methoxyphenylsulfonyl)amino,
(ethoxyphenylsulfonyl)amino, chlorophenylsulfonylamino,
bromophenylsulfonylamino, methylenedioxyphenylsulfonylamino,
N-methyl-phenylsulfonylamino, (naphthylsulfonyl)amino or
N-methyl-naphthylsulfonylamino group; preferably a
(phenylsulfonyl)amino group which may have from 1 to 3 substituents
.beta. described later on the phenyl moiety or a
N-methyl-phenylsulfonylamino group (particularly a
phenylsulfonylamino or N-methyl-phenylsulfonylamino group).
[0086] In the case where the substituent .alpha. represents a mono-
or dicyclic, 5- to 10-membered hetero aryl group containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta. described later, the unsubstituted hetero aryl
group includes, for example, a furyl, thienyl, oxazolyl,
isoxazolyl, thiazolyl, imidazolyl, quinolyl, isoquinolyl, indolyl
or pyridyl group; preferably an imidazolyl, quinolyl or pyridyl
group; particularly preferably a pyridyl group. The group having a
substituent includes methylpyridyl, (trifluoromethyl)pyridyl,
hydroxypyridyl, methoxypyridyl, ethoxypyridyl,
(trifluoromethoxy)pyridyl, (hydroxymethyl)pyridyl, fluoropyridyl,
chloropyridyl, bromopyridyl, nitropyridyl, formylpyridyl,
cyanopyridyl, carboxypyridyl, aminopyridyl, (dimethylamino)pyridyl,
(aminomethyl)pyridyl, (2-aminoethyl)pyridyl,
(N,N-dimethylaminomethyl)pyr- idyl, (t-butoxycarbonylamino)pyridyl
or (benzyloxycarbonylamino)pyridyl group; preferably a pyridyl
group which may have from 1 to 3 substituents .beta. described
later (for example, a methylpyridyl, (trifluoromethyl)pyridyl,
hydroxypyridyl, methoxypyridyl, (trifluoromethoxy)pyridyl,
fluoropyridyl, chloropyridyl, nitropyridyl, formylpyridyl,
cyanopyridyl, carboxypyridyl, aminopyridyl, dimethylaminopyridyl or
(N,N-dimethylaminomethyl)pyridyl) group or an imidazolyl group (the
nitrogen atom of the ring may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms,
particularly a N-methylimidazolyl group); more preferably a
(trifluoromethyl)pyridyl, methoxypyridyl, fluoropyridyl,
chloropyridyl, nitropyridyl, cyanopyridyl, aminopyridyl or
dimethylaminopyridyl group.
[0087] In the case where the substituent .alpha. represents a mono-
or dicyclic, 5- to 10-membered hetero aryloxy group containing from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta. described later, the hetero aryloxy group
includes, for example, a furyloxy, thienyloxy, oxazolyloxy,
isoxazolyloxy, thiazolyloxy, imidazolyloxy, quinolyloxy,
isoquinolyloxy, indolyloxy or pyridyloxy group, preferably a
pyridyloxy group which may have from 1 to 3 substituents .beta.
described later; particularly preferably a pyridyloxy group.
[0088] In the case where the substituent (.alpha.represents a mono-
or dicyclic, 5- to 10-membered hetero arylthio group containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .beta. described later, the hetero arylthio group
includes, for example, a furylthio, thienylthio, oxazolylthio,
isoxazolylthio, thiazolylthio, imidazolylthio, quinolylthio,
isoquinolylthio, indolylthio or pyridylthio group; preferably a
pyridylthio group which may have from 1 to 3 substituents .beta.
described later; particularly preferably a pyridylthiogroup.
[0089] In the case where the substituent .alpha. represents a mono-
or dicyclic, 5- to 10-membered hetero arylsulfonyl group containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .beta. described later, the hetero arylsulfonyl
group includes, for example, a furylsulfonyl, thienylsulfonyl,
oxazolylsulfonyl, isoxazolylsulfonyl, thiazolylsulfonyl,
imidazolylsulfonyl, quinolylsulfonyl, isoquinolylsulfonyl,
indolylsulfonyl or pyridinesulfonyl group; preferably a
pyridylsulfonyl group which may have from 1 to 3 substituents
.beta. described later; particularly preferably a pyridylsulfonyl
group.
[0090] In the case where the substituent .alpha. represents a mono-
or dicyclic, 5- to 10-membered hetero arylsulfonylamino group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta. described later in the
hetero aryl moiety (the nitrogen atom of the amino moiety may be
substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms), the hetero arylsulfonylamino group
includes, for example, a furylsulfonylamino, thienylsulfonylamino,
oxazolylsulfonylamino, isoxazolylsulfonylamino,
thiazolylsulfonylamino, imidazolylsulfonylamino,
N-methyl-imidazolylsulfo- nylamino, quinolylsulfonylamino,
isoquinolylsulfonylamino, indolylsulfonylamino,
pyridylsulfonylamino or N-methylpyridylsulfonylamin- o group;
preferably a pyridylsulfonylamino group which may have from 1 to 3
substituents .beta. described later on the pyridyl moiety (the
nitrogen atom of the amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms); particularly preferably a pyridinesulfonylamino or
N-methyl-pyridinesulfonylamino group.
[0091] In the case where the substituent .alpha. represents a mono-
or dicyclic, 5- to 10-membered saturated heterocyclic group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom, the
saturated heterocyclic group includes, for example, a morpholinyl,
thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl,
imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl or piperazinyl
group; preferably a morpholinyl, thiomorpholinyl, pyrrolidinyl,
piperidyl or piperazinyl group (particularly a piperidyl
group).
[0092] In the case where the substituent .beta. represents a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, a straight or branched chain alkoxy group having from 1 to 4
carbon atoms, a halogen atom, or a straight or branched chain
dialkylamino group in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, these groups may
include the same groups as described above in the definition of
R.sup.3.
[0093] In the case where the substituent .beta. represents a
straight or branched chain halogenated alkyl group having from 1 to
4 carbon atoms, a straight or branched chain halogenated alkoxy
group having from 1 to 4 carbon atoms, a straight or branched chain
alkylenedioxy group having from 1 to 4 carbon atoms, a straight or
branched chain aliphatic acyl group having from 1 to 5 carbon
atoms, a straight or branched chain monoalkylamino group in which
the alkyl moiety has from 1 to 4 carbon atoms, a straight or
branched chain alkoxycarbonylamino group in which the alkoxy moiety
has from 1 to 4 carbon atoms, or an aralkyloxycarbonylamino group
in which the aralkyl moiety has from 7 to 12 carbon atoms, these
groups may include the same groups as described above in the
definition of .alpha..
[0094] In the case where the substituent .beta. represents a
straight or branched chain hydroxyalkyl group having from 1 to 4
carbon atoms, the hydroxyalkyl group includes, for example, a
hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl or 4-hydroxybutyl
group, preferably a hydroxymethyl group.
[0095] In the case where the substituent .beta. represents a
straight or branched chain aminoalkyl group having from 1 to 4
carbon atoms, the aminoalkyl group includes, for example, an
aminomethyl, 2-aminoethyl, 3-aminopropyl or 4-aminobutyl group;
preferably an aminomethyl or aminoethyl group; more preferably an
aminomethyl group.
[0096] In the case where the substituent .beta. represents a
monoalkylaminoalkyl group in which the monoalkylamino moiety has
one straight or branched chain alkyl group having from 1 to 4
carbon atoms and the alkyl moiety is a straight or branched chain
alkyl having from 1 to 4 carbon atoms, the monoalkylaminoalkyl
group includes, for example, a N-methylaminomethyl,
N-ethylaminomethyl, N-methylaminoethyl, N-ethylaminoethyl,
N-methylaminopropyl or N-methylaminobutyl group; preferably a
N-methylaminomethyl or N-methylaminoethyl group.
[0097] In the case where the substituent .beta. represents a
dialkylaminoalkyl group in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different, and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, the dialkylaminoalkyl group includes, for example, a
N,N-dimethylaminomethyl, N,N-diethylaminomethyl,
N,N-dimethylaminoethyl, N,N-diethylaminoethyl,
N,N-dimethylaminopropyl or N,N-dimethylaminobutyl group; preferably
a N,N-dimethylaminomethyl or N,N-dimethylaminoethyl group; more
preferably a N,N-dimethylaminomethyl group.
[0098] Therefore, in the case where X represents a substituted or
unsubstituted aryl group having from 6 to 10 carbon atoms or a
substituted or unsubstituted mono- or dicyclic, 5- to 10-membered
hetero aryl group containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, nitrogen atom and sulfur
atom, specific example of these groups preferably includes a
phenyl, 1-naphthyl, 2-naphthyl, m-tolyl, p-tolyl, 3-ethylphenyl,
4-ethylphenyl, 3-isopropylphenyl, 4-isopropylphenyl,
3-t-butylphenyl, 4-t-butylphenyl, 4-chloromethylphenyl,
4-bromomethylphenyl, 4-fluoromethylphenyl, 4-iodomethylphenyl,
3-difluoromethylphenyl, 4-trifluoromethylphenyl,
4-pentafluoroethylphenyl, 4-trichloromethylphenyl, 3-hydroxyphenyl,
4-hydroxyphenyl, 3-acetoxyphenyl, 4-acetoxyphenyl,
5-acetoxy-2-hydroxy-3,4,6-trimethylphenyl, 3-methoxyphenyl,
4-methoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl,
3-isopropoxyphenyl, 4-isopropoxyphenyl, 3,4-methylenedioxyphenyl,
benzyloxyphenyl, phenethyloxyphenyl, 1-naphthylmethoxyphenyl,
3-methylthiophenyl, 4-methylthiophenyl, 3-ethylthiophenyl,
4-ethylthiophenyl, 3-isopropylthiophenyl, 4-isopropylthiophenyl,
3-methanesulfonylphenyl, 4-methanesulfonylphenyl,
3-ethanesulfonylphenyl, 4-ethanesulfonylphenyl,
3-isopropanesulfonylphenyl, 4-isopropanesulfonylphenyl,
3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl,
3-bromophenyl, 4-bromophenyl, 4-nitrophenyl, 4-aminophenyl,
3-methylaminophenyl, 4-ethylaminophenyl, 3-propylaminophenyl,
4-butylaminophenyl, 3-dimethylaminophenyl, 4-diethylaminophenyl,
3-dipropylaminophenyl, 4-dibutylaminophenyl, 3-benzylphenyl,
4-benzylphenyl, 3-phenethylphenyl, 4-(1-naphthylmethyl)phenyl,
3-biphenylyl, 4-biphenylyl, 3-(4-methylphenyl)phenyl,
4-(4-methylphenyl)phenyl, 3-(4-ethylphenyl)phenyl,
3-(4-trifluoromethylphenyl)phenyl,
4-(4-trifluoromethylphenyl)phenyl, 4-(2-hydroxyphenyl)phenyl,
4-(3-hydroxyphenyl)phenyl, 4-(4-hydroxyphenyl)phenyl,
4-(4-hydroxy-3,5-dimethylphenyl)phenyl, 3-(4-methoxyphenyl)phenyl,
4-(2-methoxyphenyl)phenyl, 4-(3-methoxyphenyl)phenyl,
4-(4-methoxyphenyl)phenyl, 3-(2,4-dimethoxyphenyl)phenyl,
4-(2,4-dimethoxyphenyl)phenyl, 3-(2,5-dimethoxyphenyl)phenyl,
4-(2,5-dimethoxyphenyl)phenyl, 4-(3-hydroxymethylphenyl)phenyl,
4-(4-hydroxymethylphenyl)phenyl, 4-(3-fluorophenyl)phenyl,
4-(4-fluorophenyl)phenyl, 4-(3-chlorophenyl)phenyl,
4-(4-chlorophenyl)phenyl, 4-(3-bromophenyl)phenyl,
4-(4-bromophenyl)phenyl, 3-(3,4-methylenedioxyphenyl)phenyl,
4-(3,4-methylenedioxyphenyl)phenyl, 4-(2-formylphenyl)phenyl,
4-(3-formylphenyl)phenyl, 4-(4-formylphenyl)phenyl,
4-(3-carboxyphenyl)phenyl, 4-(4-carboxyphenyl)phenyl,
4-(3-N,N-dimethylaminomethylphenyl)phenyl,
4-(4-N,N-dimethylaminomethylph- enyl)phenyl, 3-benzylphenyl,
4-benzylphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl,
3-phenylthiophenyl, 4-phenylthiophenyl, 3-phenylsulfonylphenyl,
4-phenylsulfonylphenyl, 3-(phenylsulfonylamino)ph- enyl,
4-(phenylsulfonylamino)phenyl,
3-(N-methylphenylsulfonylamino)phenyl- ,
4-(N-methylphenylsulfonylamino)phenyl, 3-(imidazol-1-yl)phenyl,
4-(imidazol-1-yl)phenyl, 3-(1-methylimidazol-4-yl)phenyl,
4-(1-methylimidazol-4-yl)phenyl, 3-(2-furyl)phenyl,
4-(2-furyl)phenyl, 3-(2-thienyl)phenyl, 4-(2-thienyl)phenyl,
3-(3-thienyl)phenyl, 4-(3-thienyl)phenyl, 3-(2-pyridyl)phenyl,
4-(2-pyridyl)phenyl, 4-(2-trifluoromethylpyridin-5-yl)phenyl,
4-(2-methoxypyridin-5-yl)phenyl, 4-(2-nitropyridin-5-yl)phenyl,
4-(2-N,N-dimethylaminopyridin-5-yl)phenyl, 3-(3-pyridyl)phenyl,
4-(3-pyridyl)phenyl, 3-(4-pyridyl)phenyl, 4-(4-pyridyl)phenyl,
4-(imidazol-1-ylthio)phenyl, 4-(2-furylthio)phenyl,
4-(2-thienylthio)phenyl, 4-(2-pyridylthio)phenyl,
4-(4-pyridylthio)phenyl- , 3-(2-pyridylsulfonyl)phenyl,
4-(2-pyridylsulfonyl)phenyl, 3-(3-pyridylsulfonyl)phenyl,
4-(3-pyridylsulfonyl)phenyl, 3-(2-pyridylsulfonylamino)phenyl,
3-(N-methyl-2-pyridylsulfonylamino)phen- yl,
4-(2-pyridylsulfonylamino)phenyl,
4-(N-methyl-2-pyridylsulfonylamino)p- henyl,
3-(3-pyridylsulfonylamino)phenyl,
3-(N-methyl-3-pyridylsulfonylamin- o)phenyl,
4-(3-pyridylsulfonylamino)phenyl, 4-(N-methyl-3-pyridylsulfonyla-
mino)phenyl, 3-(oxazol-2-yl)phenyl, 4-(oxazol-2-yl)phenyl,
3-(oxazol-4-yl)phenyl, 4-(oxazol-4-yl)phenyl,
3-(oxazol-5-yl)phenyl, 4-(oxazol-5-yl)phenyl,
3-(thiazol-2-yl)phenyl, 4-(thiazol-2-yl)phenyl,
3-(thiazol-4-yl)phenyl, 4-(thiazol-4-yl)phenyl,
3-(thiazol-5-yl)phenyl, 4-(thiazol-5-yl)phenyl,
4-(piperidin-1-yl)phenyl, 1-methyl-2-pyrrolyl, 1-phenyl-2-pyrrolyl,
1-benzyl-2-pyrrolyl, 5-methyl-2-furyl, 5-phenyl-2-furyl,
5-methyl-2-thienyl, 5-phenyl-2-thienyl, 5-methyl-3-thienyl,
5-phenyl-3-thienyl, 1-methyl-3-pyrazolyl, 1-phenyl-3-pyrazolyl,
3-imidazolyl, 1-methyl-2-imidazolyl, 1-phenyl-2-imidazolyl,
1-methyl-4-imidazolyl, 1-phenyl-4-imidazolyl,
1-methyl-2-phenyl-4-imidazolyl, 1,5-dimethyl-2-phenyl-4-imidazolyl,
1,4-dimethyl-2-phenyl-5-imidazolyl, 4-oxazolyl, 5-oxazolyl,
2-methyl-4-oxazolyl, 2-phenyl-4-oxazolyl, 2-methyl-5-oxazolyl,
2-phenyl-5-oxazolyl, 4-methyl-2-phenyl-5-oxazolyl,
5-methyl-2-phenyl-4-oxazolyl, 4-thiazolyl, 5-thiazolyl,
2-methyl-4-thiazolyl, 2-phenyl-4-thiazolyl, 2-methyl-5-thiazolyl,
2-phenyl-5-thiazolyl, 4-methyl-2-phenyl-5-thiazolyl,
5-methyl-2-phenyl-4-thiazolyl, 1-methyl-3-pyrazolyl,
1-phenyl-3-pyrazolyl, 3-methyl-5-isoxazolyl 3-phenyl-5-isoxazolyl,
2-pyridyl, 3-pyridyl, 4-pyridyl, 3-methyl-5-pyridyl,
3-ethyl-5-pyridyl, 3-phenyl-5-pyridyl, 2-methyl-5-pyridyl,
2-ethyl-5-pyridyl, 2-phenyl-5-pyridyl,
2-(4-methoxyphenyl)-5-pyridyl, 2-(4-fluorophenyl)-5-pyridyl,
2-hydroxy-5-pyridyl, 2-methoxy-5-pyridyl, 2-ethoxy-5-pyridyl,
2-isopropoxy-5-pyridyl, 2-(2,2,3,3-tetrafluoropropoxy-
phenyl)-5-pyridyl, 2-benzyloxy-5-pyridyl, 2-methylthio-5-pyridyl,
2-ethylthio-5-pyridyl, 2-isopropylthio-5-pyridyl,
2-methanesulfonyl-5-pyr- idyl, 2-ethanesulfonyl-5-pyridyl,
2-isopropanesulfonyl-5-pyridyl, 2-benzyl-5-pyridyl,
2-phenoxy-5-pyridyl, 2-phenylthio-5-pyridyl,
2-phenylsulfonyl-5-pyridyl, 2-phenylsulfonylamino-5-pyridyl,
2-(N-methyl-phenylsulfonylamino)-5-pyridyl, 3-methyl-6-pyridyl,
3-phenyl-6-pyridyl, 2-methyl-6-pyridyl, 2-phenyl-6-pyridyl,
2-methyl-4-pyrimidinyl, 2-phenyl-4-pyrimidinyl,
2-methoxy-4-pyrimidinyl, 2-ethoxy-4-pyrimidinyl,
2-isopropoxy-4-pyrimidinyl, 2-methylthio-4-pyrimidinyl
2-ethylthio-4-pyrimidinyl, 2-isopropylthio-4-pyrimidinyl,
2-phenylthio-4-pyrimidinyl, 2-methanesulfonyl-4-pyrimidinyl,
2-ethanesulfonyl-4-pyrimidinyl, 2-isopropylsulfonyl-4-pyrimidinyl,
2-phenylsulfonyl-4-pyrimidinyl, 2-methyl-5-pyrimidinyl,
2-phenyl-5-pyrimidinyl, 2-methoxy-5-pyrimidinyl,
2-ethoxy-5-pyrimidinyl, 2-isopropoxy-5-pyrimidinyl,
2-methylthio-5-pyrimidinyl, 2-ethylthio-5-pyrimidinyl,
2-isopropylthio-5-pyrimidinyl, 2-phenylthio-5-pyrimidinyl,
2-methanesulfonyl-5-pyrimidinyl, 2-ethanesulfonyl-5-pyrimidinyl,
2-isopropylsulfonyl-5-pyrimidinyl, 2-phenylsulfonyl-5-pyrimidinyl,
2-indolyl, 3-indolyl, 1-methyl-2-indolyl, 1-methyl-3-indolyl,
2-benzimidazolyl, 1-methyl-2-benzimidazolyl, 2-benzoxazolyl,
2-benzothiazolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl,
1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl or 8-isoquinolyl
group;
[0099] preferably a phenyl, 1-naphthyl, 2-naphthyl, m-tolyl,
p-tolyl, 3-ethylphenyl, 4-ethylphenyl, 3-isopropylphenyl,
4-isopropylphenyl, 4-trifluoromethylphenyl, 3-hydroxyphenyl,
4-hydroxyphenyl, 4-hydroxy-3,5-dimethylphenyl, 3-acetoxyphenyl,
4-acetoxyphenyl, 5-acetoxy-2-hydroxy-3,4,6-trimethylphenyl,
3-methoxyphenyl, 4-methoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl,
3-isopropoxyphenyl, 4-isopropoxyphenyl, 3,4-methylenedioxyphenyl,
benzyloxyphenyl, 3-methylthiophenyl, 4-methylthiophenyl,
3-ethylthiophenyl, 4-ethylthiophenyl, 3-methanesulfonylphenyl,
4-methanesulfonylphenyl, 3-ethanesulfonylphenyl,
4-ethanesulfonylphenyl, 3-fluorophenyl, 4-fluorophenyl,
3-chlorophenyl, 4-chlorophenyl, 4-diethylaminophenyl,
3-benzylphenyl, 4-benzylphenyl, 3-biphenylyl, 4-biphenylyl,
3-(4-methylphenyl)phenyl, 4-(4-methylphenyl)phenyl,
3-(4-ethylphenyl)phenyl, 3-(4-trifluoromethylphenyl)phenyl,
4-(4-trifluoromethylphenyl)phenyl, 4-(2-hydroxyphenyl)phenyl,
4-(3-hydroxyphenyl)phenyl, 4-(4-hydroxyphenyl)phenyl,
4-(4-hydroxy-3,5-dimethylphenyl)phenyl, 3-(4-methoxyphenyl)phenyl,
4-(2-methoxyphenyl)phenyl, 4-(3-methoxyphenyl)phenyl,
4-(4-methoxyphenyl)phenyl, 3-(2,4-dimethoxyphenyl)phenyl,
4-(2,4-dimethoxyphenyl)phenyl, 3-(2,5-dimethoxyphenyl)phenyl,
4-(2,5-dimethoxyphenyl)phenyl, 4-(3-hydroxymethylphenyl)phenyl,
4-(4-hydroxymethylphenyl)phenyl, 4-(3-fluorophenyl)phenyl,
4-(4-fluorophenyl)phenyl, 4-(3-chlorophenyl)phenyl,
4-(4-chlorophenyl)phenyl, 3-(3,4-methylenedioxyphenyl)phenyl,
4-(3,4-methylenedioxyphenyl)phenyl, 2-formylphenyl, 3-formylphenyl,
4-formylphenyl, 3-carboxyphenyl, 4-carboxyl,
3-N,N-dimethylaminomethylphe- nyl, 4-N,N-dimethylaminomethylphenyl,
3-phenoxyphenyl, 4-phenoxyphenyl, 3-phenylthiophenyl,
4-phenylthiophenyl, 3-phenylsulfonylphenyl, 4-phenylsulfonylphenyl,
3-(phenylsulfonylamino)phenyl, 4-(phenylsulfonylamino)phenyl,
3-(N-methylphenylsulfonylamino)phenyl,
4-(N-methylphenylsulfonylamino)phenyl, 3-(2-pyridyl)phenyl,
4-(2-pyridyl)phenyl, 4-(2-trifluoromethylpyridin-5-yl)phenyl,
4-(2-methoxypyridin-5-yl)phenyl, 4-(2-nitropyridin-5-yl)phenyl,
4-(2-N,N-dimethylaminopyridin-5-yl)phenyl, 3-(3-pyridyl)phenyl,
4-(3-pyridyl)phenyl, 3-(4-pyridyl)phenyl, 4-(4-pyridyl)phenyl,
4-(2-pyridyloxy)phenyl, 4-(4-pyridyloxy)phenyl,
4-(2-pyridylthio)phenyl, 4-(4-pyridylthio)phenyl,
3-(2-pyridylsulfonyl)phenyl, 4-(2-pyridylsulfonyl)phenyl,
3-(3-pyridylsulfonyl)phenyl, 4-(3-pyridylsulfonyl)phenyl,
3-(2-pyridylsulfonylamino)phenyl,
3-(N-methyl-2-pyridylsulfonylamino)phenyl,
4-(2-pyridylsulfonylamino)phen- yl,
4-(N-methyl-2-pyridylsulfonylamino)phenyl,
3-(3-pyridylsulfonylamino)p- henyl,
3-(N-methyl-3-pyridylsulfonylamino)phenyl,
4-(3-pyridylsulfonylamin- o)phenyl,
4-(N-methyl-3-pyridylsulfonylamino)phenyl, 4-(1-piperidinyl)phenyl,
3-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-methyl-5-pyridyl,
3-ethyl-5-pyridyl, 3-phenyl-5-pyridyl, 2-methyl-5-pyridyl,
2-ethyl-5-pyridyl, 2-phenyl-5-pyridyl, 2-hydroxy-5-pyridyl,
2-methoxy-5-pyridyl, 2-ethoxy-5-pyridyl, 2-isopropoxy-5-pyridyl,
2-(2,2,3,3-tetrafluoropropoxy)-5-pyridyl, 2-benzyloxy-5-pyridyl,
2-methylthio-5-pyridyl, 2-ethylthio-5-pyridyl,
2-isopropylthio-5-pyridyl, 2-methanesulfonyl-5-pyridyl,
2-ethanesulfonyl-5-pyridyl, 2-isopropanesulfonyl-5-pyridyl,
2-benzyl-5-pyridyl, 2-phenoxy-5-pyridyl, 2-phenylthio-5-pyridyl,
2-phenylsulfonyl-5-pyridyl, 2-phenylsulfonylamino-5-pyridyl,
2-(N-methyl-phenylsulfonylamino)-5-pyridyl,
2-(4-methoxyphenyl)-5-pyridyl- , 2-(4-fluorophenyl)-5-pyridyl,
3-methyl-6-pyridyl, 3-phenyl-6-pyridyl, 2-methyl-6-pyridyl,
2-phenyl-6-pyridyl, 2-quinolyl, 3-quinolyl, 4-quinolyl,
1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl or 8-isoquinolyl
group;
[0100] more preferably a phenyl, m-tolyl, p-tolyl, 3-hydroxyphenyl,
4-hydroxyphenyl, 4-hydroxy-3,5-dimethylphenyl, 3-acetoxyphenyl,
4-acetoxyphenyl, 5-acetoxy-2-hydroxy-3,4,6-trimethylphenyl,
3-chlorophenyl, 4-chlorophenyl, 3-benzylphenyl, 4-benzylphenyl,
3-biphenylyl, 4-biphenylyl, 4-(4-trifluoromethylphenyl)phenyl,
4-(2-hydroxyphenyl)phenyl, 4-(3-hydroxyphenyl)phenyl,
4-(4-hydroxyphenyl)phenyl, 4-(2-methoxyphenyl)phenyl,
4-(3-methoxyphenyl)phenyl, 4-(4-methoxyphenyl)phenyl,
4-(4-hydroxy-3,5-dimethylphenyl)phenyl, 4-(4-fluorophenyl)phenyl,
4-(4-chlorophenyl)phenyl, 4-(2-formylphenyl)phenyl,
4-(3-formylphenyl)phenyl, 4-(4-formylphenyl)phenyl,
4-(3-carboxyphenyl)phenyl, 4-(4-carboxyphenyl)phenyl,
4-(3-hydroxymethylphenyl)phenyl, 4-(4-hydroxymethylphenyl)phenyl,
4-(3-N,N-dimethylaminomethylphenyl)phenyl,
4-(4-N,N-dimethylaminomethylph- enyl)phenyl, 3-phenoxyphenyl,
4-phenoxyphenyl, 3-phenylthiophenyl, 4-phenylthiophenyl,
3-phenylsulfonylphenyl, 4-phenylsulfonylphenyl,
3-(phenylsulfonylamino)phenyl, 4-(phenylsulfonylamino)phenyl,
3-(N-methylphenylsulfonylamino)phenyl,
4-(N-methylphenylsulfonylamino)phe- nyl, 3-(2-pyridyl)phenyl,
4-(2-pyridyl)phenyl, 4-(3-trifluoromethylpyridin- -6-yl)phenyl,
4-(3-methoxypyridin-6-yl)phenyl, 4-(3-nitropyridin-6-yl)phen- yl,
4-(3-N,N-dimethylaminopyridin-6-yl)phenyl, 3-(3-pyridyl)phenyl,
4-(3-pyridyl)phenyl, 3-(4-pyridyl)phenyl, 4-(4-pyridyl)phenyl,
4-(2-pyridyloxy)phenyl, 4-(4-pyridyloxy)phenyl,
4-(2-pyridylthio)phenyl, 4-(4-pyridylthio)phenyl,
3-(2-pyridylsulfonyl)phenyl, 4-(2-pyridylsulfonyl)phenyl,
3-(3-pyridylsulfonyl)phenyl, 4-(3-pyridylsulfonyl)phenyl,
3-(2-pyridylsulfonylamino)phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-methoxy-5-pyridyl, 2-ethoxy-5-pyridyl, 2-isopropoxy-5-pyridyl,
2-(2,2,3,3-tetrafluoropropoxy)-5-pyridyl, 2-benzyloxy-5-pyridyl,
2-methylthio-5-pyridyl, 2-ethylthio-5-pyridyl,
2-methanesulfonyl-5-pyridyl, 2-ethanesulfonyl-5-pyridyl,
2-benzyl-5-pyridyl, 2-phenyl-5-pyridyl,
2-(4-methoxyphenyl)-5-pyridyl, 2-(4-fluorophenyl)-5-pyridyl,
3-phenyl-5-pyridyl, 2-phenyl-6-pyridyl, 3-phenyl-6-pyridyl,
2-phenoxy-5-pyridyl, 2-phenylthio-5-pyridyl,
2-phenylsulfonyl-5-pyridyl, 2-phenylsulfonylamino-5-pyridyl,
2-(N-methylphenylsulfonylamino)-5-pyridyl, 2-methyl-5-pyridyl,
3-quinolyl, 3-methyl-5-pyridyl, 3-quinolyl or 3-indolyl group;
[0101] most preferably a phenyl, p-tolyl, 4-fluorophenyl,
4-benzylphenyl, 4-biphenylyl, 4-(4-trifluoromethylphenyl)phenyl,
4-(2-hydroxyphenyl)pheny- l, 4-(3-hydroxyphenyl)phenyl,
4-(4-hydroxyphenyl)phenyl, 4-(2-methoxyphenyl)phenyl,
4-(3-methoxyphenyl)phenyl, 4-(4-methoxyphenyl)phenyl,
4-(4-hydroxy-3,5-dimethylphenyl)phenyl, 4-(4-fluorophenyl)phenyl,
4-(4-chlorophenyl)phenyl, 4-(2-formylphenyl)phenyl,
4-(3-formylphenyl)phenyl, 4-(4-formylphenyl)phenyl,
4-(3-carboxyphenyl)phenyl, 4-(4-carboxyphenyl)phenyl,
4-(3-hydroxymethylphenyl)phenyl, 4-(4-hydroxymethylphenyl)phenyl,
4-(3-N,N-dimethylaminomethylphenyl)pheny- l,
4-(4-N,N-dimethylaminomethylphenyl)phenyl, 4-phenoxyphenyl,
4-phenylthiophenyl, 4-phenylsulfonylphenyl,
4-(phenylsulfonylamino)phenyl- , 4-(2-pyridyl)phenyl,
4-(3-trifluoromethylpyridin-6-yl)phenyl,
4-(3-methoxypyridin-6-yl)phenyl, 4-(3-nitropyridin-6-yl)phenyl,
4-(3-N,N-dimethylaminopyridin-6-yl)phenyl, 4-(3-pyridyl)phenyl,
4-(4-pyridyl)phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-methoxy-5-pyridyl, 2-ethoxy-5-pyridyl, 2-isopropoxy-5-pyridyl,
2-(2,2,3,3-tetrafluoropropoxy)-5-pyridyl, 2-benzyloxy-5-pyridyl,
2-methylthio-5-pyridyl, 2-ethylthio-5-pyridyl,
2-methanesulfonyl-5-pyridy- l, 2-ethanesulfonyl-5-pyridyl,
2-benzyl-5-pyridyl, 2-phenyl-5-pyridyl, 3-phenyl-5-pyridyl,
3-phenyl-6-pyridyl, 2-(4-methoxyphenyl)-5-pyridyl,
2-(4-fluorophenyl)-5-pyridyl, 2-phenyl-6-pyridyl,
2-phenoxy-5-pyridyl, 2-phenylthio-5-pyridyl,
2-phenylsulfonyl-5-pyridyl, 2-phenylsulfonylamino-5-pyridyl,
2-(N-methylphenylsulfonylamino)-5-pyridy- l, 2-methyl-5-pyridyl or
3-methyl-5-pyridyl group.
[0102] In the case where Y represents a group of the formula:
>N--R.sup.5 (wherein R.sup.5 represents a hydrogen atom, a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms (the alkyl group has the same meaning as described above in
the definition of R.sup.3) or a straight or branched chain
aliphatic acyl group having from 1 to 8 carbon atoms (the aliphatic
acyl group includes, for example, an alkanoyl group having from 1
to 8 carbon atoms and an alkenoyl group having from 3 to 8 carbon
atoms) or an aromatic acyl group having from 7 to 11 carbon atoms),
the group of the formula: >N--R.sup.5 includes, for example, an
imino, methylimino, ethylimino, propylimino, isopropylimino,
butylimino, isobutylimino, s-butylimino, t-butylimino, pentylimino,
1-methylbutylimino, 2-methylbutylimino, 3-methylbutylimino,
1,1-dimethylpropylimino, 1,2-dimethylpropylimino,
2,2-dimethylpropylimino- , 1-ethylpropylimino, hexylimino,
1-methylpentylimino, 2-methylpentylimino, 3-methylpentylimino,
4-methylpentylimino, 1,1-dimethylbutylimino,
1,2-dimethylbutylimino, 1,3-dimethylbutylimino,
2,2-dimethylbutylimino, 2,3-dimethylbutylimino,
3,3-dimethylbutylimino, 1-ethylbutylimino,
1,1,2-trimethylpropylimino, 1,2,2-trimethylpropylimino- ,
acetylimino, propionylimino, butyrylimino, pentanoylimino,
hexanoylimino, heptanoylimino, octanoylimino, benzoylimino or
p-toluoylimino group;
[0103] preferably an imino group, a straight or branched chain
alkylimino group having from 1 to 4 carbon atoms or an acetylimino
group;
[0104] most preferably an imino, methylimino, ethylimino or
acetylimino group.
[0105] The amidocarboxylic acid derivatives of the formula (I) of
the present invention can be converted to an acid addition salt
according to a conventional method in the case where it has a basic
group. Such salts include salts of hydrohalogenic acids such as
hydrofluoric acid, hydrochloric acid, hydrobromic acid and
hydroiodic acid; inorganic acid salts such as a nitrate,
perchlorate, sulfate and phosphate; salts of lower alkanesulfonic
acids such as methanesulfonic acid, trifluoromethanesulfonic acid
and ethanesulfonic acid; salts of arylsulfonic acid such as
benzenesulfonic acid and p-toluenesulfonic acid; salts of amino
acids such as glutamic acid and aspartic acid; and salts of
carboxylic acids such as acetic acid, fumaric acid, tartaric acid,
oxalic acid, maleic acid, malic acid, succinic acid, benzoic acid,
mandelic acid, ascorbic acid, lactic acid, gluconic acid and citric
acid; preferably salts of hydrohalogenic acids.
[0106] Further, the amidocarboxylic acid derivatives of the formula
(I) can be converted to a metal salt according to a conventional
method since it has a carboxyl group. Such salts include alkali
metal salts such as lithium, sodium and potassium; alkaline earth
metal salts such as calcium, barium and magnesium; and aluminum
salts, preferably alkali metal salts.
[0107] The amidocarboxylic acid derivatives of the formula (I) of
the present invention can be converted to a pharmacologically
acceptable ester according to a conventional method. The
pharmacologically acceptable ester of the amidocarboxylic acid
derivative of the formula (I) is not particularly limited so long
as it can be medically used and pharmacologically accepted in
comparison with the amidocarboxylic acid of the formula (I).
[0108] The esters of the amidocarboxylic acid derivatives of the
formula (I) of the present invention includes a straight or
branched chain alkyl group having from 1 to 6 carbon atoms; an
aralkyl group having from 7 to 19 carbon atoms; a straight or
branched chain alkyl group having from 1 to 5 carbon atoms which is
substituted by a straight or branched chain alkanoyloxy group
having from 1 to 6 carbon atoms; a straight or branched chain alkyl
group having from 1 to 5 carbon atoms which is substituted by a
straight or branched chain alkyloxycarbonyloxy group having from 1
to 6 carbon atoms; a straight or branched chain alkyl group having
from 1 to 5 carbon atoms which is substituted by a
cycloalkylcarbonyloxy group having from 5 to 7 carbon atoms; a
straight or branched chain alkyl group having from 1 to 5 carbon
atoms which is substituted by a cycloalkyloxycarbonyloxy group
having from 5 to 7 carbon atoms; a straight or branched chain alkyl
group having from 1 to 5 carbon atoms which is substituted by an
arylcarbonyloxy group having from 6 to 10 carbon atoms; a straight
or branched chain alkyl group having from 1 to 5 carbon atoms which
is substituted by an aryloxycarbonyloxy group having from 6 to 10
carbon atoms; or a 2-oxo-1,3-dioxolen-4-ylmethyl group having a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms as a substituent at the 5-position.
[0109] The straight or branched chain alkyl group having from 1 to
4 carbon atoms and the straight or branched chain alkyl group
having from 1 to 6 carbon atoms include a methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl,
1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl,
1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl,
1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,
1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,
1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl or
1,2,2-trimethylpropyl group; preferably a straight or branched
chain alkyl group having from 1 to 4 carbon atoms; more preferably
a methyl, ethyl, propyl, isopropyl, butyl or isobutyl group; most
preferably a methyl or ethyl group.
[0110] The aralkyl group having from 7 to 19 carbon atoms includes
a benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl,
1-naphthylmethyl, 2-naphthylmethyl or diphenylmethyl group;
preferably a benzyl group.
[0111] The cycloalkyl group having from 5 to 7 carbon atoms
includes a cyclopentyl, cyclohexyl or cycloheptyl group; preferably
a cyclohexyl group.
[0112] The aryl group having from 6 to 10 carbon atoms includes a
phenyl or naphthyl group; preferably the phenyl group.
[0113] The specific example of the preferable ester residue a
includes a methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
t-butyl, benzyl, acetoxymethyl, 1-(acetoxy)ethyl,
propionyloxymethyl, 1-(propionyloxy)ethyl, butyryloxymethyl,
1-(butyryloxy)ethyl, isobutyryloxymethyl, 1-(isobutyryloxy)ethyl,
valeryloxymethyl, 1-(valeryloxy)ethyl, isovaleryloxymethyl,
1-(isovaleryloxy)ethyl, pivaloyloxymethyl, 1-(pivaloyloxy)ethyl,
methoxycarbonyloxymethyl, 1-(methoxycarbonyloxy)ethyl,
ethoxycarbonyloxymethyl, 1-(ethoxycarbonyloxy)ethyl,
propoxycarbonyloxymethyl, 1-(propoxycarbonyloxy)ethyl,
isopropoxycarbonyloxymethyl, 1-(isopropoxycarbonyloxy)ethyl,
butoxycarbonyloxymethyl, 1-(butoxycarbonyloxy)ethyl,
isobutoxycarbonyloxymethyl, 1-(isobutoxycarbonyloxy)ethyl,
t-butoxycarbonyloxymethyl, 1-(t-butoxycarbonyloxy)ethyl,
cyclopentanecarbonyloxymethyl, 1-(cyclopentanecarbonyloxy)ethyl,
cyclohexanecarbonyloxymethyl, 1-(cyclohexanecarbonyloxy)ethyl,
cyclopentyloxycarbonyloxymethyl,
1-(cyclopentyloxycarbonyloxy)ethyl, cyclohexyloxycarbonyloxymethyl,
1-(cyclohexyloxycarbonyloxy)ethyl, benzoyloxymethyl,
1-(benzoyloxy)ethyl, phenoxycarbonyloxymethyl,
1-(phenoxycarbonyloxy)ethyl or
5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl group.
[0114] Incidentally, the amidocarboxylic acid derivatives of the
formula (I), the pharmacologically acceptable salts thereof or the
pharmacologically acceptable esters thereof have various isomers.
For example, an optical isomer derived from an asymmetric carbon at
the a-position of the carboxylic acid exists. In the formula (I),
all of the stereoisomers based on these asymmetric carbon atoms and
the equivalent and non-equivalent mixtures of these isomers are
shown by a single formula. Therefore, the present invention
includes all of these isomers and a mixture of these isomers.
[0115] Moreover, in the present invention, in the case where the
amidocarboxylic acid derivative of the formula (I), the
pharmacologically acceptable salts thereof and the
pharmacologically acceptable esters thereof form solvates (for
example, hydrates), the present invention includes all of these
solvates.
[0116] Further, the present invention includes all compounds which
are metabolized in living bodies and are converted to the
amidocarboxylic acid derivatives of the formula (I) or a salt
thereof, for example, so-called prodrugs such as amide
derivatives.
[0117] The amidocarboxylic acid derivatives of the formula (I)
preferably include:
[0118] (1) amidocarboxylic acid derivatives in which R.sup.1 is a
hydrogen atom, a straight or branched chain alkyl group having from
1 to 4 carbon atoms or an aralkyl group having from 7 to 9 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0119] (2) amidocarboxylic acid derivatives in which R.sup.1 is a
hydrogen atom or a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0120] (3) amidocarboxylic acid derivatives in which R.sup.1 is a
hydrogen atom or an alkyl group having one or two carbon atoms,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0121] (4) amidocarboxylic acid derivatives in which R.sup.1 is a
hydrogen atom, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0122] (5) amidocarboxylic acid derivatives in which R.sup.2 is a
straight or branched chain alkylene group having from 2 to 5 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0123] (6) amidocarboxylic acid derivatives in which R.sup.2 is a
straight or branched chain alkylene group having from 2 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0124] (7) amidocarboxylic acid derivatives in which R.sup.2 is an
ethylene group, a trimethylene group or a methylethylene group,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0125] (8) amidocarboxylic acid derivatives in which R.sup.2 is an
ethylene group, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0126] (9) amidocarboxylic acid derivatives in which R.sup.3 is a
hydrogen atom, a straight or branched chain alkyl group having from
1 to 4 carbon atoms, an alkoxy group having one or two carbon
atoms, an alkylthio group having one or two carbon atoms, a halogen
atom, a nitro group, a hydroxyl group or a straight or branched
chain aliphatic acyl group having from 1 to 5 carbon atoms,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0127] (10) amidocarboxylic acid derivatives in which R.sup.3 is a
hydrogen atom, a halogen atom or a nitro group, pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0128] (11) amidocarboxylic acid derivatives in which R.sup.3 is a
hydrogen atom, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0129] (12) amidocarboxylic acid derivatives in which R.sup.4 is a
hydrogen atom or a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0130] (13) amidocarboxylic acid derivatives in which R.sup.4 is a
hydrogen atom or an alkyl group having one or two carbon atoms,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0131] (14) amidocarboxylic acid derivatives in which R.sup.4 is a
hydrogen atom or a methyl group, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0132] (15) amidocarboxylic acid derivatives in which R.sup.4 is a
hydrogen atom, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0133] (16) amidocarboxylic acid derivatives in which R.sup.4 is a
methyl group, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0134] (17) amidocarboxylic acid derivatives in which Z is a
straight or branched chain alkylene group having from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0135] (18) amidocarboxylic acid derivatives in which Z is an
alkylene group having one or two carbon atoms, pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0136] (19) amidocarboxylic acid derivatives in which Z is a
methylene group, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0137] (20) amidocarboxylic acid derivatives in which W represents
(i) a straight or branched chain alkyl group having from 1 to 6
carbon atoms, (ii) a hydroxyl group, (iii) a straight or branched
chain alkoxy group having from 1 to 4 carbon atoms, (iv) a straight
or branched chain alkylthio group having from 1 to 4 carbon atoms,
(v) an aryl group having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.1 described later, (vi) an
aryloxy group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha..sup.1 described later on the aryl
moiety, (vii) an arylthio group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.1 described
later on the aryl moiety, (viii) an aralkyl group having from 7 to
12 carbon atoms which may have from 1 to 3 substituents
.alpha..sup.1 described later on the aryl moiety, (ix) an
aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.1 described later on the aryl
moiety, (x) an aralkylthio group having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.1 described
later on the aryl moiety, (xi) an aryloxyalkyl group in which the
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.1 described later and
the alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (xii) a mono- or dicyclic, 5- to
10-membered hetero aryl group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom, (xiii) a mono- or dicyclic, 5- to 10-membered
hetero aryloxy group containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, nitrogen atom and
sulfur atom, (xiv) a mono- or dicyclic, 5- to 10-membered hetero
arylthio group containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, nitrogen atom and sulfur
atom or (xv) a mono- or dicyclic, 5- to 10-membered saturated
heterocyclic group containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, nitrogen atom and
sulfur atom,
[0138] here, the substituent .alpha..sup.1 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents .beta..sup.1
described later, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups,
(xvi) straight or branched chain monoalkylamino groups in which the
alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or
branched chain alkoxycarbonylamino groups in which the alkoxy
moiety has from 1 to 4 carbon atoms, (xviii)
aralkyloxycarbonylamino groups in which the aralkyl moiety has from
7 to 12 carbon atoms, (xix) straight or branched chain dialkylamino
groups in which each alkyl group may be the same or different and
each has from 1 to 4 carbon atoms, (xx) aralkyl groups having from
7 to 12 carbon atoms which may have from 1 to 3 substituents
.beta..sup.1 described later on the aryl moiety, (xxi) aryl groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta..sup.1, which may be the same or different,
described later, (xxii) aryloxy groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .beta..sup.1
described later on the aryl moiety, (xxiii) arylthio groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
.beta..sup.1 described later on the aryl moiety, (xxiv)
arylsulfonyl groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents .beta..sup.1 described later on the aryl
moiety, (xxv) arylsulfonylamino groups having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .beta..sup.1
described later on the aryl moiety (the nitrogen atom of the amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxvi) mono- or dicyclic,
5- to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxvii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxviii) mono- or
dicyclic, 5- to 10-membered hetero arylthio groups containing from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxix) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonyl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .beta..sup.1 described later, (xxx) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonylamino groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta..sup.1 described later on
the hetero aryl moiety (the nitrogen atom of the amino moiety may
be substituted with a straight or branched chain alkyl having from
1 to 6 carbon atoms) and (xxxi) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0139] here, the substituent .beta..sup.1 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) amino groups, (xiv) straight or
branched chain monoalkylamino groups in which the alkyl moiety has
from 1 to 4 carbon atoms, (xv) straight or branched chain
dialkylamino groups in which each alkyl moiety may be the same or
different and each has from 1 to 4 carbon atoms, (xvi) straight or
branched chain aminoalkyl groups having from 1 to 4 carbon atoms,
(xvii) monoalkylaminoalkyl groups in which the monoalkylamino
moiety has one straight or branched chain alkyl group having from 1
to 4 carbon atoms and the alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms, (xviii)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which the alkoxy moiety has from 1 to 4 carbon atoms or (xx)
aralkyloxycarbonylamino groups in which the aryl moiety has from 6
to 10 carbon atoms and the alkyl moiety has from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof and
pharmacologically acceptable esters thereof;
[0140] (21) amidocarboxylic acid derivatives in which W represents
(i) a straight or branched chain alkyl group having from 1 to 6
carbon atoms, (ii) a hydroxyl group, (iii) a straight or branched
chain alkoxy group having from 1 to 4 carbon atoms, (iv) a straight
or branched chain alkylthio group having from 1 to 4 carbon atoms,
(v) an aryl group having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.2 described later, (vi) an
aryloxy group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha..sup.2 described later on the aryl
moiety, (vii) an arylthio group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.2 described
later on the aryl moiety, (viii) an aralkyl group having from 7 to
12 carbon atoms which may have from 1 to 3 substituents
.alpha..sup.2 described later on the aryl moiety, (ix) an
aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.2 described later on the aryl
moiety, (x) an aralkylthio group having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.2 described
later on the aryl moiety, (xi) an aryloxyalkyl group in which the
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.2 described later and
the alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (xii) a mono- or dicyclic, 5- to
10-membered hetero aryloxy group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom or (xiii) a mono- or dicyclic, 5- to
10-membered hetero arylthio group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0141] here, the substituent .alpha..sup.2 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (xiii) aryl groups having from 6 to 10 carbon atoms
which may be the same or different and have from 1 to 3
substituents .beta..sup.2 described later, (xiv) aryloxy groups
having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta..sup.2 described later on the aryl moiety, (xv)
arylthio groups having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents .beta..sup.2 described later on the aryl
moiety, (xvi) mono- or dicyclic, 5- to 10-membered hetero aryl
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta..sup.2 described later,
(xvii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta..sup.2 described later,
(xviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta..sup.2 described later and
(xix) mono- or dicyclic, 5- to 10-membered saturated heterocyclic
groups containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom,
[0142] here, the substituent .beta..sup.2 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms or (x) dialkylaminoalkyl groups in which
the dialkylamino moiety has two straight or branched chain alkyls
groups having from 1 to 4 carbon atoms which may be the same or
different and the alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0143] (22) amidocarboxylic acid derivatives in which W represents
(i) a straight or branched chain alkyl group having from 1 to 6
carbon atoms, (ii) a straight or branched chain alkoxy group having
from 1 to 4 carbon atoms, (iii) an aryloxy group having from 6 to
10 carbon atoms which may have from 1 to 3 substituents
.alpha..sup.3 described later on the aryl moiety, (iv) an arylthio
group having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha..sup.3 described later on the aryl moiety, (v)
an aralkyl group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.3 described later on the aryl
moiety, (vi) an aralkyloxy group having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.3 described
later on the aryl moiety, (vii) an aryloxyalkyl group in which the
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.3 described later and
the alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (viii) a mono- or dicyclic, 5- to
10-membered hetero aryloxy group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom or (ix) a mono- or dicyclic, 5- to
10-membered hetero arylthio group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0144] here, the substituent .alpha..sup.3 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0145] (23) amidocarboxylic acid derivatives in which W represents
(i) a straight or branched chain alkyl group having from 1 to 6
carbon atoms, (ii) a straight or branched chain alkoxy group having
from 1 to 4 carbon atoms, (iii) a phenoxy group which may have from
1 to 3 substituents .alpha..sup.4 described later on the phenyl
moiety, (iv) a phenylthio group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.4 described
later on the phenyl moiety, (v) an aralkyl group having from 7 to
10 carbon atoms, (vi) an aralkyloxy group having from 7 to 10
carbon atoms, (vii) an aryloxyalkyl group in which the aryl moiety
has from 6 to 10 carbon atoms and the alkyl moiety is straight or
branched chain and has from 1 to 4 carbon atoms, (viii) a mono- or
dicyclic, 5- to 10-membered hetero aryloxy group containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom or (ix) a mono- or dicyclic, 5-
to 10-membered hetero arylthio group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0146] here, the substituent .alpha..sup.4 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having one or two
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having one or two carbon atoms, (vii) halogen atoms, (viii) cyano
groups or (ix) pyridyl groups, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0147] (24) amidocarboxylic acid derivatives in which W represents
a phenoxy group which may have one substituent .alpha..sup.5
described below on the phenyl moiety,
[0148] here, the substituent .alpha..sup.5 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms (v)
straight or branched chain alkylthio groups having one or two
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from one or two carbon atoms, (vii) halogen atoms, (viii)
cyano groups or (ix) pyridyl groups, pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof;
[0149] (25) amidocarboxylic acid derivatives in which W represents
a phenoxy group which may have one substituent .alpha..sup.6
described below on the phenyl moiety,
[0150] here, the substituent .alpha..sup.6 represents a group
selected from the group consisting of methyl, ethyl, isopropyl,
t-butyl, trifluoromethyl, methoxy and trifluoromethoxy groups, and
fluorine atoms and chlorine atoms, pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof;
[0151] (26) amidocarboxylic acid derivatives in which W represents
a phenoxy, methylphenoxy, ethylphenoxy, isopropylphenoxy,
t-butylphenoxy, trifluoromethylphenoxy, methoxyphenoxy,
trifluoromethoxyphenoxy, fluorophenoxy or chlorophenoxy group,
pharmaceutically acceptable salts thereof or pharmaceutically
acceptable esters thereof,
[0152] (27) amidocarboxylic acid derivatives in which X represents
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha..sup.7 described below or a mono- or
dicyclic, 5- to 10-membered hetero aryl group containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .alpha..sup.7 described below,
[0153] here, the substituent .alpha..sup.7 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents .beta..sup.3
described later, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (xiv) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents .beta..sup.3
described below, (xv) phenyl groups which may have from 1 to 3
substituents .beta..sup.3 described below, (xvi) phenoxy groups
which may have from 1 to 3 substituents .beta..sup.3 described
below, (xvii) phenylthio groups which may have from 1 to 3
substituents .beta..sup.3 described below, (xviii) phenylsulfonyl
groups which may have from 1 to 3 substituents .beta..sup.3
described below, (xix) phenylsulfonylamino groups which may have
from 1 to 3 substituents .beta..sup.3 described below on the phenyl
moiety (the nitrogen atom of the amino moiety may be substituted
with a straight or branched chain alkyl group having from 1 to 6
carbon atoms), (xx) furyl groups, (xxi) thienyl groups, (xxii)
oxazolyl groups, (xxiii) isoxazolyl groups, (xxiv) thiazolyl
groups, (xxv) pyridyl groups which may have from 1 to 3
substituents .beta..sup.3 described below, (xxvi) pyridyloxy groups
which may have from 1 to 3 substituents .beta..sup.3 described
below, (xxvii) pyridylthio groups which may have from 1 to 3
substituents .beta..sup.3 described below, (xxviii) pyridylsulfonyl
groups which may have from 1 to 3 substituents .beta..sup.3
described below, (xxix) imidazolyl groups (the nitrogen atom of the
ring may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxx) pyridylsulfonylamino
groups which may have from 1 to 3 substituents .beta..sup.3
described below on the pyridyl moiety (the nitrogen atom of the
amino moiety may be substituted with a straight or branched chain
alkyl group having from 1 to 6 carbon atoms) and (xxxi) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom,
[0154] here, the substituent .beta..sup.3 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0155] (28) amidocarboxylic acid derivatives in which X represents
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha..sup.8 described below or a mono- or
dicyclic, 5- to 10-membered hetero aryl group containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .alpha..sup.8 described below,
[0156] here, the substituent .alpha..sup.8 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms, (x) phenyl groups which may have from 1 to 3
substituents .beta..sup.4 described below, (xi) phenoxy groups
which may have from 1 to 3 substituents .beta..sup.4 described
below, (xii) phenylthio groups which may have from 1 to 3
substituents .beta..sup.4 described below, (xiii) furyl groups,
(xiv) thienyl groups, (xv) oxazolyl groups, (xvi) isoxazolyl
groups, (xvii) thiazolyl groups, (xviii) pyridyl groups which may
have from 1 to 3 substituents .beta..sup.4 described below, (xix)
imidazolyl groups (the nitrogen atom of the ring may be substituted
with a straight or branched chain alkyl group having from 1 to 6
carbon atoms) and (xx) mono- or dicyclic, 5- to 10-membered
saturated heterocyclic groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom,
[0157] here, the substituent .beta..sup.4 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0158] (29) amidocarboxylic acid derivatives in which X represents
an aryl group having from 6 to 10 carbon atoms which may have from
1 to 3 substituents .alpha..sup.9 described below or a mono- or
dicyclic, 5- to 10-membered hetero aryl group containing from 1 to
4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .alpha..sup.9 described below,
[0159] here, the substituent .alpha..sup.9 represents a group
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents .beta..sup.5 described
below (vi) phenoxy groups which may have from 1 to 3 substituents
.beta..sup.5 described below, (vii) pyridyl groups which may have
from 1 to 3 substituents .beta..sup.5 described below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom,
[0160] here, the substituent .beta..sup.5 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain hydroxyalkyl groups having from 1 to 4 carbon
atoms, (vi) halogen atoms, (vii) nitro groups, (viii) formyl
groups, (ix) carboxyl groups, (x) straight or branched chain
dialkylamino groups in which each alkyl may be the same or
different and each has from 1 to 4 carbon atoms and (xi)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0161] (30) amidocarboxylic acid derivatives in which X represents
a phenyl, naphthyl, imidazolyl, oxazolyl, pyridyl, indolyl,
quinolyl or isoquinolyl group which may have from 1 to 3
substituents .alpha..sup.10 described below;
[0162] here, the substituent .alpha..sup.10 represents the group
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups which may be the same or different and in which
each alkyl group has from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents .beta..sup.6 described
below, (vi) phenoxy groups which may have from 1 to 3 substituents
.beta..sup.6 described below, (vii) pyridyl groups which may have
from 1 to 3 substituents .beta..sup.6 described below and (viii) 5-
to 10- membered saturated heterocyclic groups of one ring or two
rings containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, the nitrogen atom and the sulfur
atom,
[0163] here, the substituent .beta..sup.6 represents the group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain hydroxyalkyl groups having from 1 to 4 carbon
atoms, (vi) halogen atoms, (vii) nitro groups, (viii) formyl
groups, (ix) carboxyl groups, (x) straight or branched chain
dialkylamino groups which may be the same or different and in which
each alkyl groups has from 1 to 4 carbon atoms and (xi)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, pharmaceutically acceptable salts thereof or
pharmaceutically acceptable esters thereof;
[0164] (31) amidocarboxylic acid derivatives in which X represents
a phenyl, indolyl, pyridyl or quinolyl group, which may have from 1
to 3 substituents .alpha..sup.11 described below. here, the
substituent .alpha..sup.11 represents a group selected from the
group consisting of (i) hydroxyl groups, (ii) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (iii) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (iv) straight or branched chain dialkylamino groups
in which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (v) phenyl groups which may have from 1
to 3 substituents .beta..sup.7 described below, (vi) phenoxy groups
which may have from 1 to 3 substituents .beta..sup.7 described
below, (vii) pyridyl groups which may have from 1 to 3 substituents
.beta..sup.7 described below and (viii) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0165] here, the substituent .beta..sup.7 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain hydroxyalkyl groups having from 1 to 4 carbon
atoms, (vi) halogen atoms, (vii) nitro groups, (viii) formyl
groups, (ix) carboxyl groups, (x) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xi)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0166] (32) amidocarboxylic acid derivatives in which X represents
a phenyl group which may have one substituent .alpha..sup.12
described below,
[0167] here, the substituent .alpha..sup.12 represents a group
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups (the phenyl moiety may be substituted
with 1 to 3 substituents, which may be the same or different,
including methyl, ethyl, trifluoromethyl, hydroxyl, methoxy,
ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups), phenoxy, phenylthio,
phenylsufonyl, phenylsulfonylamino, N-methylphenylsulfonylamino and
pyridyl groups (the pyridyl moiety may be substituted with a
methyl, ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy or
trifluoromethoxy group, a fluorine atom, a chlorine atom, or a
nitro, dimethylamino or diethylamino group), pyridyloxy,
pyridylthio, pyridylsulfonyl and piperidyl groups, or
[0168] X represents a pyridyl group which may have one substituent
.alpha..sup.13 described below,
[0169] here, the substituent .alpha..sup.13 represents a group
selected from the group consisting of methyl, isopropyl, methoxy,
ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropoxy and benzyloxy
groups, alkylthio groups having one or two carbon atoms,
alkylsulfonyl groups having one or two carbon atoms, benzyl groups,
phenyl groups (the phenyl moiety may be substituted with a methyl,
ethyl, trifluoromethyl, methoxy, ethoxy or isopropoxy group, a
fluorine atom, a chlorine atom, or a nitro, dimethylamino or
diethylamino group), phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino and N-methylphenylsulfonylamino groups,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0170] (33) amidocarboxylic acid derivatives in which X represents
a phenyl group which may have one substituent .alpha..sup.12
described below,
[0171] here, the substituent .alpha..sup.12 represents a group
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups (the phenyl moiety may be substituted
with 1 to 3 substituents, which may be the same or different,
including methyl, ethyl, trifluoromethyl, hydroxyl, methoxy,
ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms, nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups), phenoxy, phenylthio,
phenylsufonyl, phenylsulfonylamino and N-methylphenylsulfonylamino
groups, pyridyl groups (the pyridyl moiety may be substituted with
a methyl, ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, or
trifluoromethoxy group, a fluorine atom, a chlorine atom, or a
nitro, dimethylamino or diethylamino group), pyridyloxy,
pyridylthio, pyridylsulfonyl and piperidyl groups,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0172] (34) amidocarboxylic acid derivatives in which X represents
a pyridyl group which may have one substituent .alpha..sup.13
described below,
[0173] here, the substituent .alpha..sup.13 represents a group
selected from the group consisting of methyl, isopropyl, methoxy,
ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropoxy and benzyloxy
groups, alkylthio groups having one or two carbon atoms,
alkylsulfonyl groups having one or two carbon atoms, benzyl groups,
phenyl groups (the phenyl moiety may be substituted with a methyl,
ethyl, trifluoromethyl, methoxy, ethoxy or isopropoxy group, a
fluorine atom, a chlorine atom, or a nitro, dimethylamino or
diethylamino group), phenoxy, phenylthio, phenylsufonyl,
phenylsulfonylamino and N-methylphenylsulfonylamino groups,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0174] (35) amidocarboxylic acid derivatives in which X represents
a 2,2,3,3-tetrafluoropropoxypyridyl group or a phenylpyridyl group
(the phenyl moiety may be substituted with a methyl, ethyl,
trifluoromethyl, methoxy, ethoxy or isopropoxy group, a fluorine
atom, a chlorine atom, or a nitro, dimethylamino or diethylamino
group), pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0175] (36) amidocarboxylic acid derivatives in which X represents
a biphenylyl group (each phenyl moiety may be substituted with one
substituent, which may be the same or different, including a
methyl, trifluoromethyl, hydroxyl, methoxy or hydroxymethyl group,
a fluorine atom, a chlorine atom, or a formyl, carboxyl, nitro,
dimethylamino or N,N-dimethylaminomethyl group), a pyridylphenyl
group (the pyridyl moiety may be substituted with one substituent
including a methyl, ethyl, trifluoromethyl, methoxy, ethoxy,
isopropoxy or trifluoromethoxy group, a fluorine atom, a chlorine
atom, or a nitro, dimethylamino or diethylamino group) or a
phenylpyridyl group (the phenyl moiety may be substituted with one
substituent including a methyl, ethyl, trifluoromethyl, methoxy,
ethoxy or isopropoxy group, a fluorine atom, a chlorine atom, a
nitro group or a dimethylamino group), pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof;
[0176] (37) amidocarboxylic acid derivatives in which X represents
a biphenylyl, (methylphenyl)phenyl, (trifluoromethylphenyl)phenyl,
(hydroxyphenyl)phenyl, (methoxyphenyl)phenyl,
(hydroxymethylphenyl)phenyl- , (fluorophenyl)phenyl,
(chlorophenyl)phenyl, (formylphenyl)phenyl, (carboxyphenyl)phenyl,
(nitrophenyl)phenyl, (dimethylaminophenyl)phenyl or
(N,N-dimethylaminomethylphenyl)phenyl group, pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0177] (38) amidocarboxylic acid derivatives in which X represents
a biphenylyl, (methylphenyl)phenyl, (trifluoromethylphenyl)phenyl,
(methoxyphenyl)phenyl, (fluorophenyl)phenyl or (chlorophenyl)phenyl
group, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0178] (39) amidocarboxylic acid derivatives in which X represents
a biphenylyl, (fluorophenyl)phenyl or (chlorophenyl)phenyl group,
pharmacologically acceptable salts thereof or pharmacologically
acceptable esters thereof;
[0179] (40) amidocarboxylic acid derivatives in which X represents
a pyridylphenyl group (the pyridyl moiety may have one methyl,
ethyl, trifluoromethyl, methoxy, ethoxy or isopropoxy group, a
fluorine atom, a chlorine atom, or a nitro, dimethylamino or
diethylamino group), pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0180] (41) amidocarboxylic acid derivatives in which X represents
a pyridylphenyl, (methylpyridyl)phenyl, (methoxypyridyl)phenyl or
(dimethylaminopyridyl)phenyl group, pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof;
[0181] (42) amidocarboxylic acid derivatives in which X represents
a phenylpyridyl group (the phenyl moiety may have one methyl,
ethyl, methoxy, ethoxy or isopropoxy group, a fluorine atom, a
chlorine atom or a dimethylamino group), pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0182] (43) amidocarboxylic acid derivatives in which X represents
a phenylpyridyl, (methoxyphenyl)pyridyl or (fluorophenyl)pyridyl
group, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof;
[0183] (44) amidocarboxylic acid derivatives in which Y represents
a single bond, an oxygen atom, a sulfur atom or a group of the
formula: >N--R.sup.5 (wherein R.sup.5 represents a hydrogen
atom, a straight or branched chain alkyl group having one or two
carbon atoms or a straight or branched chain aliphatic acyl group
having from 2 to 5 carbon atoms), pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof;
[0184] (45) amidocarboxylic acid derivatives in which Y represents
a single bond or an oxygen atom, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0185] (46) amidocarboxylic acid derivatives in which Y represents
an oxygen atom, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof.
[0186] Further, compounds in which R.sup.1 is selected from (1) to
(4), R.sup.2 is selected from (5) to (8), R.sup.3 is selected from
(9) to (11), R.sup.4 is selected from (12) to (16), Z is selected
from (17) to (19), W is selected from (20) to (26), X is selected
from (27) to (43), and Y is selected from (44) to (46) to be
combined with one another are preferable.
[0187] For example, the phenylalkylcarboxylic acid of the formula
(I) includes:
[0188] (47) amidocarboxylic acid derivatives in which
[0189] R.sup.1 is a hydrogen atom, a straight or branched chain
alkyl group having from 1 to 4 carbon atoms or an aralkyl group
having from 7 to 9 carbon atoms;
[0190] R.sup.2 is a straight or branched chain alkylene group
having from 2 to 4 carbon atoms;
[0191] R.sup.3 is a hydrogen atom, a straight or branched chain
alkyl group having from 1 to 4 carbon atoms, an alkoxy group having
one or two carbon atoms, an alkylthio group having one or two
carbon atoms, a halogen atom, a nitro group, a hydroxyl group or a
straight or branched chain aliphatic acyl group having from 1 to 5
carbon atoms;
[0192] R.sup.4 is a hydrogen atom or a straight or branched chain
alkyl group having from 1 to 4 carbon atoms;
[0193] Z is a straight or branched chain alkylene group having from
1 to 4 carbon atoms;
[0194] W represents (i) a straight or branched chain alkyl group
having from 1 to 6 carbon atoms, (ii) a hydroxyl group, (iii) a
straight or branched chain alkoxy group having from 1 to 4 carbon
atoms, (iv) a straight or branched chain alkylthio group having
from 1 to 4 carbon atoms, (v) an aryl group having from 6 to 10
carbon atoms which may have from 1 to 3 substituents .alpha..sup.1
described later, (vi) an aryloxy group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .alpha..sup.1
described later on the aryl moiety, (vii) an arylthio group having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
.alpha..sup.1 described later on the aryl moiety, (viii) an aralkyl
group having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha..sup.1 described later on the aryl moiety, (ix)
an aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.1 described later on the aryl
moiety, (x) an aralkylthio group having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.1 described
later on the aryl moiety, (xi) an aryloxyalkyl group in which the
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.1 described later and
the alkyl moiety is a straight or branched chain alkyl group having
from 1 to 4 carbon atoms, (xii) a mono- or dicyclic, 5- to
10-membered hetero aryl group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom, (xiii) a mono- or dicyclic, 5- to 10-membered
hetero aryloxy group containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, nitrogen atom and
sulfur atom, (xiv) a mono- or dicyclic, 5- to 10-membered hetero
arylthio group containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, a nitrogen atom and a
sulfur atom or (xv) a mono- or dicyclic, 5- to 10-membered
saturated heterocyclic group containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom,
[0195] here, the substituent .alpha..sup.1 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have 1 to 3 substituents .beta..sup.1 described
later, (x) straight or branched chain alkylthio groups having from
1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl
groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii)
nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight
or branched chain monoalkylamino groups in which the alkyl moiety
has from 1 to 4 carbon atoms, (xvii) straight or branched chain
alkoxycarbonylamino groups in which the alkoxy moiety has from 1 to
4 carbon atoms, (xviii) aralkyloxycarbonylamino groups in which the
aralkyl moiety has from 7 to 12 carbon atoms, (xix) straight or
branched chain dialkylamino groups in which each alkyl group may be
the same or different and each has from 1 to 4 carbon atoms, (xx)
aralkyl groups having from 7 to 12 carbon atoms which may have from
1 to 3 substituents .beta..sup.1 described later on the aryl
moiety, (xxi) aryl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .beta..sup.1, which may be the
same or different described later, (xxii) aryloxy groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
.beta..sup.1 described later on the aryl moiety, (xxiii) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta..sup.1 described later on the aryl moiety,
(xxiv) arylsulfonyl groups having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .beta..sup.1 described later on
the aryl moiety, (xxv) arylsulfonylamino groups having from 6 to 10
carbon atoms which may have from 1 to 3 substituents .beta..sup.1
described later on the aryl moiety (the nitrogen atom of the amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xxvi) mono- or dicyclic,
5- to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxvii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxviii) mono- or
dicyclic, 5- to 10-membered hetero arylthio groups containing from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.1 described later, (xxix) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonyl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .beta..sup.1 described later, (xxx) mono- or
dicyclic, 5- to 10-membered hetero arylsulfonylamino groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .beta..sup.1 described later on
the hetero aryl moiety (the nitrogen atom of the amino moiety may
be substituted with a straight or branched chain alkyl group having
from 1 to 6 carbon atoms) and (xxxi) mono- or dicyclic, 5- to
10-membered saturated heterocyclic groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0196] here, the substituent .beta..sup.1 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) amino groups, (xiv) straight or
branched chain monoalkylamino groups in which the alkyl moiety has
from 1 to 4 carbon atoms, (xv) straight or branched chain
dialkylamino groups in which each alkyl moiety may be the same or
different and each has from 1 to 4 carbon atoms, (xvi) straight or
branched chain aminoalkyl groups having from 1 to 4 carbon atoms,
(xvii) monoalkylaminoalkyl groups in which the monoalkylamino
moiety has one straight or branched chain alkyl group having from 1
to 4 carbon atoms and the alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms, (xxviii)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms, (xix) straight or branched chain alkoxycarbonylamino groups
in which the alkoxy moiety is a straight or branched chain alkoxy
group having from 1 to 4 carbon atoms and (xx)
aralkyloxycarbonylamino groups in which the aryl moiety has from 6
to 10 carbon atoms and the alkyl moiety has from 1 to 4 carbon
atoms;
[0197] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.7 described
later or a mono- or dicyclic, 5- to 10-membered hetero aryl group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .alpha..sup.7 described
below,
[0198] here, the substituent .alpha..sup.7 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain aliphatic acyl groups having from 1 to 5
carbon atoms, (vi) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (vii) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon
atoms which may have from 1 to 3 substituents .beta..sup.3
described later, (x) straight or branched chain alkylthio groups
having from 1 to 4 carbon atoms, (xi) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen
atoms, (xiii) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms, (xiv) aralkyl groups having from 7 to 12
carbon atoms which may have from 1 to 3 substituents .beta..sup.3
described later, (xv) phenyl groups which may have from 1 to 3
substituents .beta..sup.3 described later, (xvi) phenoxy groups
which may have from 1 to 3 substituents .beta..sup.3 described
later, (xvii) phenylthio groups which may have from 1 to 3
substituents .beta..sup.3 described later, (xviii) phenylsulfonyl
groups which may have from 1 to 3 substituents .beta..sup.3
described later on the phenyl moiety, (xix) phenylsulfonylamino
groups which may have from 1 to 3 substituents .beta..sup.3
described later on the phenyl moiety (the nitrogen atom of the
amino moiety may be substituted with a straight or branched chain
alkyl group having from 1 to 6 carbon atoms), (xx) furyl groups,
(xxi) thienyl groups, (xxii) oxazolyl groups, (xxiii) isoxazolyl
groups, (xxiv) thiazolyl groups, (xxv) pyridyl groups which may
have from 1 to 3 substituents .beta..sup.3 described later, (xxvi)
pyridyloxy groups which may have from 1 to 3 substituents
.beta..sup.3 described later, (xxvii) pyridylthio groups which may
have from 1 to 3 substituents .beta..sup.3 described later,
(xxviii) pyridylsulfonyl groups which may have from 1 to 3
substituents .beta..sup.3 described later, (xxix) imidazolyl groups
(the nitrogen atom of the ring may be substituted with a straight
or branched chain alkyl group having from 1 to 6 carbon atoms),
(xxx) pyridylsulfonylamino groups which may have from 1 to 3
substituents .beta..sup.3 described later on the pyridyl moiety
(the nitrogen atom of the amino moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms) and (xxxi) mono- or dicyclic, 5- to 10-membered saturated
heterocyclic groups containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, nitrogen atom and
sulfur atom,
[0199] here, the substituent .beta..sup.3 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino group in which each alkyl group may be the same or
different and each has from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and
[0200] Y is a single bond or an oxygen atom, pharmacologically
acceptable salts thereof or pharmacologically acceptable esters
thereof;
[0201] (48) amidocarboxylic acid derivatives in which
[0202] R.sup.1 is a hydrogen atom, a straight or branched chain
alkyl group having from 1 to 4 carbon atoms or an aralkyl group
having from 7 to 9 carbon atoms;
[0203] R.sup.2 is a straight or branched chain alkylene group
having from 2 to 4 carbon atoms;
[0204] R.sup.3 is a hydrogen atom, a halogen atom or a nitro
group;
[0205] R.sup.4 is a hydrogen atom or a straight or branched chain
alkyl group having from 1 to 4 carbon atoms;
[0206] Z is a methylene group;
[0207] W represents (i) a straight or branched chain alkyl group
having from 1 to 6 carbon atoms, (ii) a hydroxyl group, (iii) a
straight or branched chain alkoxy group having from 1 to 4 carbon
atoms, (iv) a straight or branched chain alkylthio group having
from 1 to 4 carbon atoms (v) an aryl group having from 6 to 10
carbon atoms which may have from 1 to 3 substituents .alpha..sup.2
described later, (vi) an aryloxy group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .alpha..sup.2
described later on the aryl moiety, (vii) an arylthio group having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
.alpha..sup.2 described later on the aryl moiety, (viii) an aralkyl
group having from 7 to 12 carbon atoms which may have from 1 to 3
substituents .alpha..sup.2 described later on the aryl moiety, (ix)
an aralkyloxy group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.2 described later on the aryl
moiety, (x) an aralkylthio group having from 7 to 12 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.2 described
later on the aryl moiety, (xi) an aryloxyalkyl group in which the
aryl moiety is an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.2 described later and
the alkyl moiety is a straight or branched chain alkyl having from
1 to 4 carbon atoms, (xii) a mono- or dicyclic, 5- to 10-membered
hetero aryloxy group containing from 1 to 4 hetero atoms selected
from the group consisting of an oxygen atom, nitrogen atom and
sulfur atom or (xiii) a mono- or dicyclic, 5- to 10-membered hetero
arylthio group containing from 1 to 4 hetero atoms selected from
the group consisting of an oxygen atom, nitrogen atom and sulfur
atom,
[0208] here, the substituent .alpha..sup.2 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) straight
or branched chain alkylsulfonyl groups having from 1 to 4 carbon
atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups,
(xii) straight or branched chain dialkylamino groups in which each
alkyl group may be the same or different and each has from 1 to 4
carbon atoms, (xiii) aryl groups having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .beta..sup.2, which may be
the same or different, described later, (xiv) aryloxy groups having
from 6 to 10 carbon atoms which may have from 1 to 3 substituents
.beta..sup.2 described later on the aryl moiety, (xv) arylthio
groups having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .beta..sup.2 described later on the aryl moiety, (xvi)
mono- or dicyclic, 5- to 10-membered hetero aryl groups containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .beta..sup.2 described later, (xvii) mono- or
dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1
to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.2 described later, (xviii) mono- or
dicyclic, 5- to 10-membered hetero arylthio groups containing from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom which may have from 1 to 3
substituents .beta..sup.2 described later and (xix) mono- or
dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom,
[0209] here, the substituent .beta..sup.2 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (v) halogen
atoms, (vi) nitro groups, (vii) formyl groups, (viii) carboxyl
groups, (ix) straight or branched chain dialkylamino groups in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms and (x) dialkylaminoalkyl groups in which
the dialkylamino moiety has two straight or branched chain alkyl
groups having from 1 to 4 carbon atoms which may be the same or
different and the alkyl moiety is a straight or branched chain
alkyl group having from 1 to 4 carbon atoms;
[0210] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.8 described
below or a mono- or dicyclic, 5- to 10-membered hetero aryl group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .alpha..sup.8 described
below,
[0211] here, the substituent .alpha..sup.8 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (vi) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
alkylthio groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) straight or branched chain dialkylamino groups in which
each alkyl group may be the same or different and each has from 1
to 4 carbon atoms, (x) phenyl groups which may have from 1 to 3
substituents .beta..sup.4 described later, (xi) phenoxy groups
which may have from 1 to 3 substituents .beta..sup.4 described
later, (xii) phenylthio groups which may have from 1 to 3
substituents .beta..sup.4 described later, (xiii) furyl groups,
(xiv) thienyl groups, (xv) oxazolyl groups, (xvi) isoxazolyl
groups, (xvii) thiazolyl groups, (xviii) pyridyl groups which may
have from 1 to 3 substituents .beta..sup.4 described later, (xix)
imidazolyl groups (the nitrogen atom of the ring may be substituted
with a straight or branched chain alkyl group having from 1 to 6
carbon atoms) and (xx) mono- or dicyclic, 5- to 10-membered
saturated heterocyclic groups containing from 1 to 4 hetero atoms
selected from the group consisting of an oxygen atom, nitrogen atom
and sulfur atom,
[0212] here, the substituent .beta..sup.4 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain halogenated alkoxy groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylenedioxy groups
having from 1 to 4 carbon atoms, (vii) straight or branched chain
hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) halogen
atoms, (ix) nitro groups, (x) formyl groups, (xi) cyano groups,
(xii) carboxyl groups, (xiii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms and (xiv)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and
[0213] Y is an oxygen atom, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof,
[0214] (49) amidocarboxylic acid derivatives in which
[0215] R.sup.1 is a hydrogen atom, a straight or branched chain
alkyl group having from 1 to 4 carbon atoms or an aralkyl group
having from 7 to 9 carbon atoms;
[0216] R.sup.2 is a straight or branched chain alkylene group
having from 2 to 4 carbon atoms;
[0217] R.sup.3 is a hydrogen atom, a halogen atom or a nitro
group;
[0218] R.sup.4 is a hydrogen atom or a straight or branched chain
alkyl group having from 1 to 4 carbon atoms;
[0219] Z is a methylene group;
[0220] W represents (i) a straight or branched chain alkyl group
having from 1 to 6 carbon atoms, (ii) a straight or branched chain
alkoxy group having from 1 to 4 carbon atoms, (iii) an aryloxy
group having from 6 to 10 carbon atoms which may have from 1 to 3
substituents .alpha..sup.3 described later on the aryl moiety, (iv)
an arylthio group having from 6 to 10 carbon atoms which may have
from 1 to 3 substituents .alpha..sup.3 described later on the aryl
moiety, (v) an aralkyl group having from 7 to 12 carbon atoms which
may have from 1 to 3 substituents .alpha..sup.3 described later on
the aryl moiety, (vi) an aralkyloxy group having from 7 to 12
carbon atoms which may have from 1 to 3 substituents .alpha..sup.3
described later on the aryl moiety, (vii) an aryloxyalkyl group in
which the aryl moiety is an aryl group having from 6 to 10 carbon
atoms which may have from 1 to 3 substituents .alpha..sup.3
described later and the alkyl moiety is a straight or branched
chain alkyl group having from 1 to 4 carbon atoms, (viii) a mono-
or dicyclic, 5- to 10-membered hetero aryloxy group containing from
1 to 4 hetero atoms selected from the group consisting of an oxygen
atom, nitrogen atom and sulfur atom or (ix) a mono- or dicyclic, 5-
to 10-membered hetero arylthio group containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom,
[0221] here, the substituent .alpha..sup.3 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having from 1 to 4
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having from 1 to 4 carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups;
[0222] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha..sup.9 described
below or a mono- or dicyclic, 5- to 10-membered hetero aryl group
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom which
may have from 1 to 3 substituents .alpha..sup.9 described
below,
[0223] here, the substituent .alpha..sup.9 represents a group
selected from the group consisting of (i) hydroxyl groups, (ii)
straight or branched chain alkoxy groups having from 1 to 4 carbon
atoms, (iii) straight or branched chain halogenated alkoxy groups
having from 1 to 4 carbon atoms, (iv) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (v) phenyl groups
which may have from 1 to 3 substituents .beta..sup.5 described
below, (vi) phenoxy groups which may have from 1 to 3 substituents
.beta..sup.5 described below, (vii) pyridyl groups which may have
from 1 to 3 substituents .beta..sup.5 described below and (viii)
mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups
containing from 1 to 4 hetero atoms selected from the group
consisting of an oxygen atom, nitrogen atom and sulfur atom,
[0224] here, the substituent .beta..sup.5 represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) hydroxyl groups, (iv) straight or branched
chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight
or branched chain hydroxyalkyl groups having from 1 to 4 carbon
atoms, (vi) halogen atoms, (vii) nitro groups, (viii) formyl
groups, (ix) carboxyl groups, (x) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms and (xi)
dialkylaminoalkyl groups in which the dialkylamino moiety has two
straight or branched chain alkyl groups having from 1 to 4 carbon
atoms which may be the same or different and the alkyl moiety is a
straight or branched chain alkyl group having from 1 to 4 carbon
atoms; and
[0225] Y is an oxygen atom, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof;
[0226] (50) amidocarboxylic acid derivatives in which
[0227] R.sup.1 is a hydrogen atom;
[0228] R.sup.2 is an ethylene group;
[0229] R.sup.3 is a hydrogen atom;
[0230] R.sup.4 is a hydrogen atom;
[0231] Z is a methylene group;
[0232] W is a phenoxy group which may have one substituent
.alpha..sup.5 described below on the phenyl moiety,
[0233] here, the substituent .alpha..sup.5represents a group
selected from the group consisting of (i) straight or branched
chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight
or branched chain halogenated alkyl groups having from 1 to 4
carbon atoms, (iii) straight or branched chain alkoxy groups having
from 1 to 4 carbon atoms, (iv) straight or branched chain
halogenated alkoxy groups having from 1 to 4 carbon atoms, (v)
straight or branched chain alkylthio groups having one or two
carbon atoms, (vi) straight or branched chain alkylsulfonyl groups
having one or two carbon atoms, (vii) halogen atoms, (viii) cyano
groups and (ix) pyridyl groups;
[0234] X represents a phenyl group which may have one substituent
.alpha..sup.12 described below,
[0235] here, the substituent .alpha..sup.12 represents a group
selected from the group consisting of methyl, isopropyl and
hydroxyl groups, fluorine atoms, chlorine atoms, diethylamino and
benzyl groups, phenyl groups (the phenyl moiety may be substituted
with 1 to 3 substituents, which may be the same or different,
including methyl, ethyl, trifluoromethyl, hydroxyl, methoxy,
ethoxy, isopropoxy, trifluoromethoxy, methylenedioxy and
hydroxymethyl groups, fluorine atoms, chlorine atoms and nitro,
formyl, cyano, carboxyl, dimethylamino, diethylamino and
N,N-dimethylaminomethyl groups), phenoxy, phenylthio,
phenylsulfonyl, phenylsulfonylamino and N-methylphenylsulfonylamino
groups, pyridyl groups (the pyridyl moiety may be substituted with
a methyl, ethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy or
trifluoromethoxy group, a fluorine atom, a chlorine atom or a
nitro, dimethylamino or diethylamino group), pyridyloxy,
pyridylthio, pyridylsulfonyl and piperidyl groups, or
[0236] X represents a pyridyl group which may have one substituent
.alpha..sup.13 described below,
[0237] here, the substituent .alpha..sup.13 represents a group
selected from the group consisting of methyl, isopropyl, methoxy,
ethoxy, isopropoxy, 2,2,3,3-tetrafluoropropoxy and benzyloxy
groups, alkylthio groups having one or two carbon atoms,
alkylsulfonyl groups having one or two carbon atoms, benzyl groups,
phenyl groups (the phenyl moiety may be substituted with a methyl,
ethyl, trifluoromethyl, methoxy, ethoxy or isopropoxy group, a
fluorine atom, a chlorine atom, or a nitro, dimethylamino or
diethylamino group), phenoxy, phenylthio, phenylsulfonyl,
phenylsulfonylamino and N-methylphenylsulfonylamino groups; and
[0238] Y is an oxygen atom, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof; and
[0239] (51) amidocarboxylic acid derivatives in which
[0240] R.sup.1 is a hydrogen atom;
[0241] R.sup.2 is an ethylene group;
[0242] R.sup.3 is a hydrogen atom;
[0243] R.sup.4 is a hydrogen atom;
[0244] Z is a methylene group;
[0245] W is a phenoxy group which may have one substituent
.alpha..sup.6 described below on the phenyl moiety,
[0246] here, the substituent .alpha..sup.6 represents a group
selected from the group consisting of methyl, ethyl, isopropyl,
t-butyl, trifluoromethyl, methoxy and trifluoromethoxy groups, and
fluorine atoms and chlorine atoms;
[0247] X is a biphenylyl group (substituents of each phenyl moiety
may be the same or different and one of them may be substituted
with a methyl, trifluoromethyl, hydroxyl, methoxy or hydroxymethyl
group, a fluorine atom, a chlorine atom, or a formyl, carboxyl,
nitro, dimethylamino or N,N-dimethylaminomethyl group), a
pyridylphenyl group (the pyridyl moiety may be substituted with one
substituent chosen from methyl, ethyl, trifluoromethyl, methoxy,
ethoxy, isopropoxy and trifluoromethoxy groups, fluorine atoms,
chlorine atoms, and nitro, dimethylamino and diethylamino groups)
or a phenylpyridyl group (the phenyl moiety may be substituted with
one substituent chosen from methyl, ethyl, trifluoromethyl,
methoxy, ethoxy and isopropoxy groups, fluorine atoms, chlorine
atoms, and nitro and dimethylamino groups); and
[0248] Y is an oxygen atom, pharmacologically acceptable salts
thereof or pharmacologically acceptable esters thereof.
[0249] Further, a compound having the following combination is
preferable.
[0250] (52) amidocarboxylic acid derivatives in which
[0251] R.sup.1 is a hydrogen atom or a straight or branched chain
alkyl group having from 1 to 6 carbon atoms;
[0252] R.sup.2 is a straight or branched chain alkylene group
having from 1 to 6 carbon atoms;
[0253] R.sup.3 is (i) a hydrogen atom, (ii) a straight or branched
chain alkyl group having from 1 to 6 carbon atoms, (iii) a straight
or branched chain alkoxy group having from 1 to 4 carbon atoms,
(iv) a straight or branched chain alkylthio group having from 1 to
4 carbon atoms, (v) a halogen atom, (vi) a nitro group, (vii) a
straight or branched chain dialkylamino group in which each alkyl
group may be the same or different and have from 1 to 4 carbon
atoms, (viii) an aryl group having from 6 to 10 carbon atoms which
may have from 1 to 3 substituents .alpha. described later or (ix)
an aralkyl group having from 7 to 12 carbon atoms which may have
from 1 to 3 substituents .alpha. described later on the aryl
moiety;
[0254] R.sup.4 is a hydrogen atom or a straight or branched chain
alkyl group having from 1 to 6 carbon atoms;
[0255] Z is a straight or branched chain alkylene group having from
1 to 4 carbon atoms;
[0256] W is an ethyl, propyl, butyl, pentyl, methoxy, ethoxy,
propoxy, isopropoxy, methylthio, ethylthio, propylthio,
isopropylthio, phenoxy, 4-methylphenoxy, 4-ethylphenoxy,
4-isopropylphenoxy, 4-methoxyphenoxy, 4-chlorophenoxy, phenylthio,
benzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl group;
[0257] X represents an aryl group having from 6 to 10 carbon atoms
which may have from 1 to 3 substituents .alpha. described later or
a mono- or dicyclic, 5- to 10-membered hetero aryl group containing
from 1 to 4 hetero atoms selected from the group consisting of an
oxygen atom, nitrogen atom and sulfur atom which may have from 1 to
3 substituents .alpha. described below,
[0258] here, the substituent .alpha. represents a group selected
from the group consisting of (i) straight or branched chain alkyl
groups having from 1 to 6 carbon atoms, (ii) straight or branched
chain halogenated alkyl groups having from 1 to 4 carbon atoms,
(iii) hydroxyl groups, (iv) straight or branched chain aliphatic
acyloxy groups having from 1 to 5 carbon atoms, (v) straight or
branched chain alkoxy groups having from 1 to 4 carbon atoms, (vi)
straight or branched chain alkylenedioxy groups having from 1 to 4
carbon atoms, (vii) aralkyloxy groups having from 7 to 12 carbon
atoms, (viii) straight or branched chain alkylthio groups having
from 1 to 4 carbon atoms, (ix) straight or branched chain
alkylsulfonyl groups having from 1 to 4 carbon atoms, (x) halogen
atoms, (xi) nitro groups, (xii) straight or branched chain
dialkylamino groups in which each alkyl group may be the same or
different and have from 1 to 4 carbon atoms, (xiii) aralkyl groups
having from 7 to 12 carbon atoms, (xiv) aryl groups having from 6
to 10 carbon atoms (the aryl moiety may be substituted with a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms, a straight or branched chain halogenated alkyl group having
from 1 to 4 carbon atoms, a straight or branched chain alkoxy group
having from 1 to 4 carbon atoms, a halogen atom or a straight or
branched chain alkylenedioxy group having from 1 to 4 carbon
atoms), (xv) aryloxy groups having from 6 to 10 carbon atoms (the
aryl moiety may be substituted with a straight or branched chain
alkyl group having from 1 to 6 carbon atoms, a straight or branched
chain halogenated alkyl group having from 1 to 4 carbon atoms, a
straight or branched chain alkoxy group having from 1 to 4 carbon
atoms, a halogen atom or a straight or branched chain alkylenedioxy
group having from 1 to 4 carbon atoms), (xvi) arylthio groups
having from 6 to 10 carbon atoms (the aryl moiety may be
substituted with a straight or branched chain alkyl having from 1
to 6 carbon atoms, a straight or branched chain halogenated alkyl
group having from 1 to 4 carbon atoms, a straight or branched chain
alkoxy group having from 1 to 4 carbon atoms, a halogen atom or a
straight or branched chain alkylenedioxy group having from 1 to 4
carbon atoms), (xvii) arylsulfonyl groups having from 6 to 10
carbon atoms (the aryl moiety may be substituted with a straight or
branched chain alkyl group having from 1 to 6 carbon atoms, a
straight or branched chain halogenated alkyl group having from 1 to
4 carbon atoms, a straight or branched chain alkoxy group having
from 1 to 4 carbon atoms, a halogen atom or a straight or branched
chain alkylenedioxy group having from 1 to 4 carbon atoms), (xviii)
arylsulfonylamino groups having from 6 to 10 carbon atoms (the aryl
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms, a straight or branched chain
halogenated alkyl group having from 1 to 4 carbon atoms, a straight
or branched chain alkoxy group having from 1 to 4 carbon atoms, a
halogen atom or a straight or branched chain alkylenedioxy group
having from 1 to 4 carbon atoms and the nitrogen atom of the amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms), (xix) mono- or dicyclic, 5-
to 10-membered hetero aryl groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom, (xx) mono- or dicyclic, 5- to
10-membered hetero aryloxy groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom, (xxi) mono- or dicyclic, 5- to
10-membered hetero arylthio groups containing from 1 to 4 hetero
atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom, (xxii) mono- or dicyclic, 5- to
10-membered hetero arylsulfonyl groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom and (xxiii) mono- or dicyclic, 5- to
10-membered hetero arylsulfonylamino groups containing from 1 to 4
hetero atoms selected from the group consisting of an oxygen atom,
nitrogen atom and sulfur atom (the nitrogen atom of the amino
moiety may be substituted with a straight or branched chain alkyl
group having from 1 to 6 carbon atoms); and
[0259] Y is a single bond, an oxygen atom, a sulfur atom or a group
of the formula: >N--R.sup.5 (wherein R.sup.5 represents a
hydrogen atom, a straight or branched chain alkyl group having from
1 to 6 carbon atoms, a straight or branched chain aliphatic acyl
group having from 1 to 8 carbon atoms or an aromatic acyl group
having from 7 to 11 carbon atoms), pharmacologically acceptable
salts thereof or pharmacologically acceptable esters thereof.
[0260] Exemplified compounds of the amidocarboxylic acid of formula
(I), pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof of the present
invention are illustrated in the following Tables.
[0261] Incidentally, the following abbreviation is used in Table 1
to Table 155.
[0262] Ex.No.Comp: Exemplification Number Compound
[0263] Ac: acetyl, Bu: butyl, tBu: t-butyl, Bimid: benzimidazolyl,
Boxa: benzoxazolyl, Bthiz: benzothiazolyl, Bz: benzyl, Dea:
diethylamino, Dma: dimethylamino, Dmam: dimethylaminomethyl, Et:
ethyl, Fur: furyl, Hex: hexyl, Imid: imidazolyl, Ind: indolyl,
Isox: isoxazolyl, MdO: methylenedioxy, Me: methyl, Mor: morpholino,
Np: naphthyl, Oxa: oxazolyl, Pen: pentyl, Ph: phenyl, Pip:
piperidinyl, PPr: 3-phenylpropyl, Pr: propyl, iPr: isopropyl, Pym:
pyrimidinyl, Pyr: pyridyl, Pyrd: pyrrolidinyl, Pyrr: pyrrolyl,
Pyza: pyrazolyl, Quin: quinolyl, iQuin: isoquinolyl, Tfp:
2,2,3,3-tetrafluoropropyl, Thi: thienyl, Thiz: thiazolyl.
[0264] It should be noted that the compounds of Table 1 to Table
145 have the following formula (Ia) and the compounds of Table 146
to Table 155 have the following formula (Ib).
1TABLE 1 (Ia) 3 (Ib) 4 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3
R.sup.4 Z W X Y 1-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO Ph O 1-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Np O 1-3 H (CH.sub.2).sub.2 H H
CH.sub.2 EtO 2-Np O 1-4 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Me-Ph
O 1-5 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Et-Ph O 1-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-iPr-Ph O 1-7 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 4-iPr-Ph O 1-8 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
3-tBu-Ph O 1-9 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-tBu-Ph O 1-10
H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-F-Ph O 1-11 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-F-Ph O 1-12 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 4-Cl-Ph O 1-13 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-Br-Ph O 1-14 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph--Ph O 1-15
H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph O 1-16 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-BzO-Ph O 1-17 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Bz-Ph O 1-18 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 3-PhO-Ph O 1-19 H (CH.sub.2).sub.2 H H CH.sub.2
EtO 4-PhO-Ph O 1-20 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-PhS-Ph O
1-21 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-PhS-Ph O 1-22 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-PhSO.sub.2-Ph O 1-23 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-PhSO.sub.2-Ph O 1-24 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Imid-1)-Ph O 1-25 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Imid-1)-Ph O 1-26 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Imid-4)-Ph O 1-27 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Imid-4)-Ph O 1-28 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Fur-2)-Ph O 1-29 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Fur-2)-Ph O 1-30 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Thi-2)-Ph O 1-31 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Thi-2)-Ph O 1-32 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Thi-3)-Ph O 1-33 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Thi-3)-Ph O 1-34 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Pyr-2)-Ph O 1-35 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph O 1-36 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Pyr-3)-Ph O 1-37 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph O 1-38 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Pyr-4)-Ph O 1-39 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph O 1-40 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Oxa-2)-Ph O 1-41 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Oxa-2)-Ph O 1-42 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Oxa-4)-Ph O 1-43 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Oxa-4)-Ph O 1-44 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Oxa-5)-Ph O 1-45 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Oxa-5)-Ph O 1-46 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Thiz-2)-Ph O 1-47 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Thiz-2)-Ph O 1-48 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Thiz-4)-Ph O 1-49 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Thiz-4)-Ph O 1-50 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(Thiz-5)-Ph O 1-51 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Thiz-5)-Ph O 1-52 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-2-Pyrr O 1-53 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Ph-2-Pyrr O 1-54 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Bz-2-Pyrr O 1-55 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Me-2-Fur O 1-56 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Ph-2-Fur O 1-57 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Me-2-Thi O 1-58 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Ph-2-Thi O 1-59 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Me-3-Thi O 1-60 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Ph-3-Thi O 1-61 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-3-Pyza O 1-62 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Ph-3-Pyza O 1-63 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-2-Imid O 1-64 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Ph-2-Imid O 1-65 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-4-Imid O 1-66 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Ph-4-Imid O 1-67 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Oxa O 1-68 H (CH.sub.2).sub.2 H
H CH.sub.2 EtO 5-Oxa O 1-69 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-Me-4-Oxa O 1-70 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-4-Oxa O
1-71 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Oxa O 1-72 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Oxa O 1-73 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Me-2-Ph-5-Oxa O 1-74 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Me-2-Ph-4-Oxa O 1-75 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Thiz O 1-76 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 5-Thiz O 1-77 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-Me-4-Thiz O 1-78 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-4-Thiz
O 1-79 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Thiz O 1-80 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Thiz O 1-81 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Me-2-Ph-5-Thiz O 1-82 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 5-Me-2-Ph-4-Thiz O 1-83 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-4-Pyza O 1-84 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Ph-4-Pyza O 1-85 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-4-Isox O 1-86 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-4-Isox O 1-87 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Pyr O 1-88 H (CH.sub.2).sub.2 H
H CH.sub.2 EtO 3-Pyr O 1-89 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-Pyr O 1-90 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Me-5-Pyr O 1-91
H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Et-5-Pyr O 1-92 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-5-Pyr O 1-93 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Pyr O 1-94 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-BzO-5-Pyr O 1-95 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr O 1-96 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeO-5-Pyr O 1-97 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtO-5-Pyr O 1-98 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrO-5-Pyr O 1-99 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeS-5-Pyr O 1-100 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtS-5-Pyr O 1-101 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhSO.sub.2NH-5-Pyr O 1-102 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeSO.sub.2-5-Pyr O 1-103 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtSO.sub.2-5-Pyr O 1-104 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhSO.sub.2NMe-5-Pyr O 1-105 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Bz-5-Pyr O 1-106 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhO-5-Pyr O 1-107 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhS-5-Pyr O 1-108 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhSO.sub.2-5-Pyr O 1-109 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Me-6-Pyr O 1-110 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr O 1-111 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-6-Pyr O 1-112 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-6-Pyr O 1-113 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-4-Pym O 1-114 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-4-Pym O 1-115 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeO-4-Pym O 1-116 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtO-4-Pym O 1-117 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrO-4-Pym O 1-118 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeS-4-Pym O 1-119 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtS-4-Pym O 1-120 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrS-4-Pym O 1-121 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 6-MeS-4-Pym O 1-122 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 6-EtS-4-Pym O 1-123 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 6-iPrS-4-Pym O 1-124 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhS-4-Pym O 1-125 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeSO.sub.2-4-Pym O 1-126 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtSO.sub.2-4-Pym O 1-127 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrSO.sub.2-4-Pym O 1-128 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhSO.sub.2-4-Pym O 1-129 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Pym O 1-130 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pym O 1-131 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeO-5-Pym O 1-132 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtO-5-Pym O 1-133 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrO-5-Pym O 1-134 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeS-5-Pym O 1-135 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtS-5-Pym O 1-136 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrS-5-Pym O 1-137 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhS-5-Pym O 1-138 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeSO.sub.2-5-Pym O 1-139 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtSO.sub.2-5-Pym O 1-140 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrSO.sub.2-5-Pym O 1-141 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-PhSO.sub.2-5-Pym O 1-142 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ind O 1-143 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 3-Ind O 1-144 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
1-Me-2-Ind O 1-145 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-3-Ind O
1-146 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Bimid O 1-147 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Boxa O 1-148 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 2-Bthiz O 1-149 H (CH.sub.2).sub.2 H H CH.sub.2
EtO 2-Quin O 1-150 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Quin O
1-151 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Quin O 1-152 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-iQuin O 1-153 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-iQuin O 1-154 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-iQuin O 1-155 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-MeO-Ph O 1-156 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-MeO-Ph O 1-157 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-EtO-Ph O 1-158 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-EtO-Ph O 1-159 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-iPrO-Ph O 1-160 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-iPrO-Ph O 1-161 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-MeS-Ph O 1-162 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-MeS-Ph O 1-163 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-EtS-Ph O 1-164 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-EtS-Ph O 1-165 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-iPrS-Ph O 1-166 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-iPrS-Ph O 1-167 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-MeSO.sub.2-Ph O 1-168 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-MeSO.sub.2-Ph O 1-169 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-EtSO.sub.2-Ph O 1-170 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-EtSO.sub.2-Ph O 1-171 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-iPrSO.sub.2-Ph O 1-172 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-iPrSO.sub.2-Ph O 1-173 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-(1-Me-Imid-4)-Ph O 1-174 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(1-Me-Imid-4)-Ph O 1-175 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1-Me-2-Ph-4-Imid O 1-176 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1,4-di-Me-2-Ph-5- O Imid 1-177 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 1,5-di-Me-2-Ph-4- O Imid 1-178 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3,4-MdO-Ph O 1-179 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-MeO-Ph)--Ph O 1-180 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3,4-MdO- O Ph)--Ph 1-181 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[PhSO.sub.2N(Me)]-Ph O 1-182 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[(Pyr-3)SO.sub.2N O (Me)]-Ph
1-183 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(PhSO.sub.2NH)-Ph O
1-184 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[(Pyr-3)SO.sub.2NH]- O
Ph 1-185 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[(Pyr-2)SO.sub.2]-Ph
O 1-186 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[(Pyr-3)SO.sub.2]-Ph
O 1-187 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-[(Pyr-2)SO.sub.2N O
(Me)]-Ph 1-188 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-[(Pyr-2)SO.sub.2NH]- O Ph 1-189 H (CH.sub.2).sub.2 H H CH.sub.2
EtO 4-(4-Me-Ph)--Ph O 1-190 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-(4-F-Ph)--Ph O 1-191 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-(4-CF.sub.3-Ph)--Ph O 1-192 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-[PhSO.sub.2N(Me)]-5- O Pyr 1-193 H (CH.sub.2).sub.2 H H CH.sub.2
EtO 2-HO-5-Pyr O 1-194 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-BzO-5-Pyr O 1-195 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-[(Pyr-4)SO.sub.2]-Ph O 1-196 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-[(Pyr-4)O]-Ph O 1-197 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-[(Pyr-4)S]-Ph O 1-198 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 3-HO-Ph
O 1-199 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-HO-Ph O 1-200 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-HO-3,4,6-tri-Me- O Ph 1-201 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-HO-3,5-di-Me-Ph O 1-202 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-AcO-Ph O 1-203 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-AcO-Ph O 1-204 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-Cl-Ph)--Ph O 1-205 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-HO-3,5-di-Me- O Ph)--Ph
1-206 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-HO-Ph)--Ph O 1-207 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-OHC-Ph)--Ph O 1-208 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-Dmam- O Ph)--Ph 1-209 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-Dma-Ph)--Ph O 1-210 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-HOOC- O Ph)--Ph 1-211 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-HOH.sub.2C- O Ph)--Ph 1-212
H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-MeO-Ph)--Ph O 1-213 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-HO-Ph)--Ph O 1-214 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-OHC-Ph)--Ph O 1-215 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Dmam- O Ph)--Ph 1-216 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Dma-Ph)-Ph O 1-217 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-HOOC- O Ph)--Ph 1-218 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-HOH.sub.2C- O Ph)--Ph 1-219
H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(2-MeO-Ph)--Ph O 1-220 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(2-HO-Ph)--Ph O 1-221 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(2-OHC-Ph)--Ph O 1-222 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 1-223 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-EtO-Pyr-6)-Ph O 1-224 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-iPrO-Pyr-6)- O Ph 1-225 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 1-226 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Dea-Pyr-6)-Ph O 1-227 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-F.sub.3C-Pyr-6)-Ph O 1-228 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-O.sub.2N-Pyr-6)-Ph O 1-229 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Pip-Ph O 1-230 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Dea-Ph O 1-231 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-F-Ph)-5-Pyr O 1-232 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-Cl-Ph)-5-Pyr O 1-233 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-MeO-Ph)-5-Pyr O 1-234 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-EtO-Ph)-5-Pyr O 1-235 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-iPrO-Ph)-5- O Pyr 1-236 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-TfpO-5-Pyr O 1-237 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(4-AcO-Ph)--Ph O 1-238 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-F-Ph)--Ph O 1-239 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Cl-Ph)--Ph O 1-240 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Me-Ph)--Ph O 1-241 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-AcO-Ph)--Ph O 1-242 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Me-Pyr-6)-Ph O 1-243 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(3-Et-Pyr-6)-Ph O 1-244 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-Me-Ph)-5-Pyr O 1-245 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-CF.sub.3-Ph)-5-Pyr O 1-246 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(4-Dma-Ph)-5-Pyr O 1-247 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(3-F-Ph)-5-Pyr O 1-248 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-(3-Cl-Ph)-5-Pyr O 1-249 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-MeO-Ph)-5-Pyr O 1-250 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-EtO-Ph)-5-Pyr O 1-251 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-iPrO-Ph)-5-Pyr O 1-252 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-Me-Ph)-5-Pyr O 1-253 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-CF.sub.3-Ph)-5-Pyr O 1-254 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
2-(3-Dma-Ph)-5-Pyr O
[0265]
2TABLE 2 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 2-1
H (CH.sub.2).sub.2 H H CH.sub.2 MeO Ph O 2-2 H (CH.sub.2).sub.2 H H
CH.sub.2 MeO 1-Np O 2-3 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Np O
2-4 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Me--Ph O 2-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Et--Ph O 2-6 H (CH.sub.2).sub.2
H H CH.sub.2 MeO 3-iPr--Ph O 2-7 H (CH.sub.2).sub.2 H H CH.sub.2
MeO 4-iPr--Ph O 2-8 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-tBu--Ph O
2-9 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-tBu--Ph O 2-10 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-F--Ph O 2-11 H (CH.sub.2).sub.2
H H CH.sub.2 MeO 4-F--Ph O 2-12 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-Cl--Ph O 2-13 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Br--Ph O 2-14
H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Ph--Ph O 2-15 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Ph--Ph O 2-16 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-BzO--Ph O 2-17 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Bz-Ph O 2-18 H (CH.sub.2).sub.2
H H CH.sub.2 MeO 3-PhO--Ph O 2-19 H (CH.sub.2).sub.2 H H CH.sub.2
MeO 4-PhO--Ph O 2-20 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-PhS--Ph
O 2-21 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-PhS--Ph O 2-22 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-PhSO.sub.2--Ph O 2-23 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-PhSO.sub.2--Ph O 2-24 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Imid-1)-Ph O 2-25 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Imid-1)-Ph O 2-26 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Imid-4)-Ph O 2-27 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Imid-4)-Ph O 2-28 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Fur-2)-Ph O 2-29 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Fur-2)-Ph O 2-30 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Thi-2)-Ph O 2-31 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Thi-2)-Ph O 2-32 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Thi-3)-Ph O 2-33 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Thi-3)-Ph O 2-34 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Pyr-2)-Ph O 2-35 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Pyr-2)-Ph O 2-36 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Pyr-3)-Ph O 2-37 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Pyr-3)-Ph O 2-38 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Pyr-4)-Ph O 2-39 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Pyr-4)-Ph O 2-40 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Oxa-2)-Ph O 2-41 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Oxa-2)-Ph O 2-42 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Oxa-4)-Ph O 2-43 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Oxa-4)-Ph O 2-44 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Oxa-5)-Ph O 2-45 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Oxa-5)-Ph O 2-46 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Thiz-2)-Ph O 2-47 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Thiz-2)-Ph O 2-48 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Thiz-4)-Ph O 2-49 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Thiz-4)-Ph O 2-50 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(Thiz-5)-Ph O 2-51 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(Thiz-5)-Ph O 2-52 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-2-Pyrr O 2-53 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Ph-2-Pyrr O 2-54 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Bz-2-Pyrr O 2-55 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Me-2-Fur O 2-56 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Ph-2-Fur O 2-57 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Me-2-Thi O 2-58 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Ph-2-Thi O 2-59 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Me-3-Thi O 2-60 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Ph-3-Thi O 2-61 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-3-Pyza O 2-62 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Ph-3-Pyza O 2-63 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-2-Imid O 2-64 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Ph-2-Imid O 2-65 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-4-Imid O 2-66 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Ph-4-Imid O 2-67 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Oxa O 2-68 H (CH.sub.2).sub.2 H
H CH.sub.2 MeO 5-Oxa O 2-69 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-Me-4-Oxa O 2-70 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-4-Oxa O
2-71 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-5-Oxa O 2-72 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-5-Oxa O 2-73 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Me-2-Ph-5-Oxa O 2-74 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Me-2-Ph-4-Oxa O 2-75 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Thiz O 2-76 H (CH.sub.2).sub.2
H H CH.sub.2 MeO 5-Thiz O 2-77 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-Me-4-Thiz O 2-78 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-4-Thiz
O 2-79 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-5-Thiz O 2-80 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-5-Thiz O 2-81 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Me-2-Ph-5-Thiz O 2-82 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 5-Me-2-Ph-4-Thiz O 2-83 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-4-Pyza O 2-84 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Ph-4-Pyza O 2-85 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-4-Isox O 2-86 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-4-Isox O 2-87 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Pyr O 2-88 H (CH.sub.2).sub.2 H
H CH.sub.2 MeO 3-Pyr O 2-89 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-Pyr O 2-90 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Me-5-Pyr O 2-91
H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Et-5-Pyr O 2-92 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Ph-5-Pyr O 2-93 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-5-Pyr O 2-94 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-BzO-5-Pyr O 2-95 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-5-Pyr O 2-96 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeO-5-Pyr O 2-97 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtO-5-Pyr O 2-98 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-iPrO-5-Pyr O 2-99 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeS-5-Pyr O 2-100 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtS-5-Pyr O 2-101 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhSO.sub.2NH-5-Pyr O 2-102 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeSO.sub.2-5-Pyr O 2-103 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtSO.sub.2-5-Pyr O 2-104 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhSO.sub.2NMe-5-Pyr O 2-105 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Bz-5-Pyr O 2-106 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhO-5-Pyr O 2-107 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhS-5-Pyr O 2-108 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhSO.sub.2-5-Pyr O 2-109 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Me-6-Pyr O 2-110 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Ph-6-Pyr O 2-111 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-6-Pyr O 2-112 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-6-Pyr O 2-113 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-4-Pym O 2-114 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-4-Pym O 2-115 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeO-4-Pym O 2-116 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtO-4-Pym O 2-117 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-iPrO-4-Pym O 2-118 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeS-4-Pym O 2-119 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtS-4-Pym O 2-120 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-iPrS-4-Pym O 2-121 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 6-MeS-4-Pym O 2-122 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 6-EtS-4-Pym O 2-123 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 6-iPrS-4-Pym O 2-124 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhS-4-Pym O 2-125 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeSO.sub.2-4-Pym O 2-126 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtSO.sub.2-4-Pym O 2-127 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-iPrSO.sub.2-4-Pym O 2-128 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-PhSO.sub.2-4-Pym O 2-129 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Me-5-Pym O 2-130 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Ph-5-Pym O 2-131 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeO-5-Pym O 2-132 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-EtO-5-Pym O 2-133 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-iPrO-5-Pym O 2-134 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-MeS-5-Pym O 2-135 H (CH.sub.2)2
H H CH.sub.2 MeO 2-EtS-5-Pym O 2-136 H (CH.sub.2)2 H H CH.sub.2 MeO
2-iPrS-5-Pym O 2-137 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-PhS-5-Pym O 2-138 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-MeSO.sub.2-5-Pym O 2-139 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-EtSO.sub.2-5-Pym O 2-140 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-iPrSO.sub.2-5-Pym O 2-141 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-PhSO.sub.2-5-Pym O 2-142 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
2-Ind O 2-143 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Ind O 2-144 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-2-Ind O 2-145 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-3-lnd O 2-146 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Bimid O 2-147 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 2-Boxa O 2-148 H (CH.sub.2).sub.2
H H CH.sub.2 MeO 2-Bthiz O 2-149 H (CH.sub.2).sub.2 H H CH.sub.2
MeO 2-Quin O 2-150 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-Quin O
2-151 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-Quin O 2-152 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-iQuin O 2-153 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-iQuin O 2-154 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-iQuin O 2-155 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-MeO--Ph O 2-156 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-MeO--Ph O 2-157 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-EtO--Ph O 2-158 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-EtO--Ph O 2-159 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-iPrO--Ph O 2-160 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-iPrO--Ph O 2-161 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-MeS--Ph O 2-162 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-MeS--Ph O 2-163 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-EtS--Ph O 2-164 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-EtS--Ph O 2-165 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-iPrS--Ph O 2-166 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-iPrS--Ph O 2-167 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-MeSO.sub.2--Ph O 2-168 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-MeSO.sub.2--Ph O 2-169 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-EtSO.sub.2--Ph O 2-170 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-EtSO.sub.2--Ph O 2-171 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-iPrSO.sub.2--Ph O 2-172 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-iPrSO.sub.2--Ph O 2-173 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3-(1-Me-Imid-4)-Ph O 2-174 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(1-Me-Imid-4)-Ph O 2-175 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1-Me-2-Ph-4-Imid O 2-176 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1,4-di-Me-2-Ph-5-Imid O 2-177 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 1,5-di-Me-2-Ph-4-Imid O 2-178 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 3,4-MdO--Ph O 2-179 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(4-MeO--Ph)--Ph O 2-180 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(3,4-MdO--Ph)--Ph O 2-181 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-[PhSO.sub.2N(Me)]--Ph O 2-182 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-[(Pyr-3)SO.sub.2N(Me)]--Ph O
2-183 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-(PhSO.sub.2NH)-Ph O
2-184 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-[(Pyr-3)SO.sub.2NH]--Ph
O 2-185 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-[(Pyr-2)SO.sub.2]--Ph
O 2-186 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-[(Pyr-3)SO.sub.2]--Ph
O 2-187 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-[(Pyr-2)SO.sub.2N(Me)]--- Ph O 2-188 H (CH.sub.2).sub.2 H H
CH.sub.2 MeO 4-[(Pyr-2)SO.sub.2NH]--Ph O 2-189 H (CH.sub.2).sub.2 H
H CH.sub.2 MeO 4-(4-Me--Ph)--Ph O 2-190 H (CH.sub.2).sub.2 H H
CH.sub.2 MeO 4-(4-F--Ph)--Ph O 2-191 H (CH.sub.2).sub.2 H H
CH.sub.2 MeO 4-(4-CF.sub.3--Ph)--Ph O 2-192 H (CH.sub.2).sub.2 H H
CH.sub.2 MeO 2-[PhSO.sub.2N(Me)]-5-Pyr O 2-193 H (CH.sub.2).sub.2 H
H CH.sub.2 MeO 2-HO-5-Pyr O 2-194 H (CH.sub.2).sub.2 H H CH.sub.2
MeO 2-BzO-5-Pyr O 2-195 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-[(Pyr-4)SO.sub.2]--Ph O 2-196 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-[(Pyr-4)O]--Ph O 2-197 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
4-[(Pyr-4)S]--Ph O 2-198 H (CH.sub.2).sub.2 H H CH.sub.2 MeO
3-HO--Ph O 2-199 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-HO--Ph O
2-200 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 2-HO-3,4,6-tri-Me--Ph O
2-201 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 4-HO-3,5-di-Me--Ph O
2-202 H (CH.sub.2).sub.2 H H CH.sub.2 MeO 3-AcO--Ph O 2-203 H
(CH.sub.2).sub.2 H H CH.sub.2 MeO 4-AcO--Ph O
[0266]
3TABLE 3 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 3-1
H (CH.sub.2).sub.2 H H CH.sub.2 Pr Ph O 3-2 H (CH.sub.2).sub.2 H H
CH.sub.2 Pr 1-Np O 3-3 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Np O
3-4 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Me--Ph O 3-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Et--Ph O 3-6 H (CH.sub.2).sub.2
H H CH.sub.2 Pr 3-iPr--Ph O 3-7 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-iPr--Ph O 3-8 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-tBu--Ph O 3-9
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-tBu--Ph O 3-10 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-F--Ph O 3-11 H (CH.sub.2).sub.2
H H CH.sub.2 Pr 4-F--Ph O 3-12 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-Cl--Ph O 3-13 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Br--Ph O 3-14
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph--Ph O 3-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph--Ph O 3-16 H (CH.sub.2).sub.2
H H CH.sub.2 Pr 4-BzO--Ph O 3-17 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-Bz-Ph O 3-18 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-PhO--Ph O 3-19
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-PhO--Ph O 3-20 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-PhS--Ph O 3-21 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-PhS--Ph O 3-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-PhSO.sub.2--Ph O 3-23 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-PhSO.sub.2--Ph O 3-24 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Imid-1)-Ph O 3-25 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Imid-1)-Ph O 3-26 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Imid-4)-Ph O 3-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Imid-4)-Ph O 3-28 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Fur-2)-Ph O 3-29 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Fur-2)-Ph O 3-30 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Thi-2)-Ph O 3-31 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Thi-2)-Ph O 3-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Thi-3)-Ph O 3-33 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Thi-3)-Ph O 3-34 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Pyr-2)-Ph O 3-35 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph O 3-36 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Pyr-3)-Ph O 3-37 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph O 3-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Pyr-4)-Ph O 3-39 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph O 3-40 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Oxa-2)-Ph O 3-41 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Oxa-2)-Ph O 3-42 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Oxa-4)-Ph O 3-43 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Oxa-4)-Ph O 3-44 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Oxa-5)-Ph O 3-45 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Oxa-5)-Ph O 3-46 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Thiz-2)-Ph O 3-47 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Thiz-2)-Ph O 3-48 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Thiz-4)-Ph O 3-49 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Thiz-4)-Ph O 3-50 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(Thiz-5)-Ph O 3-51 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Thiz-5)-Ph O 3-52 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-2-Pyrr O 3-53 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Ph-2-Pyrr O 3-54 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Bz-2-Pyrr O 3-55 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Me-2-Fur O 3-56 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Ph-2-Fur O 3-57 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Me-2-Thi O 3-58 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Ph-2-Thi O 3-59 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Me-3-Thi O 3-60 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Ph-3-Thi O 3-61 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-3-Pyza O 3-62 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Ph-3-Pyza O 3-63 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-2-Imid O 3-64 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Ph-2-Imid O 3-65 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-4-Imid O 3-66 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Ph-4-Imid O 3-67 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Oxa O 3-68 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 5-Oxa O 3-69 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
2-Me-4-Oxa O 3-70 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-4-Oxa O
3-71 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Oxa O 3-72 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Oxa O 3-73 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Me-2-Ph-5-Oxa O 3-74 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Me-2-Ph-4-Oxa O 3-75 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Thiz O 3-76 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 5-Thiz O 3-77 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
2-Me-4-Thiz O 3-78 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-4-Thiz O
3-79 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Thiz O 3-80 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Thiz O 3-81 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Me-2-Ph-5-Thiz O 3-82 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 5-Me-2-Ph-4-Thiz O 3-83 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-4-Pyza O 3-84 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Ph-4-Pyza O 3-85 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-4-Isox O 3-86 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-4-Isox O 3-87 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Pyr O 3-88 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 3-Pyr O 3-89 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Pyr
O 3-90 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Me-5-Pyr O 3-91 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Et-5-Pyr O 3-92 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-5-Pyr O 3-93 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Pyr O 3-94 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-BzO-5-Pyr O 3-95 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr O 3-96 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeO-5-Pyr O 3-97 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtO-5-Pyr O 3-98 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pyr O 3-99 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeS-5-Pyr O 3-100 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtS-5-Pyr O 3-101 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhSO.sub.2NH-5-Pyr O 3-102 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeSO.sub.2-5-Pyr O 3-103 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtSO.sub.2-5-Pyr O 3-104 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhSO.sub.2NMe-5-Pyr O 3-105 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Bz-5-Pyr O 3-106 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhO-5-Pyr O 3-107 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhS-5-Pyr O 3-108 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhSO.sub.2-5-Pyr O 3-109 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Me-6-Pyr O 3-110 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr O 3-111 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-6-Pyr O 3-112 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-6-Pyr O 3-113 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-4-Pym O 3-114 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-4-Pym O 3-115 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeO-4-Pym O 3-116 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtO-4-Pym O 3-117 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrO-4-Pym O 3-118 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeS-4-Pym O 3-119 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtS-4-Pym O 3-120 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrS-4-Pym O 3-121 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 6-MeS-4-Pym O 3-122 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 6-EtS-4-Pym O 3-123 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 6-iPrS-4-Pym O 3-124 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhS-4-Pym O 3-125 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeSO.sub.2-4-Pym O 3-126 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtSO.sub.2-4-Pym O 3-127 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrSO.sub.2-4-Pym O 3-128 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhSO.sub.2-4-Pym O 3-129 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Pym O 3-130 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pym O 3-131 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeO-5-Pym O 3-132 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtO-5-Pym O 3-133 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pym O 3-134 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeS-5-Pym O 3-135 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtS-5-Pym O 3-136 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrS-5-Pym O 3-137 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhS-5-Pym O 3-138 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeSO.sub.2-5-Pym O 3-139 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtSO.sub.2-5-Pym O 3-140 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrSO.sub.2-5-Pym O 3-141 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-PhSO.sub.2-5-Pym O 3-142 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ind O 3-143 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 3-Ind O 3-144 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
1-Me-2-Ind O 3-145 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-3-Ind O
3-146 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Bimid O 3-147 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Boxa O 3-148 H (CH.sub.2).sub.2
H H CH.sub.2 Pr 2-Bthiz O 3-149 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
2-Quin O 3-150 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Quin O 3-151 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Quin O 3-152 H (CH.sub.2).sub.2
H H CH.sub.2 Pr 1-iQuin O 3-153 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
3-iQuin O 3-154 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-iQuin O 3-155
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-MeO--Ph O 3-156 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-MeO--Ph O 3-157 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-EtO--Ph O 3-158 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-EtO--Ph O 3-159 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-iPrO--Ph O 3-160 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-iPrO--Ph O 3-161 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-MeS--Ph O 3-162 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-MeS--Ph O 3-163 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-EtS--Ph O 3-164 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-EtS--Ph O 3-165 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-iPrS--Ph O 3-166 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-iPrS--Ph O 3-167 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-MeSO.sub.2--Ph O 3-168 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-MeSO.sub.2--Ph O 3-169 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-EtSO.sub.2--Ph O 3-170 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-EtSO.sub.2--Ph O 3-171 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-iPrSO.sub.2--Ph O 3-172 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-iPrSO.sub.2--Ph O 3-173 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-(1-Me-Imid-4)-Ph O 3-174 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(1-Me-Imid-4)-Ph O 3-175 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1-Me-2-Ph-4-Imid O 3-176 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1,4-di-Me-2-Ph-5-Imid O 3-177 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 1,5-di-Me-2-Ph-4-Imid O 3-178 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3,4-MdO--Ph O 3-179 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-MeO--Ph)--Ph O 3-180 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3,4-MdO--Ph)--Ph O 3-181 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-[PhSO.sub.2N(Me)]--Ph O 3-182 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-[(Pyr-3)SO.sub.2N(Me)]--Ph O
3-183 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(PhSO.sub.2NH)-Ph O
3-184 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-[(Pyr-3)SO.sub.2NH]--Ph
O 3-185 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-[(Pyr-2)SO.sub.2]--Ph
O 3-186 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-[(Pyr-3)SO.sub.2]--Ph
O 3-187 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-[(Pyr-2)SO.sub.2N(Me)]--Ph O 3-188 H (CH.sub.2).sub.2 H H
CH.sub.2 Pr 4-[(Pyr-2)SO.sub.2NH]--Ph O 3-189 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 4-(4-Me--Ph)--Ph O 3-190 H (CH.sub.2).sub.2 H H
CH.sub.2 Pr 4-(4-F--Ph)--Ph O 3-191 H (CH.sub.2).sub.2 H H CH.sub.2
Pr 4-(4-CF.sub.3--Ph)--Ph O 3-192 H (CH.sub.2).sub.2 H H CH.sub.2
Pr 2-[PhSO.sub.2N(Me)]-5-Pyr O 3-193 H (CH.sub.2).sub.2 H H
CH.sub.2 Pr 2-HO-5-Pyr O 3-194 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
2-BzO-5-Pyr O 3-195 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-[(Pyr-4)SO.sub.2]--Ph O 3-196 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-[(Pyr-4)O]--Ph O 3-197 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-[(Pyr-4)S]--Ph O 3-198 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
3-HO--Ph O 3-199 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-HO--Ph O
3-200 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-HO-3,4,6-tri-Me--Ph O
3-201 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-HO-3,5-di-Me--Ph O 3-202
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 3-AcO--Ph O 3-203 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-AcO--Ph O 3-204 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-Cl--Ph)--Ph O 3-205 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-HO-3,5-di-Me--Ph)--Ph O 3-206
H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-HO--Ph)--Ph O 3-207 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-OHC--Ph)--Ph O 3-208 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-Dmam-Ph)--Ph O 3-209 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-Dma-Ph)--Ph O 3-210 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-HOOC--Ph)--Ph O 3-211 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-HOH.sub.2C--Ph)--Ph O 3-212 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-MeO--Ph)--Ph O 3-213 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-HO--Ph)--Ph O 3-214 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-OHC--Ph)--Ph O 3-215 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Dmam-Ph)--Ph O 3-216 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Dmam-Ph)--Ph O 3-217 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-HOOC--Ph)--Ph O 3-218 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-HOH.sub.2C--Ph)--Ph O 3-219 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(2-MeO--Ph)--Ph O 3-220 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(2-HO--Ph)--Ph O 3-221 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(2-OHC--Ph)--Ph O 3-222 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 3-223 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-EtO-Pyr-6)-Ph O 3-224 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-iPrO-Pyr-6)-Ph O 3-225 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 3-226 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Dea-Pyr-6)-Ph O 3-227 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-F.sub.3C-Pyr-6)-Ph O 3-228 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-O.sub.2N-Pyr-6)-Ph O 3-229 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Pip-Ph O 3-230 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Dea-Ph O 3-231 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 3-232 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-Cl--Ph)-5-Pyr O 3-233 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 3-234 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-EtO--Ph)-5-Pyr O 3-235 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-iPrO--Ph)-5-Pyr O 3-236 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-TfpO-5-Pyr O 3-237 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(4-AcO--Ph)--Ph O 3-238 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-F--Ph)--Ph O 3-239 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Cl--Ph)--Ph O 3-240 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Me--Ph)--Ph O 3-241 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-AcO--Ph)--Ph O 3-242 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Me-Pyr-6)-Ph O 3-243 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Et-Pyr-6)-Ph O 3-244 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-Me--Ph)-5-Pyr O 3-245 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-CF.sub.3--Ph)-5-Pyr O 3-246 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(4-Dma-Ph)-5-Pyr O 3-247 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-F--Ph)-5-Pyr O 3-248 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-Cl--Ph)-5-Pyr O 3-249 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-MeO--Ph)-5-Pyr O 3-250 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-EtO--Ph)-5-Pyr O 3-251 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-iPrO--Ph)-5-Pyr O 3-252 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-Me--Ph)-5-Pyr O 3-253 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-CF.sub.3--Ph)-5-Pyr O 3-254 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-(3-Dma-Ph)-5-Pyr O
[0267]
4TABLE 4 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 4-1
H (CH.sub.2).sub.2 H H CH.sub.2 Bu Ph O 4-2 H (CH.sub.2).sub.2 H H
CH.sub.2 Bu 1-Np O 4-3 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Np O
4-4 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Me--Ph O 4-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Et--Ph O 4-6 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 3-iPr--Ph O 4-7 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-iPr--Ph O 4-8 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-tBu--Ph O 4-9
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-tBu--Ph O 4-10 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-F--Ph O 4-11 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 4-F--Ph O 4-12 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-Cl--Ph O 4-13 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Br--Ph O 4-14
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph--Ph O 4-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 4-16 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 4-BzO--Ph O 4-17 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-Bz-Ph O 4-18 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-PhO--Ph O 4-19
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-PhO--Ph O 4-20 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-PhS--Ph O 4-21 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-PhS--Ph O 4-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-PhSO.sub.2--Ph O 4-23 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-PhSO.sub.2--Ph O 4-24 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Imid-1)-Ph O 4-25 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Imid-1)-Ph O 4-26 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Imid-4)-Ph O 4-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Imid-4)-Ph O 4-28 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Fur-2)-Ph O 4-29 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Fur-2)-Ph O 4-30 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Thi-2)-Ph O 4-31 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Thi-2)-Ph O 4-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Thi-3)-Ph O 4-33 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Thi-3)-Ph O 4-34 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Pyr-2)-Ph O 4-35 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 4-36 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Pyr-3)-Ph O 4-37 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 4-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Pyr-4)-Ph O 4-39 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 4-40 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Oxa-2)-Ph O 4-41 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Oxa-2)-Ph O 4-42 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Oxa-4)-Ph O 4-43 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Oxa-4)-Ph O 4-44 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Oxa-5)-Ph O 4-45 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Oxa-5)-Ph O 4-46 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Thiz-2)-Ph O 4-47 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Thiz-2)-Ph O 4-48 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Thiz-4)-Ph O 4-49 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Thiz-4)-Ph O 4-50 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(Thiz-5)-Ph O 4-51 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Thiz-5)-Ph O 4-52 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-2-Pyrr O 4-53 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Ph-2-Pyrr O 4-54 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Bz-2-Pyrr O 4-55 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Me-2-Fur O 4-56 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Ph-2-Fur O 4-57 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Me-2-Thi O 4-58 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Ph-2-Thi O 4-59 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Me-3-Thi O 4-60 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Ph-3-Thi O 4-61 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-3-Pyza O 4-62 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Ph-3-Pyza O 4-63 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-2-Imid O 4-64 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Ph-2-Imid O 4-65 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-4-Imid O 4-66 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Ph-4-Imid O 4-67 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Oxa O 4-68 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 5-Oxa O 4-69 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
2-Me-4-Oxa O 4-70 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-4-Oxa O
4-71 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-5-Oxa O 4-72 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Oxa O 4-73 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Me-2-Ph-5-Oxa O 4-74 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Me-2-Ph-4-Oxa O 4-75 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Thiz O 4-76 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 5-Thiz O 4-77 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
2-Me-4-Thiz O 4-78 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-4-Thiz O
4-79 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-5-Thiz O 4-80 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Thiz O 4-81 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Me-2-Ph-5-Thiz O 4-82 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 5-Me-2-Ph-4-Thiz O 4-83 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-4-Pyza O 4-84 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Ph-4-Pyza O 4-85 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-4-Isox O 4-86 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-4-Isox O 4-87 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Pyr O 4-88 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 3-Pyr O 4-89 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Pyr
O 4-90 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Me-5-Pyr O 4-91 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Et-5-Pyr O 4-92 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-5-Pyr O 4-93 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-5-Pyr O 4-94 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-BzO-5-Pyr O 4-95 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr O 4-96 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeO-5-Pyr O 4-97 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtO-5-Pyr O 4-98 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pyr O 4-99 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeS-5-Pyr O 4-100 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtS-5-Pyr O 4-101 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhSO.sub.2NH-5-Pyr O 4-102 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeSO.sub.2-5-Pyr O 4-103 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtSO.sub.2-5-Pyr O 4-104 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhSO.sub.2NMe-5-Pyr O 4-105 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Bz-5-Pyr O 4-106 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhO-5-Pyr O 4-107 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhS-5-Pyr O 4-108 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhSO.sub.2-5-Pyr O 4-109 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Me-6-Pyr O 4-110 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr O 4-111 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-6-Pyr O 4-112 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-6-Pyr O 4-113 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-4-Pym O 4-114 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-4-Pym O 4-115 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeO-4-Pym O 4-116 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtO-4-Pym O 4-117 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrO-4-Pym O 4-118 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeS-4-Pym O 4-119 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtS-4-Pym O 4-120 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrS-4-Pym O 4-121 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 6-MeS-4-Pym O 4-122 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 6-EtS-4-Pym O 4-123 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 6-iPrS-4-Pym O 4-124 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhS-4-Pym O 4-125 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeSO.sub.2-4-Pym O 4-126 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtSO.sub.2-4-Pym O 4-127 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrSO.sub.2-4-Pym O 4-128 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhSO.sub.2-4-Pym O 4-129 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-5-Pym O 4-130 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pym O 4-131 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeO-5-Pym O 4-132 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtO-5-Pym O 4-133 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pym O 4-134 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeS-5-Pym O 4-135 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtS-5-Pym O 4-136 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrS-5-Pym O 4-137 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhS-5-Pym O 4-138 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeSO.sub.2-5-Pym O 4-139 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtSO.sub.2-5-Pym O 4-140 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrSO.sub.2-5-Pym O 4-141 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-PhSO2-5-Pym O 4-142 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ind O 4-143 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 3-Ind O 4-144 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
1-Me-2-Ind O 4-145 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-3-Ind O
4-146 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Bimid O 4-147 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Boxa O 4-148 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 2-Bthiz O 4-149 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
2-Quin O 4-150 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Quin O 4-151 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Quin O 4-152 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 1-iQuin O 4-153 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
3-iQuin O 4-154 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-iQuin O 4-155
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-MeO--Ph O 4-156 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-MeO--Ph O 4-157 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-EtO--Ph O 4-158 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-EtO--Ph O 4-159 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-iPrO--Ph O 4-160 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-iPrO--Ph O 4-161 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-MeS--Ph O 4-162 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-MeS--Ph O 4-163 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-EtS--Ph O 4-164 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-EtS--Ph O 4-165 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-iPrS--Ph O 4-166 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-iPrS--Ph O 4-167 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-MeSO.sub.2--Ph O 4-168 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-MeSO.sub.2--Ph O 4-169 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-EtSO.sub.2--Ph O 4-170 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-EtSO.sub.2--Ph O 4-171 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-iPrSO.sub.2--Ph O 4-172 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-iPrSO.sub.2--Ph O 4-173 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-(1-Me-Imid-4)-Ph O 4-174 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(1-Me-Imid-4)-Ph O 4-175 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1-Me-2-Ph-4-Imid O 4-176 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1,4-di-Me-2-Ph-5-Imid O 4-177 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 1,5-di-Me-2-Ph-4-Imid O 4-178 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3,4-MdO--Ph O 4-179 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-MeO--Ph)--Ph O 4-180 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3,4-MdO--Ph)--Ph O 4-181 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-[PhSO.sub.2N(Me)]--Ph O 4-182 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-[(Pyr-3)SO.sub.2N(Me)]--Ph O
4-183 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(PhSO.sub.2NH)-Ph O
4-184 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-[(Pyr-3)SO.sub.2NH]--Ph
O 4-185 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-[(Pyr-2)SO.sub.2]--Ph
O 4-186 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-[(Pyr-3)SO.sub.2]--Ph
O 4-187 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-[(Pyr-2)SO.sub.2N(Me)]--Ph O 4-188 H (CH.sub.2).sub.2 H H
CH.sub.2 Bu 4-[(Pyr-2)SO.sub.2NH]--Ph O 4-189 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 4-(4-Me--Ph)--Ph O 4-190 H (CH.sub.2).sub.2 H H
CH.sub.2 Bu 4-(4-F--Ph)--Ph O 4-191 H (CH.sub.2).sub.2 H H CH.sub.2
Bu 4-(4-CF.sub.3--Ph)--Ph O 4-192 H (CH.sub.2).sub.2 H H CH.sub.2
Bu 2-[PhSO.sub.2N(Me)]-5-Pyr O 4-193 H (CH.sub.2).sub.2 H H
CH.sub.2 Bu 2-HO-5-Pyr O 4-194 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
2-BzO-5-Pyr O 4-195 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-[(Pyr-4)SO.sub.2]--Ph O 4-196 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-[(Pyr-4)O]--Ph O 4-197 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-[(Pyr-4)S]--Ph O 4-198 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
3-HO--Ph O 4-199 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-HO--Ph O
4-200 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-HO-3,4,6-tri-Me--Ph O
4-201 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-HO-3,5-di-Me--Ph O 4-202
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-AcO--Ph O 4-203 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-AcO--Ph O 4-204 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-Cl--Ph)--Ph O 4-205 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HO-3,5-di-Me--Ph)--Ph O 4-206
H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HO--Ph)--Ph O 4-207 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-OHC--Ph)--Ph O 4-208 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-Dmam-Ph)--Ph O 4-209 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-Dma-Ph)--Ph O 4-210 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HOOC--Ph)--Ph O 4-211 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HOH.sub.2C--Ph)--Ph O 4-212 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO--Ph)--Ph O 4-213 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-HO--Ph)--Ph O 4-214 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-OHC--Ph)--Ph O 4-215 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dmam-Ph)--Ph O 4-216 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Ph)--Ph O 4-217 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-HOOC--Ph)--Ph O 4-218 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-HOH.sub.2C--Ph)--Ph O 4-219 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(2-MeO--Ph)--Ph O 4-220 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(2-HO--Ph)--Ph O 4-221 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(2-OHC--Ph)--Ph O 4-222 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 4-223 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-EtO-Pyr-6)-Ph O 4-224 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-iPrO-Pyr-6)-Ph O 4-225 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 4-226 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dea-Pyr-6)-Ph O 4-227 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-F.sub.3C-Pyr-6)-Ph O 4-228 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-O.sub.2N-Pyr-6)-Ph O 4-229 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Pip-Ph O 4-230 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Dea-Ph O 4-231 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 4-232 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-Cl--Ph)-5-Pyr O 4-233 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 4-234 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-EtO--Ph)-5-Pyr O 4-235 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-iPrO--Ph)-5-Pyr O 4-236 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 4-237 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-AcO--Ph)--Ph O 4-238 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-F--Ph)--Ph O 4-239 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Cl--Ph)--Ph O 4-240 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Me--Ph)--Ph O 4-241 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-AcO--Ph)--Ph O 4-242 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Mc-Pyr-6)-Ph O 4-243 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(3-Et-Pyr-6)-Ph O 4-244 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-Me--Ph)-5-Pyr O 4-245 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-CF.sub.3--Ph)-5-Pyr O 4-246 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-Dma-Ph)-5-Pyr O 4-247 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-F--Ph)-5-Pyr O 4-248 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-Cl--Ph)-5-Pyr O 4-249 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-MeO--Ph)-5-Pyr O 4-250 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-EtO--Ph)-5-Pyr O 4-251 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-iPrO--Ph)-5-Pyr O 4-252 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-Me--Ph)-5-Pyr O 4-253 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-CF.sub.3--Ph)-5-Pyr O 4-254 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(3-Dma-Ph)-5-Pyr O
[0268]
5TABLE 5 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 5-1
H (CH.sub.2).sub.2 H H CH.sub.2 Pen Ph O 5-2 H (CH.sub.2).sub.2 H H
CH.sub.2 Pen 1-Np O 5-3 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Np O
5-4 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Me--Ph O 5-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Et-Ph O 5-6 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 3-iPr--Ph O 5-7 H (CH.sub.2).sub.2 H H CH.sub.2
Pen 4-iPr--Ph O 5-8 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-tBu--Ph O
5-9 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-tBu--Ph O 5-10 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-F--Ph O 5-ll H (CH.sub.2).sub.2
H H CH.sub.2 Pen 4-F--Ph O 5-12 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-Cl--Ph O 5-13 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Br--Ph O 5-14
H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph--Ph O 5-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph O 5-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-BzO--Ph O 5-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Bz-Ph O 5-18 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 3-PhO--Ph O 5-19 H (CH.sub.2).sub.2 H H CH.sub.2
Pen 4-PhO--Ph O 5-20 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-PhS--Ph
O 5-21 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-PhS--Ph O 5-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-PhSO.sub.2--Ph O 5-23 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-PhSO.sub.2--Ph O 5-24 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Imid-1)-Ph O 5-25 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Imid-1)-Ph O 5-26 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Imid-4)-Ph O 5-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Imid-4)-Ph O 5-28 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Fur-2)-Ph O 5-29 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Fur-2)-Ph O 5-30 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Thi-2)-Ph O 5-31 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Thi-2)-Ph O 5-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Thi-3)-Ph O 5-33 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Thi-3)-Ph O 5-34 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Pyr-2)-Ph O 5-35 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph O 5-36 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Pyr-3)-Ph O 5-37 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph O 5-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Pyr-4)-Ph O 5-39 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph O 5-40 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Oxa-2)-Ph O 5-41 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Oxa-2)-Ph O 5-42 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Oxa-4)-Ph O 5-43 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Oxa-4)-Ph O 5-44 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Oxa-5)-Ph O 5-45 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Oxa-5)-Ph O 5-46 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Thiz-2)-Ph O 5-47 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Thiz-2)-Ph O 5-48 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Thiz-4)-Ph O 5-49 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Thiz-4)-Ph O 5-50 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(Thiz-5)-Ph O 5-51 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Thiz-5)-Ph O 5-52 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-2-Pyrr O 5-53 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Ph-2-Pyrr O 5-54 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Bz-2-Pyrr O 5-55 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Me-2-Fur O 5-56 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Ph-2-Fur O 5-57 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Me-2-Thi O 5-58 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Ph-2-Thi O 5-59 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Me-3-Thi O 5-60 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Ph-3-Thi O 5-61 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-3-Pyza O 5-62 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Ph-3-Pyza O 5-63 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-2-Imid O 5-64 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Ph-2-Imid O 5-65 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-4-Imid O 5-66 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Ph-4-Imid O 5-67 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Oxa O 5-68 H (CH.sub.2).sub.2 H
H CH.sub.2 Pen 5-Oxa O 5-69 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
2-Me-4-Oxa O 5-70 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-4-Oxa O
5-71 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Oxa O 5-72 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Oxa O 5-73 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Me-2-Ph-5-Oxa O 5-74 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Me-2-Ph-4-Oxa O 5-75 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Thiz O 5-76 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 5-Thiz O 5-77 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
2-Me-4-Thiz O 5-78 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-4-Thiz
O 5-79 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Thiz O 5-80 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Thiz O 5-81 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Me-2-Ph-5-Thiz O 5-82 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 5-Me-2-Ph-4-Thiz O 5-83 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-4-Pyza O 5-84 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Ph-4-Pyza O 5-85 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-4-Isox O 5-86 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-4-Isox O 5-87 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Pyr O 5-88 H (CH.sub.2).sub.2 H
H CH.sub.2 Pen 3-Pyr O 5-89 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-Pyr O 5-90 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Me-5-Pyr O 5-91
H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Et-5-Pyr O 5-92 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-5-Pyr O 5-93 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Pyr O 5-94 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-BzO-5-Pyr O 5-95 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr O 5-96 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeO-5-Pyr O 5-97 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtO-5-Pyr O 5-98 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrO-5-Pyr O 5-99 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeS-5-Pyr O 5-100 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtS-5-Pyr O 5-101 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhSO.sub.2NH-5-Pyr O 5-102 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeSO.sub.2-5-Pyr O 5-103 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtSO.sub.2-5-Pyr O 5-104 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhSO.sub.2NMe-5-Pyr O 5-105 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Bz-5-Pyr O 5-106 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhO-5-Pyr O 5-107 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhS-5-Pyr O 5-108 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhSO.sub.2-5-Pyr O 5-109 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Me-6-Pyr O 5-110 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr O 5-111 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-6-Pyr O 5-112 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-6-Pyr O 5-113 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-4-Pym O 5-114 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-4-Pym O 5-115 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeO-4-Pym O 5-116 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtO-4-Pym O 5-117 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrO-4-Pym O 5-118 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeS-4-Pym O 5-119 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtS-4-Pym O 5-120 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrS-4-Pym O 5-121 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 6-MeS-4-Pym O 5-122 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 6-EtS-4-Pym O 5-123 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 6-iPrS-4-Pym O 5-124 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhS-4-Pym O 5-125 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeSO.sub.2-4-Pym O 5-126 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtSO.sub.2-4-Pym O 5-127 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrSO.sub.2-4-Pym O 5-128 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhSO.sub.2-4-Pym O 5-129 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Pym O 5-130 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pym O 5-131 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeO-5-Pym O 5-132 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtO-5-Pym O 5-133 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrO-5-Pym O 5-134 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeS-5-Pym O 5-135 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtS-5-Pym O 5-136 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrS-5-Pym O 5-137 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhS-5-Pym O 5-138 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeSO.sub.2-5-Pym O 5-139 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtSO.sub.2-5-Pym O 5-140 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrSO.sub.2-5-Pym O 5-141 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-PhSO.sub.2-5-Pym O 5-142 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ind O 5-143 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 3-Ind O 5-144 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
1-Me-2-Ind O 5-145 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-3-Ind O
5-146 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Bimid O 5-147 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Boxa O 5-148 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 2-Bthiz O 5-149 H (CH.sub.2).sub.2 H H CH.sub.2
Pen 2-Quin O 5-150 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Quin O
5-151 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Quin O 5-152 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-iQuin O 5-153 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-iQuin O 5-154 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-iQuin O 5-155 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-MeO--Ph O 5-156 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-MeO--Ph O 5-157 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-EtO--Ph O 5-158 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-EtO--Ph O 5-159 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-iPrO--Ph O 5-160 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-iPrO--Ph O 5-161 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-MeS--Ph O 5-162 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-MeS--Ph O 5-163 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-EtS--Ph O 5-164 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-EtS--Ph O 5-165 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-iPrS--Ph O 5-166 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-iPrS--Ph O 5-167 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-MeSO.sub.2--Ph O 5-168 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-MeSO.sub.2--Ph O 5-169 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-EtSO.sub.2--Ph O 5-170 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-EtSO.sub.2--Ph O 5-171 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-iPrSO.sub.2--Ph O 5-172 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-iPrSO.sub.2--Ph O 5-173 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-(1-Me-Imid-4)-Ph O 5-174 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(1-Me-Imid-4)-Ph O 5-175 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1-Me-2-Ph-4-Imid O 5-176 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1,4-di-Me-2-Ph-5-Imid O 5-177 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 1,5-di-Me-2-Ph-4-Imid O 5-178 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3,4-MdO--Ph O 5-179 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(4-MeO--Ph)--Ph O 5-180 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(3,4-MdO--Ph)--Ph O 5-181 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-[PhSO.sub.2N(Me)]--Ph O 5-182 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-[(Pyr-3)SO.sub.2N(Me)]--Ph O
5-183 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(PhSO.sub.2NH)-Ph O
5-184 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-[(Pyr-3)SO.sub.2NH]--Ph
O 5-185 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-[(Pyr-2)SO.sub.2]--Ph
O 5-186 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-[(Pyr-3)SO.sub.2]--Ph
O 5-187 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-[(Pyr-2)SO.sub.2N(Me)]--- Ph O 5-188 H (CH.sub.2).sub.2 H H
CH.sub.2 Pen 4-[(Pyr-2)SO.sub.2NH]--Ph O 5-189 H (CH.sub.2).sub.2 H
H CH.sub.2 Pen 4-(4-Me--Ph)--Ph O 5-190 H (CH.sub.2).sub.2 H H
CH.sub.2 Pen 4-(4-F--Ph)--Ph O 5-191 H (CH.sub.2).sub.2 H H
CH.sub.2 Pen 4-(4-CF.sub.3--Ph)--Ph O 5-192 H (CH.sub.2).sub.2 H H
CH.sub.2 Pen 2-[PhSO.sub.2N(Me)]-5-Pyr O 5-193 H (CH.sub.2).sub.2 H
H CH.sub.2 Pen 2-HO-5-Pyr O 5-194 H (CH.sub.2).sub.2 H H CH.sub.2
Pen 2-BzO-5-Pyr O 5-195 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-[(Pyr-4)SO.sub.2]--Ph O 5-196 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-[(Pyr-4)O]--Ph O 5-197 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-[(Pyr-4)S]--Ph O 5-198 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
3-HO--Ph O 5-199 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-HO--Ph O
5-200 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-HO-3,4,6-tri-Me--Ph O
5-201 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-HO-3,5-di-Me--Ph O
5-202 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 3-AcO--Ph O 5-203 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-AcO--Ph O
[0269]
6TABLE 6 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 6-1
H (CH.sub.2).sub.2 H H CH.sub.2 PhO Ph O 6-2 H (CH.sub.2).sub.2 H H
CH.sub.2 PhO 1-Np O 6-3 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Np O
6-4 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Me--Ph O 6-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Et--Ph O 6-6 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 3-iPr--Ph O 6-7 H (CH.sub.2).sub.2 H H CH.sub.2
PhO 4-iPr--Ph O 6-8 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-tBu--Ph O
6-9 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-tBu--Ph O 6-10 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-F--Ph O 6-11 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 4-F--Ph O 6-12 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-Cl--Ph O 6-13 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Br--Ph O 6-14
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph--Ph O 6-15 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph--Ph O 6-16 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-BzO--Ph O 6-17 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Bz-Ph O 6-18 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 3-PhO--Ph O 6-19 H (CH.sub.2).sub.2 H H CH.sub.2
PhO 4-PhO--Ph O 6-20 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-PhS--Ph
O 6-21 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-PhS--Ph O 6-22 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-PhSO.sub.2--Ph O 6-23 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-PhSO.sub.2--Ph O 6-24 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Imid-1)-Ph O 6-25 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Imid-1)-Ph O 6-26 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Imid-4)-Ph O 6-27 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Imid-4)-Ph O 6-28 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Fur-2)-Ph O 6-29 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Fur-2)-Ph O 6-30 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Thi-2)-Ph O 6-31 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Thi-2)-Ph O 6-32 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Thi-3)-Ph O 6-33 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Thi-3)-Ph O 6-34 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Pyr-2)-Ph O 6-35 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph O 6-36 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Pyr-3)-Ph O 6-37 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph O 6-38 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Pyr-4)-Ph O 6-39 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph O 6-40 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Oxa-2)-Ph O 6-41 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Oxa-2)-Ph O 6-42 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Oxa-4)-Ph O 6-43 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Oxa-4)-Ph O 6-44 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Oxa-5)-Ph O 6-45 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Oxa-5)-Ph O 6-46 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Thiz-2)-Ph O 6-47 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Thiz-2)-Ph O 6-48 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Thiz-4)-Ph O 6-49 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Thiz-4)-Ph O 6-50 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(Thiz-5)-Ph O 6-51 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Thiz-5)-Ph O 6-52 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-2-Pyrr O 6-53 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Ph-2-Pyrr O 6-54 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Bz-2-Pyrr O 6-55 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Me-2-Fur O 6-56 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Ph-2-Fur O 6-57 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Me-2-Thi O 6-58 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Ph-2-Thi O 6-59 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Me-3-Thi O 6-60 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Ph-3-Thi O 6-61 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-3-Pyza O 6-62 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Ph-3-Pyza O 6-63 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-2-Imid O 6-64 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Ph-2-Imid O 6-65 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-4-Imid O 6-66 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Ph-4-Imid O 6-67 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Oxa O 6-68 H (CH.sub.2).sub.2 H
H CH.sub.2 PhO 5-Oxa O 6-69 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
2-Me-4-Oxa O 6-70 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-4-Oxa O
6-71 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Oxa O 6-72 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Oxa O 6-73 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Me-2-Ph-5-Oxa O 6-74 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Me-2-Ph-4-Oxa O 6-75 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Thiz O 6-76 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 5-Thiz O 6-77 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
2-Me-4-Thiz O 6-78 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-4-Thiz
O 6-79 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Thiz O 6-80 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Thiz O 6-81 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Me-2-Ph-5-Thiz O 6-82 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 5-Me-2-Ph-4-Thiz O 6-83 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-4-Pyza O 6-84 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Ph-4-Pyza O 6-85 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-4-Isox O 6-86 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-4-Isox O 6-87 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Pyr O 6-88 H (CH.sub.2).sub.2 H
H CH.sub.2 PhO 3-Pyr O 6-89 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-Pyr O 6-90 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Me-5-Pyr O 6-91
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Et-5-Pyr O 6-92 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-5-Pyr O 6-93 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Pyr O 6-94 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-BzO-5-Pyr O 6-95 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr O 6-96 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeO-5-Pyr O 6-97 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtO-5-Pyr O 6-98 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrO-5-Pyr O 6-99 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeS-5-Pyr O 6-100 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtS-5-Pyr O 6-101 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhSO.sub.2NH-5-Pyr O 6-102 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeSO.sub.2-5-Pyr O 6-103 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtSO.sub.2-5-Pyr O 6-104 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhSO.sub.2NMe-5-Pyr O 6-105 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Bz-5-Pyr O 6-106 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhO-5-Pyr O 6-107 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhS-5-Pyr O 6-108 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhSO.sub.2-5-Pyr O 6-109 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Me-6-Pyr O 6-110 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr O 6-111 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-6-Pyr O 6-112 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-6-Pyr O 6-113 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-4-Pym O 6-114 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-4-Pym O 6-115 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeO-4-Pym O 6-116 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtO-4-Pym O 6-117 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrO-4-Pym O 6-118 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeS-4-Pym O 6-119 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtS-4-Pym O 6-120 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrS-4-Pym O 6-121 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 6-MeS-4-Pym O 6-122 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 6-EtS-4-Pym O 6-123 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 6-iPrS-4-Pym O 6-124 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhS-4-Pym O 6-125 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeSO.sub.2-4-Pym O 6-126 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtSO.sub.2-4-Pym O 6-127 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrSO.sub.2-4-Pym O 6-128 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhSO.sub.2-4-Pym O 6-129 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Pym O 6-130 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pym O 6-131 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeO-5-Pym O 6-132 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtO-5-Pym O 6-133 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrO-5-Pym O 6-134 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeS-5-Pym O 6-135 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtS-5-Pym O 6-136 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrS-5-Pym O 6-137 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhS-5-Pym O 6-138 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeSO.sub.2-5-Pym O 6-139 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtSO.sub.2-5-Pym O 6-140 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrSO.sub.2-5-Pym O 6-141 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-PhSO.sub.2-5-Pym O 6-142 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ind O 6-143 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 3-Ind O 6-144 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
1-Me-2-Ind O 6-145 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-3-Ind O
6-146 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Bimid O 6-147 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Boxa O 6-148 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 2-Bthiz O 6-149 H (CH.sub.2).sub.2 H H CH.sub.2
PhO 2-Quin O 6-150 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Quin O
6-151 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Quin O 6-152 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-iQuin O 6-153 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-iQuin O 6-154 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-iQuin O 6-155 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-MeO--Ph O 6-156 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-MeO--Ph O 6-157 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-EtO--Ph O 6-158 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-EtO--Ph O 6-159 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-iPrO--Ph O 6-160 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-iPrO--Ph O 6-161 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-MeS--Ph O 6-162 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-MeS--Ph O 6-163 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-EtS--Ph O 6-164 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-EtS--Ph O 6-165 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-iPrS--Ph O 6-166 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-iPrS--Ph O 6-167 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-MeSO.sub.2--Ph O 6-168 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-MeSO.sub.2--Ph O 6-169 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-EtSO.sub.2--Ph O 6-170 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-EtSO.sub.2--Ph O 6-171 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-iPrSO.sub.2--Ph O 6-172 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-iPrSO.sub.2--Ph O 6-173 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-(1-Me-Imid-4)-Ph O 6-174 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(1-Me-Imid-4)-Ph O 6-175 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1-Me-2-Ph-4-Imid O 6-176 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1,4-di-Me-2-Ph-5-Imid O 6-177 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 1,5-di-Me-2-Ph-4-Imid O 6-178 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3,4-MdO--Ph O 6-179 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-MeO--Ph)--Ph O 6-180 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3,4-MdO--Ph)--Ph O 6-181 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-[PhSO.sub.2N(Me)]--Ph O 6-182 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-[(Pyr-3)SO.sub.2N(Me)]--Ph O
6-183 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(PhSO.sub.2NH)-Ph O
6-184 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-[(Pyr-3)SO.sub.2NH]--Ph
O 6-185 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-[(Pyr-2)SO.sub.2]--Ph
O 6-186 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-[(Pyr-3)SO.sub.2]--Ph
O 6-187 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-[(Pyr-2)SO.sub.2N(Me)]--- Ph O 6-188 H (CH.sub.2).sub.2 H H
CH.sub.2 PhO 4-[(Pyr-2)SO.sub.2NH]--Ph O 6-189 H (CH.sub.2).sub.2 H
H CH.sub.2 PhO 4-(4-Me--Ph)--Ph O 6-190 H (CH.sub.2).sub.2 H H
CH.sub.2 PhO 4-(4-F--Ph)--Ph O 6-191 H (CH.sub.2).sub.2 H H
CH.sub.2 PhO 4-(4-CF.sub.3--Ph)--Ph O 6-192 H (CH.sub.2).sub.2 H H
CH.sub.2 PhO 2-[PhSO.sub.2N(Me)]-5-Pyr O 6-193 H (CH.sub.2).sub.2 H
H CH.sub.2 PhO 2-HO-5-Pyr O 6-194 H (CH.sub.2).sub.2 H H CH.sub.2
PhO 2-BzO-5-Pyr O 6-195 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-[(Pyr-4)SO.sub.2]--Ph O 6-196 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-[(Pyr-4)O]--Ph O 6-197 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-[(Pyr-4)S]--Ph O 6-198 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
3-HO--Ph O 6-199 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-HO--Ph O
6-200 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-HO-3,4,6-tri-Me--Ph O
6-201 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-HO-3,5-di-Me--Ph O
6-202 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 3-AcO--Ph O 6-203 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-AcO--Ph O 6-204 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-Cl--Ph)--Ph O 6-205 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-HO-3,5-di-Me--Ph)--Ph O
6-206 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-HO--Ph)--Ph O 6-207
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-OHF.sub.3--Ph)--Ph O 6-208
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-Dmam-Ph)--Ph O 6-209 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-Dma-Ph)--Ph O 6-210 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-HOOF.sub.3--Ph)--Ph O 6-211
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-HOH.sub.2F.sub.3--Ph)--Ph
O 6-212 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-MeO--Ph)--Ph O
6-213 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-HO--Ph)--Ph O 6-214
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-OHF.sub.3--Ph)--Ph O 6-215
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Dmam-Ph)--Ph O 6-216 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Dma-Ph)--Ph O 6-217 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-HOOF.sub.3--Ph)--Ph O 6-218
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-HOH.sub.2F.sub.3--Ph)--Ph
O 6-219 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(2-MeO--Ph)--Ph O
6-220 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(2-HO--Ph)--Ph O 6-221
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(2-OHF.sub.3--Ph)--Ph O 6-222
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 6-223 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-EtO-Pyr-6)-Ph O 6-224 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-iPrO-Pyr-6)-Ph O 6-225 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 6-226 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Dea-Pyr-6)-Ph O 6-227 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 6-228 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 6-229 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Pip-Ph O 6-230 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Dea-Ph O 6-231 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 6-232 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-Cl--Ph)-5-Pyr O 6-233 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 6-234 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-EtO--Ph)-5-Pyr O 6-235 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-iPrO--Ph)-5-Pyr O 6-236 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-TfpO-5-Pyr O 6-237 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(4-AcO--Ph)--Ph O 6-238 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-F--Ph)--Ph O 6-239 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Cl--Ph)--Ph O 6-240 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Me--Ph)--Ph O 6-241 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-AcO--Ph)--Ph O 6-242 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Me-Pyr-6)-Ph O 6-243 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(3-Et-Pyr-6)-Ph O 6-244 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-Me--Ph)-5-Pyr O 6-245 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 6-246
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(4-Dma-Ph)-5-Pyr O 6-247 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-F--Ph)-5-Pyr O 6-248 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-Cl--Ph)-5-Pyr O 6-249 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-MeO--Ph)-5-Pyr O 6-250 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-EtO--Ph)-5-Pyr O 6-251 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-iPrO--Ph)-5-Pyr O 6-252 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-Me--Ph)-5-Pyr O 6-253 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-CF.sub.3--Ph)-5-Pyr O 6-254
H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-(3-Dma-Ph)-5-Pyr O
[0270]
7TABLE 7 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 7-1
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO Ph O 7-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Np O 7-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Np O 7-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Me--Ph O 7-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Et--Ph O 7-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-iPr--Ph O 7-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-iPr--Ph O 7-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-tBu--Ph O 7-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-tBu--Ph O 7-10 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-F--Ph O 7-ll H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-F--Ph O 7-12 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Cl--Ph O 7-13 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Br--Ph O 7-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Ph--Ph O 7-15 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 7-16 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-BzO--Ph O 7-17 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Bz-Ph O 7-18 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-PhO--Ph O 7-19 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-PhO--Ph O 7-20 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-PhS--Ph O 7-21 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-PhS--Ph O 7-22 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-PhSO.sub.2--Ph O 7-23 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-PhSO.sub.2--Ph O 7-24 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Imid-1)-Ph O 7-25 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Imid-1)-Ph O 7-26 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Imid-4)-Ph O 7-27 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Imid-4)-Ph O 7-28 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Fur-2)-Ph O 7-29 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Fur-2)-Ph O 7-30 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Thi-2)-Ph O 7-31 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Thi-2)-Ph O 7-32 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Thi-3)-Ph O 7-33 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Thi-3)-Ph O 7-34 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Pyr-2)-Ph O 7-35 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 7-36 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Pyr-3)-Ph O 7-37 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph O 7-38 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Pyr-4)-Ph O 7-39 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph O 7-40 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Oxa-2)-Ph O 7-41 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Oxa-2)-Ph O 7-42 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Oxa-4)-Ph O 7-43 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Oxa-4)-Ph O 7-44 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Oxa-5)-Ph O 7-45 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Oxa-5)-Ph O 7-46 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Thiz-2)-Ph O 7-47 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Thiz-2)-Ph O 7-48 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Thiz-4)-Ph O 7-49 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Thiz-4)-Ph O 7-50 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(Thiz-5)-Ph O 7-51 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Thiz-5)-Ph O 7-52 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-2-Pyrr O 7-53 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Ph-2-Pyrr O 7-54 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Bz-2-Pyrr O 7-55 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Me-2-Fur O 7-56 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Ph-2-Fur O 7-57 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Me-2-Thi O 7-58 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Ph-2-Thi O 7-59 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Me-3-Thi O 7-60 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Ph-3-Thi O 7-61 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-3-Pyza O 7-62 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Ph-3-Pyza O 7-63 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-2-Imid O 7-64 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Ph-2-Imid O 7-65 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-4-Imid O 7-66 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Ph-4-Imid O 7-67 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Oxa O 7-68 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Oxa O 7-69 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-4-Oxa O 7-70 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-4-Oxa O 7-71 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Oxa O 7-72 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Oxa O 7-73 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Me-2-Ph-5-Oxa O 7-74 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Me-2-Ph-4-Oxa O 7-75 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Thiz O 7-76 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Thiz O 7-77 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-4-Thiz O 7-78 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-4-Thiz O 7-79 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Thiz O 7-80 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Thiz O 7-81 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Me-2-Ph-5-Thiz O 7-82 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 5-Me-2-Ph-4-Thiz O 7-83 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-4-Pyza O 7-84 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Ph-4-Pyza O 7-85 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-4-Isox O 7-86 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-4-Isox O 7-87 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Pyr O 7-88 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Pyr O 7-89 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Pyr O 7-90 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Me-5-Pyr O 7-91 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Et-5-Pyr O 7-92 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Ph-5-Pyr O 7-93 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr O 7-94 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-BzO-5-Pyr O 7-95 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr O 7-96 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr O 7-97 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr O 7-98 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr O 7-99 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr O 7-100 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr O 7-101 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-PhSO.sub.2NH-5-Pyr O
7-102 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeSO.sub.2-5-Pyr
O 7-103 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
2-EtSO.sub.2-5-Pyr O 7-104 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 2-PhSO.sub.2NMe-5-Pyr O 7-105 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-Bz-5-Pyr O 7-106 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-PhO-5-Pyr O 7-107 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-PhS-5-Pyr O 7-108 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-PhSO.sub.2-5-Pyr O 7-109 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 3-Me-6-Pyr O 7-110 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr O 7-111 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-Me-6-Pyr O 7-112 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-Ph-6-Pyr O 7-113 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-Me-4-Pym O 7-114 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-Ph-4-Pym O 7-115 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-MeO-4-Pym O 7-116 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-EtO-4-Pym O 7-117 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-iPrO-4-Pym O 7-118 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-MeS-4-Pym O 7-119 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-EtS-4-Pym O 7-120 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-iPrS-4-Pym O 7-121 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 6-MeS-4-Pym O 7-122 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 6-EtS-4-Pym O 7-123 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 6-iPrS-4-Pym O 7-124 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-PhS-4-Pym O 7-125 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-MeSO.sub.2-4-Pym O 7-126 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 2-EtSO.sub.2-4-Pym O 7-127 H (CH.sub.2).sub.2
H H CH.sub.2 4-iPr--PhO 2-iPrSO.sub.2-4-Pym O 7-128 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-PhSO.sub.2-4-Pym O 7-129
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pym O 7-130 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pym O 7-131 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pym O 7-132 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pym O 7-133 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pym O 7-134 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pym O 7-135 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pym O 7-136 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrS-5-Pym O 7-137 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-PhS-5-Pym O 7-138 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeSO.sub.2-5-Pym O 7-139
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtSO.sub.2-5-Pym O
7-140 H (CH.sub.2)2 H H CH.sub.2 4-iPr--PhO 2-iPrSO.sub.2-5-Pym O
7-141 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-PhSO.sub.2-5-Pym
O 7-142 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ind O 7-143 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Ind O 7-144 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-2-Ind O 7-145 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-Me-3-Ind O 7-146 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Bimid O 7-147 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Boxa O 7-148 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Bthiz O 7-149 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Quin O 7-150 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Quin O 7-151 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Quin O 7-152 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 1-iQuin O 7-153 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-iQuin O 7-154 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-iQuin O 7-155 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-MeO--Ph O 7-156 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-MeO--Ph O 7-157 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-EtO--Ph O 7-158 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-EtO--Ph O 7-159 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-iPrO--Ph O 7-160 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-iPrO--Ph O 7-161 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-MeS--Ph O 7-162 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-MeS--Ph O 7-163 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-EtS--Ph O 7-164 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-EtS--Ph O 7-165 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-iPrS--Ph O 7-166 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-iPrS--Ph O 7-167 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-MeSO.sub.2--Ph O 7-168 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-MeSO.sub.2--Ph O 7-169 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-EtSO.sub.2--Ph O 7-170 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-EtSO.sub.2--Ph O 7-171 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-iPrSO.sub.2--Ph O 7-172
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-iPrSO.sub.2--Ph O
7-173 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-(1-Me-Imid-4)-Ph
O 7-174 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(1-Me-Imid-4)-Ph O 7-175 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO Me-2-Ph-4-Imid O 7-176 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 1,4-di-Me-2-Ph-5-Imid O 7-177 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 1,5-di-Me-2-Ph-4-Imid O 7-178 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3,4-MdO--Ph O 7-179 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(4-MeO--Ph)--Ph O 7-180
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3,4-MdO--Ph)--Ph O
7-181 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-[PhSO.sub.2N(Me)]--Ph O 7-182 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-[(Pyr-3)-SO.sub.2N(Me)- ]--Ph O 7-183 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(PhSO.sub.2NH)-Ph O
7-184 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-[(Pyr-3)-SO.sub.2NH]--Ph O 7-185 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-[(Pyr-2)SO.sub.2]--Ph O 7-186 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-[(Pyr-3)SO.sub.2]--Ph O 7-187 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-[(Pyr-2)-SO.sub.2N(Me)-
]--Ph O 7-188 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-[(Pyr-2)-SO.sub.2NH]--Ph O 7-189 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(4-Me--Ph)--Ph O 7-190 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(4-F--Ph)--Ph O 7-191 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(4-CF.sub.3--Ph)--Ph O 7-192 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-[PhSO.sub.2N(Me)]-5-Pyr O 7-193 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-HO-5-Pyr O 7-194 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-BzO-5-Pyr O 7-195 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-[(Pyr-4)SO.sub.2]--Ph O
7-196 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-[(Pyr-4)O]--Ph O
7-197 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-[(Pyr-4)S]--Ph O
7-198 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-HO--Ph O 7-199 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-HO--Ph O 7-200 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO HO-3,4,6-tri-Me--Ph O
7-201 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-HO-3,5-di-Me--Ph
O 7-202 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-AcO--Ph O
7-203 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-AcO--Ph O 7-204
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(4-Cl--Ph)--Ph O 7-205
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(4-HO-3,5-di-Me--Ph)--Ph O 7-206 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(4-HO--Ph)--Ph O 7-207 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(4-OHF.sub.3--Ph)--Ph O 7-208 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(4-Dmam-Ph)--Ph O 7-209 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(4-Dma-Ph)--Ph O 7-210 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(4-HOOF.sub.3--Ph)--Ph O 7-211 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(4-HOH.sub.2F.sub.3--Ph)--Ph O 7-212 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(3-MeO--Ph)--Ph O 7-213 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(3-HO--Ph)--Ph O 7-214 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(3-OHF.sub.3--Ph)--Ph O 7-215 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-Dmam-Ph)--Ph O 7-216
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-Dma-Ph)--Ph O 7-217
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-HOOF.sub.3--Ph)--Ph
O 7-218 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(3-HOH.sub.2F.sub.3--Ph)--Ph O 7-219 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(2-MeO--Ph)--Ph O 7-220 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(2-HO--Ph)--Ph O 7-221 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(2-OHC--Ph)--Ph O 7-222 H (CH.sub.2).sub.2
H H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O 7-223 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-EtO-Pyr-6)-Ph O 7-224
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-iPrO-Pyr-6)-Ph O
7-225 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(3-Dma-Pyr-6)-Ph
O 7-226 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(3-Dea-Pyr-6)-Ph O 7-227 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 7-228 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 7-229 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Pip-Ph O 7-230 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Dea-Ph O 7-231 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 7-232
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(4-Cl--Ph)-5-Pyr O
7-233 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
2-(4-MeO--Ph)-5-Pyr O 7-234 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 2-(4-EtO--Ph)-5-Pyr O 7-235 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-(4-iPrO--Ph)-5-Pyr O 7-236 H (CH.sub.2).sub.2
H H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 7-237 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(4-AcO--Ph)--Ph O 7-238 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 4-(3-F--Ph)--Ph O 7-239 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO
4-(3-Cl--Ph)--Ph O 7-240 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(3-Me--Ph)--Ph O 7-241 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
4-(3-AcO--Ph)--Ph O 7-242 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 4-(3-Me-Pyr-6)-Ph O 7-243 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 4-(3-Et-Pyr-6)-Ph O 7-244 H (CH.sub.2).sub.2 H
H CH.sub.2 4-iPr--PhO 2-(4-Me--Ph)-5-Pyr O 7-245 H (CH.sub.2).sub.2
H H CH.sub.2 4-iPr--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 7-246 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(4-Dma-Pd-5-Pyr O 7-247
H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(3-F--Ph)-5-Pyr O
7-248 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(3-Cl--Ph)-5-Pyr
O 7-249 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO
2-(3-MeO--Ph)-5-Pyr O 7-250 H (CH.sub.2).sub.2 H H CH.sub.2
4-iPr--PhO 2-(3-EtO--Ph)-5-Pyr O 7-251 H (CH.sub.2).sub.2 H H
CH.sub.2 4-iPr--PhO 2-(3-iPrO--Ph)-5-Pyr O 7-252 H (CH.sub.2).sub.2
H H CH.sub.2 4-iPr--PhO 2-(3-Me--Ph)-5-Pyr O 7-253 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(3-CF.sub.3--Ph)-5-Pyr O
7-254 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-(3-Dma-Ph)-5-Pyr
O
[0271]
8TABLE 8 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 8-1
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO Ph O 8-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Np O 8-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Np O 8-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Me--Ph O 8-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Et--Ph O 8-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-iPr--Ph O 8-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-iPr--Ph O 8-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-tBu--Ph O 8-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-tBu--Ph O 8-10 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-F--Ph O 8-11 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-F--Ph O 8-12 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Cl--Ph O 8-13 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Br--Ph O 8-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph--Ph O 8-15 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 8-16 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-BzO--Ph O 8-17 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Bz-Ph O 8-18 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-PhO--Ph O 8-19 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-PhO--Ph O 8-20 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-PhS--Ph O 8-21 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-PhS--Ph O 8-22 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-PhSO.sub.2--Ph O 8-23 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-PhSO.sub.2--Ph O 8-24 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Imid-1)-Ph O 8-25 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Imid-1)-Ph O 8-26 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Imid-4)-Ph O 8-27 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Imid-4)-Ph O 8-28 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Fur-2)-Ph O 8-29 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Fur-2)-Ph O 8-30 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Thi-2)-Ph O 8-31 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Thi-2)-Ph O 8-32 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Thi-3)-Ph O 8-33 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Thi-3)-Ph O 8-34 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Pyr-2)-Ph O 8-35 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 8-36 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Pyr-3)-Ph O 8-37 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph O 8-38 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Pyr-4)-Ph O 8-39 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph O 8-40 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Oxa-2)-Ph O 8-41 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Oxa-2)-Ph O 8-42 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Oxa-4)-Ph O 8-43 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Oxa-4)-Ph O 8-44 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Oxa-5)-Ph O 8-45 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Oxa-5)-Ph O 8-46 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Thiz-2)-Ph O 8-47 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Thiz-2)-Ph O 8-48 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Thiz-4)-Ph O 8-49 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Thiz-4)-Ph O 8-50 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(Thiz-5)-Ph O 8-51 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Thiz-5)-Ph O 8-52 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Me-2-Pyrr O 8-53 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Ph-2-Pyrr O 8-54 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Bz-2-Pyrr O 8-55 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Me-2-Fur O 8-56 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Ph-2-Fur O 8-57 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Me-2-Thi O 8-58 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Ph-2-Thi O 8-59 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Me-3-Thi O 8-60 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Ph-3-Thi O 8-61 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Me-3-Pyza O 8-62 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Ph-3-Pyza O 8-63 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Me-2-Imid O 8-64 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Ph-2-Imid O 8-65 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Me-4-Imid O 8-66 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Ph-4-Imid O 8-67 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Oxa O 8-68 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Oxa O 8-69 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-4-Oxa O 8-70 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-4-Oxa O 8-71 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Oxa O 8-72 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Oxa O 8-73 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Me-2-Ph-5-Oxa O 8-74 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Me-2-Ph-4-Oxa O 8-75 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Thiz O 8-76 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Thiz O 8-77 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-4-Thiz O 8-78 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-4-Thiz O 8-79 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Thiz O 8-80 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Thiz O 8-81 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO Me-2-Ph-5-Thiz O 8-82 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 5-Me-2-Ph-4-Thiz O 8-83 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-Me-4-Pyza O 8-84 H
(CH.sub.2).sub.2 H H ch.sub.2 4-MeO--PhO 1-Ph-4-Pyza O 8-85 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-4-Isox O 8-86 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-4-Isox O 8-87 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Pyr O 8-88 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Pyr O 8-89 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Pyr O 8-90 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Me-5-Pyr O 8-91 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Et-5-Pyr O 8-92 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph-5-Pyr O 8-93 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pyr O 8-94 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-BzO-5-Pyr O 8-95 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr O 8-96 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr O 8-97 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr O 8-98 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr O 8-99 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr O 8-100 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr O 8-101 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-PhSO.sub.2NH-5-Pyr O
8-102 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeSO.sub.2-5-Pyr
O 8-103 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-EtSO.sub.2-5-Pyr O 8-104 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 2-PhSO.sub.2NMe-5-Pyr O 8-105 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Bz-5-Pyr O 8-106 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-PhO-5-Pyr O 8-107 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-PhS-5-Pyr O 8-108 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-PhSO.sub.2-5-Pyr O 8-109 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 3-Me-6-Pyr O 8-110 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr O 8-111 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Me-6-Pyr O 8-112 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Ph-6-Pyr O 8-113 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Me-4-Pym O 8-114 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Ph-4-Pym O 8-115 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-MeO-4-Pym O 8-116 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-EtO-4-Pym O 8-117 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-iPrO-4-Pym O 8-118 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-MeS-4-Pym O 8-119 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-EtS-4-Pym O 8-120 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-iPrS-4-Pym O 8-121 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 6-MeS-4-Pym O 8-122 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 6-EtS-4-Pym O 8-123 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 6-iPrS-4-Pym O 8-124 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-PhS-4-Pym O 8-125 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-MeSO.sub.2-4-Pym O 8-126 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 2-EtSO.sub.2-4-Pym O 8-127 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeO--PhO 2-iPrSO.sub.2-4-Pym O 8-128 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-PhSO.sub.2-4-Pym O 8-129
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pym O 8-130 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pym O 8-131 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pym O 8-132 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pym O 8-133 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pym O 8-134 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pym O 8-135 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pym O 8-136 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrS-5-Pym O 8-137 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-PhS-5-Pym O 8-138 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeSO.sub.2-5-Pym O 8-139
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtSO.sub.2-5-Pym O
8-140 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-iPrSO.sub.2-5-Pym O 8-141 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 2-PhSO.sub.2-5-Pym O 8-142 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-Ind O 8-143 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 3-Ind O 8-144 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
1-Me-2-Ind O 8-145 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
1-Me-3-Ind O 8-146 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-Bimid O 8-147 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Boxa O
8-148 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Bthiz O 8-149 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Quin O 8-150 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Quin O 8-151 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Quin O 8-152 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 1-iQuin O 8-153 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-iQuin O 8-154 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-iQuin O 8-155 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-MeO--Ph O 8-156 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-MeO--Ph O 8-157 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-EtO--Ph O 8-158 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-EtO--Ph O 8-159 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-iPrO--Ph O 8-160 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-iPrO--Ph O 8-161 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-MeS--Ph O 8-162 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-MeS--Ph O 8-163 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-EtS--Ph O 8-164 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-EtS--Ph O 8-165 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-iPrS--Ph O 8-166 H
(CH.sub.2).sub.2 H H ch.sub.2 4-MeO--PhO 4-iPrS--Ph O 8-167 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-MeSO.sub.2--Ph O 8-168 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-MeSO.sub.2--Ph O 8-169 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-EtSO.sub.2--Ph O 8-170 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-EtSO.sub.2--Ph O 8-171 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-iPrSO.sub.2--Ph O 8-172
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-iPrSO.sub.2--Ph O
8-173 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-(1-Me-Imid-4)-Ph
O 8-174 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-(1-Me-Imid-4)-Ph O 8-175 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO Me-2-Ph-4-Imid O 8-176 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 1,4-di-Me-2-Ph-5-Imid O 8-177 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 1,5-di-Me-2-Ph-4-Imid O 8-178 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3,4-MdO--Ph O 8-179 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(4-MeO--Ph)--Ph O 8-180
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3,4-MdO--Ph)--Ph O
8-181 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-[PhSO.sub.2N(Me)]--Ph O 8-182 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-[(Pyr-3)-SO.sub.2N(Me)- ]--Ph O 8-183 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(PhSO.sub.2NH)--Ph O
8-184 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-[(Pyr-3)-SO.sub.2NH]--Ph O 8-185 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-[(Pyr-2)SO.sub.2]--Ph O 8-186 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-[(Pyr-3)SO.sub.2]--Ph O 8-187 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-[(Pyr-2)-SO.sub.2N(Me)-
]--Ph O 8-188 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-[(Pyr-2)-SO.sub.2NH]--Ph O 8-189 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(4-Me--Ph)--Ph O 8-190 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(4-F--Ph)--Ph O 8-191 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(4-CF.sub.3--Ph)--Ph O 8-192 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-[PhSO.sub.2N(Me)]-5-Pyr O 8-193 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-HO-5-Pyr O 8-194 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-BzO-5-Pyr O 8-195 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-[(Pyr-4)SO.sub.2]--Ph O
8-196 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-[(Pyr-4)O]--Ph O
8-197 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-[(Pyr-4)S]--Ph O
8-198 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-HO--Ph O 8-199 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-HO--Ph O 8-200 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO HO-3,4,6-tri-Me--Ph O
8-201 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-HO-3,5-di-Me--Ph
O 8-202 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-AcO--Ph O
8-203 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-AcO--Ph O 8-204
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(4-Cl--Ph)--Ph O 8-205
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-(4-HO-3.5-di-Me--Ph)--Ph O 8-206 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(4-HO--Ph)--Ph O 8-207 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(4-OHC--Ph)--Ph O 8-208 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-(4-Dmam-Ph)--Ph O 8-209 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(4-Dma-Ph)--Ph O 8-210 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(4-HOOC--Ph)--Ph O 8-211 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeO--PhO 4-(4-HOH.sub.2C--Ph)--Ph O 8-212 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-MeO--Ph)--Ph O 8-213
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-HO--Ph)--Ph O 8-214
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-OHC--Ph)--Ph O
8-215 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-Dmam-Ph)--Ph
O 8-216 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-Dma-Ph)--Ph
O 8-217 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-(3-HOOC--Ph)--Ph O 8-218 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(3-HOH.sub.2C--Ph)--Ph O 8-219 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-(2-MeO--Ph)--Ph O 8-220 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(2-HO--Ph)--Ph O 8-221 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(2-OHC--Ph)--Ph O 8-222 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 8-223 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-EtO-Pyr-6)-Ph O 8-224
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-iPrO-Pyr-6)-Ph O
8-225 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph
O 8-226 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
4-(3-Dea-Pyr-6)-Ph O 8-227 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 8-228 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 8-229 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Pip-Ph O 8-230 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Dea-Ph O 8-231 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O 8-232
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(4-Cl--Ph)-5-Pyr O
8-233 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-(4-MeO--Ph)-5-Pyr O 8-234 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 2-(4-EtO--Ph)-5-Pyr O 8-235 H (CH.sub.2)2 H H CH.sub.2
4-MeO--PhO 2-(4-iPrO--Ph)-5-Pyr O 8-236 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-TfpO-5-Pyr O 8-237 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-(4-AcO--Ph)--Ph O 8-238 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(3-F--Ph)--Ph O 8-239 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(3-Cl--Ph)--Ph O 8-240 H (CH.sub.2).sub.2 H
H CH.sub.2
4-MeO--PhO 4-(3-Me--Ph)--Ph O 8-241 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 4-(3-AcO--Ph)--Ph O 8-242 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 4-(3-Me-Pyr-6)-Ph O 8-243 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeO--PhO 4-(3-Et-Pyr-6)-Ph O 8-244 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeO--PhO 2-(4-Me--Ph)-5-Pyr O 8-245 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O
8-246 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(4-Dma-Ph)-5-Pyr
O 8-247 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-(3-F--Ph)-5-Pyr O 8-248 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 2-(3-Cl--Ph)-5-Pyr O 8-249 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeO--PhO 2-(3-MeO--Ph)-5-Pyr O 8-250 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeO--PhO 2-(3-EtO--Ph)-5-Pyr O 8-251 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(3-iPrO--Ph)-5-Pyr O
8-252 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-(3-Me--Ph)-5-Pyr
O 8-253 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO
2-(3-CF.sub.3--Ph)-5-Pyr O 8-254 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeO--PhO 2-(3-Dma-Ph)-5-Pyr O
[0272]
9TABLE 9 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y 9-1
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph O 9-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Np O 9-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Np O 9-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Me--Ph O 9-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Et--Ph O 9-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-iPr--Ph O 9-7 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-iPr--Ph O 9-8 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-tBu--Ph O 9-9 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-tBu--Ph O 9-10 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-F--Ph O 9-11 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-F--Ph O 9-12 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Cl--Ph O 9-13 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Br--Ph O 9-14 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph--Ph O 9-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph O 9-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-BzO--Ph O 9-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Bz-Ph O 9-18 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-PhO--Ph O 9-19 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-PhO--Ph O 9-20 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-PhS--Ph O 9-21 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-PhS--Ph O 9-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-PhSO.sub.2--Ph O
9-23 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-PhSO.sub.2--Ph O 9-24 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-(Imid-1)-Ph O 9-25 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Imid-1)-Ph O 9-26 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 3-(Imid-4)-Ph O 9-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Imid-4)-Ph O
9-28 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
3-(Fur-2)-Ph O 9-29 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Fur-2)-Ph O 9-30 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-(Thi-2)-Ph O 9-31 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Thi-2)-Ph O 9-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-(Thi-3)-Ph O
9-33 H (CH.sub.2)2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Thi-3)-Ph O
9-34 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
3-(Pyr-2)-Ph O 9-35 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph O 9-36 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-(Pyr-3)-Ph O 9-37 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph O 9-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-(Pyr-4)-Ph O
9-39 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-4)-Ph O 9-40 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-(Oxa-2)-Ph O 9-41 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Oxa-2)-Ph O 9-42 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 3-(Oxa-4)-Ph O 9-43 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Oxa-4)-Ph O
9-44 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
3-(Oxa-5)-Ph O 9-45 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Oxa-5)-Ph O 9-46 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-(Thiz-2)-Ph O 9-47 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Thiz-2)-Ph O 9-48 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-(Thiz-4)-Ph O
9-49 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Thiz-4)-Ph O 9-50 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-(Thiz-5)-Ph O 9-51 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Thiz-5)-Ph O 9-52 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-2-Pyrr O 9-53 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Ph-2-Pyrr O 9-54
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Bz-2-Pyrr O
9-55 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 5-Me-2-Fur
O 9-56 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
5-Ph-2-Fur O 9-57 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 5-Me-2-Thi O 9-58 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 5-Ph-2-Thi O 9-59 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 5-Me-3-Thi O 9-60 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 5-Ph-3-Thi O 9-61 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-3-Pyza O 9-62
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Ph-3-Pyza O
9-63 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-2-Imid
O 9-64 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
1-Ph-2-Imid O 9-65 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 1-Me-4-Imid O 9-66 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 1-Ph-4-Imid O 9-67 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 4-Oxa O 9-68 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 5-Oxa O 9-69 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-4-Oxa O 9-70 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-4-Oxa O 9-71 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Oxa O 9-72 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Oxa O 9-73
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Me-2-Ph-5-Oxa
O 9-74 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
5-Me-2-Ph-4-Oxa O 9-75 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-Thiz O 9-76 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 5-Thiz O 9-77 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-Me-4-Thiz O 9-78 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-4-Thiz O 9-79 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Thiz O 9-80 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Thiz O 9-81 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Me-2-Ph-5-Thiz O
9-82 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
5-Me-2-Ph-4-Thiz O 9-83 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 1-Me-4-Pyza O 9-84 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 1-Ph-4-Pyza O 9-85 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-4-Isox O 9-86 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-4-Isox O 9-87 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr O 9-88 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr O 9-89 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr O 9-90 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Me-5-Pyr O 9-91
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Et-5-Pyr O
9-92 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-5-Pyr
O 9-93 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-Me-5-Pyr O 9-94 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-BzO-5-Pyr O 9-95 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O 9-96 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr O 9-97 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtO-5-Pyr O 9-98 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr O
9-99 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr
O 9-100 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtS-5-Pyr O 9-101 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-PhSO.sub.2NH-5-Pyr O 9-102 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeSO.sub.2-5-Pyr O 9-103 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtSO.sub.2-5-Pyr
O 9-104 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-PhSO.sub.2NMe-5-Pyr O 9-105 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-Bz-5-Pyr O 9-106 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-PhO-5-Pyr O 9-107 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-PhS-5-Pyr O 9-108 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-PhSO.sub.2-5-Pyr
O 9-109 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
3-Me-6-Pyr O 9-110 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-Ph-6-Pyr O 9-111 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-6-Pyr O 9-112 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-6-Pyr O 9-113 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-4-Pym O 9-114 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-4-Pym O 9-115
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-4-Pym O
9-116 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtO-4-Pym O 9-117 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-4-Pym O 9-118 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-4-Pym O 9-119 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-4-Pym O 9-120 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-iPrS-4-Pym O
9-121 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
6-MeS-4-Pym O 9-122 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 6-EtS-4-Pym O 9-123 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 6-iPrS-4-Pym O 9-124 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-PhS-4-Pym O 9-125 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeSO.sub.2-4-Pym
O 9-126 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtSO.sub.2-4-Pym O 9-127 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrSO.sub.2-4-Pym O 9-128 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-PhSO.sub.2-4-Pym O 9-129 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pym O 9-130
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pym O
9-131 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-MeO-5-Pym O 9-132 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-EtO-5-Pym O 9-133 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-iPrO-5-Pym O 9-134 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pym O 9-135 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pym O
9-136 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-iPrS-5-Pym O 9-137 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-PhS-5-Pym O 9-138 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeSO.sub.2-5-Pym O 9-139 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtSO.sub.2-5-Pym
O 9-140 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-iPrSO.sub.2-5-Pym O 9-141 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-PhSO.sub.2-5-Pym O 9-142 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ind O 9-143 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Ind O 9-144 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-2-Ind O 9-145 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-3-Ind O 9-146 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Bimid O 9-147 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Boxa O 9-148 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Bthiz O 9-149 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Quin O 9-150 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Quin O 9-151 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-Quin O 9-152 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 1-iQuin O 9-153 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-iQuin O 9-154 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-iQuin O 9-155 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-MeO--Ph O 9-156 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 4-MeO--Ph O 9-157 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 3-EtO--Ph O 9-158 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-EtO--Ph O 9-159
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-iPrO--Ph O
9-160 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-iPrO--Ph
O 9-161 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
3-MeS--Ph O 9-162 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-MeS--Ph O 9-163 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-EtS--Ph O 9-164 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 4-EtS--Ph O 9-165 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 3-iPrS--Ph O 9-166 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-iPrS--Ph O 9-167
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-MeSO.sub.2--Ph
O 9-168 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-MeSO.sub.2--Ph O 9-169 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-EtSO.sub.2--Ph O 9-170 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-EtSO.sub.2--Ph O 9-171 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-iPrSO.sub.2--Ph
O 9-172 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-iPrSO.sub.2--Ph O 9-173 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-(1-Me-Imid-4)-Ph O 9-174 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 4-(1-Me-Imid-4)-Ph O 9-175 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 1-Me-2-Ph-4-Imid O
9-176 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
1,4-di-Me-2-Ph-5-Imid O 9-177 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 1,5-di-Me-2-Ph-4-Imid O 9-178 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 3,4-MdO--Ph O 9-179 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(4-MeO--Ph)--Ph
O 9-180 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(3,4-MdO--Ph)--Ph O 9-181 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-[PhSO.sub.2N(Me)]--Ph O 9-182 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-[(Pyr-3)SO.sub.2N(Me)]- --Ph O 9-183 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(PhSO.sub.2NH)-Ph O 9-184 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-[(Pyr-3)SO.sub.2NH]--Ph O 9-185 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-[(Pyr-2)SO.sub.2]--Ph O 9-186 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-[(Pyr-3)SO.sub.2]--Ph O 9-187 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-[(Pyr-2)SO.sub.2N(Me)]--Ph O 9-188 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-[(Pyr-2)SO.sub.2NH]--P- h O 9-189 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(4-Me--Ph)--Ph O 9-190 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(4-F--Ph)--Ph O 9-191 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(4-CF.sub.3--Ph)--Ph O 9-192 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-[PhSO.sub.2N(Me)]-5-Py- r O 9-193 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-HO-5-Pyr O 9-194
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-BzO-5-Pyr O
9-195 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-[(Pyr-4)SO.sub.2]--Ph O 9-196 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-[(Pyr-4)O]--Ph O 9-197 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-[(Pyr-4)S]--Ph O 9-198 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-HO--Ph O 9-199 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-HO--Ph O 9-200 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-HO-3,4,6-tri-Me--Ph O 9-201 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-HO-3,5-di-Me--Ph O 9-202 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 3-AcO--Ph O 9-203 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 4-AcO--Ph O
[0273]
10TABLE 10 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
10-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 Ph O 10-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 1-Np O 10-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Np O 10-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Me--Ph O 10-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Et--Ph O 10-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-iPr--Ph O 10-7 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-iPr--Ph O 10-8 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-tBu--Ph O 10-9 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-tBu--Ph O 10-10
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-F--Ph O 10-11
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-F--Ph O 10-12
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Cl--Ph O 10-13
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Br--Ph O 10-14
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-Ph--Ph O 10-15
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Ph--Ph O 10-16
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-BzO--Ph O
10-17 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Bz-Ph O
10-18 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-PhO--Ph
O 10-19 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-PhO--Ph O 10-20 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-PhS--Ph O 10-21 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-PhS--Ph O 10-22 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 3-PhSO.sub.2--Ph O 10-23 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-PhSO.sub.2--Ph O
10-24 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-(Imid-1)-Ph O 10-25 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(Imid-1)-Ph O 10-26 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-(Imid-4)-Ph O 10-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Imid-4)-Ph O
10-28 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-(Fur-2)-Ph O 10-29 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(Fur-2)-Ph O 10-30 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-(Thi-2)-Ph O 10-31 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Thi-2)-Ph O 10-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-(Thi-3)-Ph O
10-33 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-(Thi-3)-Ph O 10-34 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-(Pyr-2)-Ph O 10-35 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-(Pyr-2)-Ph O 10-36 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 3-(Pyr-3)-Ph O 10-37 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Pyr-3)-Ph O
10-38 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-(Pyr-4)-Ph O 10-39 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(Pyr-4)-Ph O 10-40 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-(Oxa-2)-Ph O 10-41 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Oxa-2)-Ph O 10-42 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-(Oxa-4)-Ph O
10-43 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-(Oxa-4)-Ph O 10-44 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-(Oxa-5)-Ph O 10-45 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-(Oxa-5)-Ph O 10-46 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 3-(Thiz-2)-Ph O 10-47 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Thiz-2)-Ph O
10-48 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-(Thiz-4)-Ph O 10-49 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(Thiz-4)-Ph O 10-50 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-(Thiz-5)-Ph O 10-51 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-(Thiz-5)-Ph O
10-52 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
1-Me-2-Pyrr O 10-53 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 1-Ph-2-Pyrr O 10-54 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 1-Bz-2-Pyrr O 10-55 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 5-Me-2-Fur O 10-56 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 5-Ph-2-Fur O 10-57
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 5-Me-2-Thi O
10-58 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 5-Ph-2-Thi
O 10-59 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
5-Me-3-Thi O 10-60 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 5-Ph-3-Thi O 10-61 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-3-Pyza O 10-62 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 1-Ph-3-Pyza O 10-63 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-2-Imid O
10-64 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
1-Ph-2-Imid O 10-65 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 1-Me-4-Imid O 10-66 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 1-Ph-4-Imid O 10-67 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Oxa O 10-68 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 5-Oxa O 10-69 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-4-Oxa O 10-70 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-4-Oxa O 10-71 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-5-Oxa O 10-72 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-5-Oxa O 10-73
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Me-2-Ph-5-Oxa
O 10-74 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
5-Me-2-Ph-4-Oxa O 10-75 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-Thiz O 10-76 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 5-Thiz O 10-77 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-Me-4-Thiz O 10-78 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-4-Thiz O 10-79 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-5-Thiz O 10-80 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-5-Thiz O
10-81 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
Me-2-Ph-5-Thiz O 10-82 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 Me-2-Ph-4-Thiz O 10-83 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-4-Pyza O 10-84 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 1-Ph-4-Pyza O 10-85 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-4-Isox O
10-86 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-Ph-4-Isox O 10-87 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-Pyr O 10-88 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-Pyr O 10-89 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-Pyr O 10-90 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-Me-5-Pyr O 10-91 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-Et-5-Pyr O 10-92 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 3-Ph-5-Pyr O 10-93 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-5-Pyr O 10-94 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-BzO-5-Pyr O
10-95 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-5-Pyr
O 10-96 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-MeO-5-Pyr O 10-97 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-EtO-5-Pyr O 10-98 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-iPrO-5-Pyr O 10-99 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-MeS-5-Pyr O 10-100 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-EtS-5-Pyr O
10-101 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-PhSO.sub.2NH-5-Pyr O 10-102 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-MeSO.sub.2-5-Pyr O 10-103 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-EtSO.sub.2-5-Pyr O 10-104 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-PhSO.sub.2NMe-5-Pyr O 10-105 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-Bz-5-Pyr O 10-106 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-PhO-5-Pyr O 10-107 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-PhS-5-Pyr O 10-108 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-PhSO.sub.2-5-Pyr
O 10-109 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-Me-6-Pyr O 10-110 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-Ph-6-Pyr O 10-111 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-6-Pyr O 10-112 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-6-Pyr O 10-113 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-4-Pym O
10-114 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-Ph-4-Pym O 10-115 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-MeO-4-Pym O 10-116 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-EtO-4-Pym O 10-117 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-iPrO-4-Pym O 10-118 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-MeS-4-Pym O
10-119 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-EtS-4-Pym O 10-120 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-iPrS-4-Pym O 10-121 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 6-MeS-4-Pym O 10-122 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 6-EtS-4-Pym O 10-123 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 6-iPrS-4-Pym O
10-124 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-PhS-4-Pym O 10-125 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-MeSO.sub.2-4-Pym O 10-126 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-EtSO.sub.2-4-Pym O 10-127 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-iPrSO.sub.2-4-Pym O 10-128 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-PhSO.sub.2-4-Pym O 10-129 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-Me-5-Pym O 10-130 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ph-5-Pym O
10-131 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-MeO-5-Pym O 10-132 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-EtO-5-Pym O 10-133 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-iPrO-5-Pym O 10-134 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-MeS-5-Pym O
10-135 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-EtS-5-Pym O 10-136 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-iPrS-5-Pym O 10-137 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 2-PhS-5-Pym O 10-138 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 2-MeSO.sub.2-5-Pym O 10-139 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-EtSO.sub.2-5-Pym
O 10-140 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-iPrSO.sub.2-5-Pym O 10-141 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-PhSO.sub.2-5-Pym O 10-142 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-Ind O 10-143 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-Ind O 10-144 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-2-Ind O 10-145 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-3-Ind O 10-146 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Bimid O 10-147 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Boxa O 10-148 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Bthiz O 10-149 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-Quin O 10-150 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-Quin O 10-151 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-Quin O 10-152 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 1-iQuin O 10-153 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-iQuin O 10-154 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-iQuin O 10-155 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-MeO--Ph O 10-156
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-MeO--Ph O
10-157 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-EtO--Ph
O 10-158 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-EtO--Ph O 10-159 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-iPrO--Ph O 10-160 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-iPrO--Ph O 10-161 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 3-MeS--Ph O 10-162 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-MeS--Ph O 10-163
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3-EtS--Ph O
10-164 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-EtS--Ph
O 10-165 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-iPrS--Ph O 10-166 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-iPrS--Ph O 10-167 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-MeSO.sub.2--Ph O 10-168 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-MeSO.sub.2--Ph O
10-169 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-EtSO.sub.2--Ph O 10-170 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-EtSO.sub.2--Ph O 10-171 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 3-iPrSO.sub.2--Ph O 10-172 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-iPrSO.sub.2--Ph
O 10-173 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-(1-Me-Imid-4)-Ph O 10-174 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(1-Me-Imid-4)-Ph O 10-175 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 1-Me-2-Ph-4-Imid O 10-176 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
1,4-di-Me-2-Ph-5-Imid O 10-177 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 1,5-di-Me-2-Ph-4-Imid O 10-178 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 3,4-MdO--Ph O
10-179 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-(4-MeO--Ph)--Ph O 10-180 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(3,4-MdO--Ph)--Ph O 10-181 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.4 4-[PhSO.sub.2N(Me)]--Ph O 10-182 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-[(Pyr-3)SO.sub.2N(Me)]--Ph O 10-183 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-(PhSO.sub.2NH)-Ph O 10-184 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-[(Pyr-3)SO.sub.2NH]--Ph O 10-185 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-[(Pyr-2)SO.sub.2]--Ph O 10-186 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-[(Pyr-3)SO.sub.2]--Ph O 10-187 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-[(Pyr-2)SO.sub.2N(Me)]--Ph O 10-188 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-[(Pyr-2)SO.sub.2NH]--Ph O 10-189 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-(4-Me--Ph)--Ph O 10-190 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-(4-F--Ph)--Ph O 10-191 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-(4-CF.sub.3--Ph)--Ph O 10-192 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 2-[PhSO.sub.2N(Me)]-5-Py- r O 10-193 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 2-HO-5-Pyr O
10-194 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
2-BzO-5-Pyr O 10-195 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-[(Pyr-4)SO.sub.2]--Ph O 10-196 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-[(Pyr-4)O]--Ph O
10-197 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
4-[(Pyr-4)S]--Ph O 10-198 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 3-HO--Ph O 10-199 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.4 4-HO--Ph O 10-200 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.4 2-HO-3,4.6-tri-Me--Ph O 10-201 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4 4-HO-3,5-di-Me--Ph
O 10-202 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.4
3-AcO--Ph O 10-203 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.4 4-AcO--Ph O
[0274]
11TABLE 11 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
11-1 H (CH.sub.2).sub.2 H H CH.sub.2 Et Ph O 11-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-Me--Ph O 11-3 H (CH.sub.2).sub.2
H H CH.sub.2 Et 4-F--Ph O 11-4 H (CH.sub.2).sub.2 H H CH.sub.2 Et
4-Bz-Ph O 11-5 H (CH.sub.2).sub.2 H H CH.sub.2 Et 4-Ph--Ph O 11-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-PhO--Ph O 11-7 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-PhS--Ph O 11-8 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-PhSO.sub.2--Ph O 11-9 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-PhSO.sub.2NH--Ph O 11-10 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-PhSO.sub.2NMe--Ph O 11-11 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)-Ph O 11-12 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-3)-Ph O 11-13 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)-Ph O 11-14 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)O--Ph O 11-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)O--Ph O 11-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)S--Ph O 11-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)S--Ph O 11-18 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)SO.sub.2--Ph O 11-19 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)SO.sub.2--Ph O 11-20 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)SO.sub.2NH--Ph O 11-21 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)SO.sub.2NH--Ph O 11-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-2)SO.sub.2NMe--Ph O 11-23 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 4-(Pyr-4)SO.sub.2NMe--Ph O 11-24 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-Pyr O 11-25 H (CH.sub.2).sub.2 H
H CH.sub.2 Et 3-Pyr O 11-26 H (CH.sub.2).sub.2 H H CH.sub.2 Et
4-Pyr O 11-27 H (CH.sub.2).sub.2 H H CH.sub.2 Et 2-Me-5-Pyr O 11-28
H (CH.sub.2).sub.2 H H CH.sub.2 Et 2-Me-3-Pyr O 11-29 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-MeO-5-Pyr O 11-30 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-EtO-5-Pyr O 11-31 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-iPrO-5-Pyr O 11-32 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-MeS-5-Pyr O 11-33 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-EtS-5-Pyr O 11-34 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-MeSO.sub.2-5-Pyr O 11-35 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-EtSO.sub.2-5-Pyr O 11-36 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-Bz-5-Pyr O 11-37 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-Ph-5-Pyr O 11-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 3-Ph-6-Pyr O 11-39 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-PhO-5-Pyr O 11-40 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-PhS-5-Pyr O 11-41 H
(CH.sub.2).sub.2 H H CH.sub.2 Et 2-PhSO.sub.2-5-Pyr O
[0275]
12TABLE 12 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
12-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS Ph O 12-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Me--Ph O 12-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-F--Ph O 12-4 H (CH.sub.2).sub.2
H H CH.sub.2 MeS 4-Bz-Ph O 12-5 H (CH.sub.2).sub.2 H H CH.sub.2 MeS
4-Ph--Ph O 12-6 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-PhO--Ph O
12-7 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-PhS--Ph O 12-8 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-PhSO.sub.2--Ph O 12-9 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-PhSO.sub.2NH--Ph O 12-10 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-PhSO.sub.2NMe--Ph O 12-11 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph O 12-12 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph O 12-13 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph O 12-14 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)O--Ph O 12-15 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)O--Ph O 12-16 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)S--Ph O 12-17 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)S--Ph O 12-18 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)SO.sub.2--Ph O 12-19 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)SO.sub.2--Ph O 12-20 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)SO.sub.2NH--Ph O 12-21 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)SO.sub.2NH--Ph O 12-22 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)SO.sub.2NMe--Ph O 12-23
H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)SO.sub.2NMe--Ph O
12-24 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Pyr O 12-25 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Pyr O 12-26 H (CH.sub.2).sub.2
H H CH.sub.2 MeS 4-Pyr O 12-27 H (CH.sub.2).sub.2 H H CH.sub.2 MeS
2-Me-5-Pyr O 12-28 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Me-3-Pyr O
12-29 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeO-5-Pyr O 12-30 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtO-5-Pyr O 12-31 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-iPrO-5-Pyr O 12-32 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeS-5-Pyr O 12-33 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtS-5-Pyr O 12-34 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeSO.sub.2-5-Pyr O 12-35 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtSO.sub.2-5-Pyr O 12-36 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Bz-5-Pyr O 12-37 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr O 12-38 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr O 12-39 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-PhO-5-Pyr O 12-40 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-PhS-5-Pyr O 12-41 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-PhSO.sub.2-5-Pyr O
[0276]
13TABLE 13 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
13-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtS Ph O 13-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-Me--Ph O 13-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-F--Ph O 13-4 H (CH.sub.2).sub.2
H H CH.sub.2 EtS 4-Bz-Ph O 13-5 H (CH.sub.2).sub.2 H H CH.sub.2 EtS
4-Ph--Ph O 13-6 H (CH.sub.2).sub.2 H H CH.sub.2 EtS 4-PhO--Ph O
13-7 H (CH.sub.2).sub.2 H H CH.sub.2 EtS 4-PhS--Ph O 13-8 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-PhSO.sub.2--Ph O 13-9 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-PhSO.sub.2NH--Ph O 13-10 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-PhSO.sub.2NMe--Ph O 13-11 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)-Ph O 13-12 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-3)-Ph O 13-13 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)-Ph O 13-14 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)O--Ph O 13-15 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)O--Ph O 13-16 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)S--Ph O 13-17 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)S--Ph O 13-18 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)SO.sub.2--Ph O 13-19 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)SO.sub.2--Ph O 13-20 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)SO.sub.2NH--Ph O 13-21 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)SO.sub.2NH--Ph O 13-22 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-2)SO2NMe--Ph O 13-23 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 4-(Pyr-4)SO.sub.2NMe--Ph O 13-24
H (CH.sub.2).sub.2 H H CH.sub.2 EtS 2-Pyr O 13-25 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 3-Pyr O 13-26 H (CH.sub.2).sub.2
H H CH.sub.2 EtS 4-Pyr O 13-27 H (CH.sub.2).sub.2 H H CH.sub.2 EtS
2-Me-5-Pyr O 13-28 H (CH.sub.2).sub.2 H H CH.sub.2 EtS 2-Me-3-Pyr O
13-29 H (CH.sub.2).sub.2 H H CH.sub.2 EtS 2-MeO-5-Pyr O 13-30 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-EtO-5-Pyr O 13-31 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-iPrO-5-Pyr O 13-32 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-MeS-5-Pyr O 13-33 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-EtS-5-Pyr O 13-34 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-MeSO.sub.2-5-Pyr O 13-35 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-EtSO.sub.2-5-Pyr O 13-36 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-Bz-5-Pyr O 13-37 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-Ph-5-Pyr O 13-38 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 3-Ph-6-Pyr O 13-39 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-PhO-5-Pyr O 13-40 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-PhS-5-Pyr O 13-41 H
(CH.sub.2).sub.2 H H CH.sub.2 EtS 2-PhSO.sub.2-5-Pyr O
[0277]
14TABLE 14 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
14-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO Ph O 14-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-Me--Ph O 14-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-F--Ph O 14-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-Bz-Ph O 14-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-Ph--Ph O 14-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-PhO--Ph O 14-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-PhS--Ph O 14-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-PhSO.sub.2--Ph O 14-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-PhSO.sub.2NH--Ph O 14-10
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-PhSO.sub.2NMe--Ph O
14-11 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-2)-Ph O
14-12 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-3)-Ph O
14-13 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-4)-Ph O
14-14 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-2)O--Ph O
14-15 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-4)O--Ph O
14-16 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-2)S--Ph O
14-17 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-4)S--Ph O
14-18 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-(Pyr-2)SO.sub.2--Ph O 14-19 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 4-(Pyr-4)SO.sub.2--Ph O 14-20 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(Pyr-2)SO.sub.2NH--Ph O 14-21 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(Pyr-4)SO.sub.2NH--Ph O
14-22 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-(Pyr-2)SO.sub.2NMe--Ph O 14-23 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 4-(Pyr-4)SO.sub.2NMe--Ph O 14-24 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 2-Pyr O 14-25 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 3-Pyr O 14-26 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-Pyr O 14-27 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-Me-5-Pyr
O 14-28 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-Me-3-Pyr O
14-29 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-MeO-5-Pyr O 14-30
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-EtO-5-Pyr O 14-31 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-iPrO-5-Pyr O 14-32 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-MeS-5-Pyr O 14-33 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-EtS-5-Pyr O 14-34 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-MeSO.sub.2-5-Pyr O 14-35
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-EtSO.sub.2-5-Pyr O
14-36 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-Bz-5-Pyr O 14-37
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-Ph-5-Pyr O 14-38 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 3-Ph-6-Pyr O 14-39 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-PhO-5-Pyr O 14-40 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-PhS-5-Pyr O 14-41 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-PhSO.sub.2-5-Pyr O 14-42
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(4-Me--Ph)--Ph O 14-43
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(4-CF.sub.3--Ph)--Ph O
14-44 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(4-F--Ph)--Ph O
14-45 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(4-Cl--Ph)--Ph O
14-46 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-(4-HO-3,5-di-Me--Ph)--P- h O 14-47 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-MeO--Ph)--Ph O 14-48 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-HO--Ph)--Ph O 14-49 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-OHC--Ph)--Ph O 14-50 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-Dmam-Ph)--Ph O 14-51 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-Dma-Ph)--Ph O 14-52 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(4-HOOC--Ph)--Ph O 14-53 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Me--PhO 4-(4-HOH.sub.2C--Ph)--Ph O 14-54 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-MeO--Ph)--Ph O 14-55 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-HO--Ph)--Ph O 14-56 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-OHC--Ph)--Ph O 14-57 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Dmam-Ph)--Ph O 14-58 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Dma-Ph)--Ph O 14-59 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-HOOC--Ph)--Ph O 14-60
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-HOH.sub.2C--Ph)--Ph
O 14-61 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(2-MeO--Ph)--Ph
O 14-62 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(2-HO--Ph)--Ph
O 14-63 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(2-OHC--Ph)--Ph
O 14-64 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-(3-MeO-Pyr-6)-Ph O 14-65 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 4-(3-EtO-Pyr-6)-Ph O 14-66 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 4-(3-iPrO-Pyr-6)-Ph O 14-67 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 14-68 H (CH.sub.2).sub.2
H H CH.sub.2 4-Me--PhO 4-(3-Dea-Pyr-6)-Ph O 14-69 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O
14-70 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
4-(3-O.sub.2N-Pyr-3)-Ph O 14-71 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 4-Pip-Ph O 14-72 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 4-Dea-Ph O 14-73 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 2-(4-F--Ph)-5-Pyr O 14-74 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 2-(4-Cl--Ph)-5-Pyr O 14-75 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 2-(4-MeO--Ph)-5-Pyr O 14-76 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Me--PhO 2-(4-EtO--Ph)-5-Pyr O 14-77 H (CH.sub.2).sub.2
H H CH.sub.2 4-Me--PhO 2-(4-iPrO--Ph)-5-Pyr O 14-78 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-TfpO-5-Pyr O 14-79 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(4-AcO--Ph)--Ph O 14-80 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-F--Ph)--Ph O 14-81 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Cl--Ph)--Ph O 14-82 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Me--Ph)--Ph O 14-83 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-AcO--Ph)--Ph O 14-84 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Me-Pyr-6)-Ph O 14-85 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 4-(3-Et-Pyr-6)-Ph O 14-86 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-(4-Me--Ph)-5-Pyr O 14-87
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-(4-CF.sub.3--Ph)-5-Pyr
O 14-88 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
2-(4-Dma-Ph)-5-Pyr O 14-89 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 2-(3-F--Ph)-5-Pyr O 14-90 H (CH.sub.2).sub.2 H H CH.sub.2
4-Me--PhO 2-(3-Cl--Ph)-5-Pyr O 14-91 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Me--PhO 2-(3-MeO--Ph)-5-Pyr O 14-92 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Me--PhO 2-(3-EtO--Ph)-5-Pyr O 14-93 H (CH.sub.2).sub.2
H H CH.sub.2 4-Me--PhO 2-(3-iPrO--Ph)-5-Pyr O 14-94 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-(3-Me--Ph)-5-Pyr O 14-95
H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO 2-(3-CF.sub.3--Ph)-5-Pyr
O 14-96 H (CH.sub.2).sub.2 H H CH.sub.2 4-Me--PhO
2-(3-Dma-Ph)-5-Pyr O
[0278]
15TABLE 15 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
15-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph Ph O 15-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-Me--Ph O 15-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-F--Ph O 15-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-Bz-Ph O 15-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-Ph--Ph O 15-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-PhO--Ph O 15-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-PhS--Ph O 15-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-PhSO.sub.2--Ph O 15-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-PhSO.sub.2NH--Ph O 15-10 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-PhSO.sub.2NMe--Ph O 15-11
H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-2)-Ph O 15-12 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-3)-Ph O 15-13 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-4)-Ph O 15-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-2)O--Ph O 15-15 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-4)O--Ph O 15-16 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-2)S--Ph O 15-17 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-4)S--Ph O 15-18 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-2)SO.sub.2--Ph O
15-19 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph
4-(Pyr-4)SO.sub.2--Ph O 15-20 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--Ph 4-(Pyr-2)SO.sub.2NH--Ph O 15-21 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--Ph 4-(Pyr-4)SO.sub.2NH--Ph O 15-22 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-(Pyr-2)SO.sub.2NMe--Ph O
15-23 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph
4-(Pyr-4)SO.sub.2NMe--Ph O 15-24 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--Ph 2-Pyr O 15-25 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph
3-Pyr O 15-26 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 4-Pyr O
15-27 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-Me-5-Pyr O 15-28 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-Me-3-Pyr O 15-29 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-MeO-5-Pyr O 15-30 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-EtO-5-Pyr O 15-31 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-iPrO-5-Pyr O 15-32 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-MeS-5-Pyr O 15-33 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-EtS-5-Pyr O 15-34 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-MeSO.sub.2-5-Pyr O 15-35 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-EtSO.sub.2-5-Pyr O 15-36 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-Bz-5-Pyr O 15-37 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-Ph-5-Pyr O 15-38 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 3-Ph-6-Pyr O 15-39 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-PhO-5-Pyr O 15-40 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-PhS-5-Pyr O 15-41 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--Ph 2-PhSO.sub.2-5-Pyr O 15-42 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(4-Me--Ph)--Ph O 15-43 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(4-CF.sub.3--Ph)--Ph O
15-44 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(4-F--Ph)--Ph O
15-45 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(4-Cl--Ph)--Ph O
15-46 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO
4-(4-HO-3,5-di-Me--Ph)--P- h O 15-47 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-MeO--Ph)--Ph O 15-48 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-HO--Ph)--Ph O 15-49 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-OHC--Ph)--Ph O 15-50 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-Dmam-Ph)--Ph O 15-51 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-Dma-Ph)--Ph O 15-52 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(4-HOOC--Ph)--Ph O 15-53 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Et--PhO 4-(4-HOH.sub.2C--Ph)--Ph O 15-54 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-MeO--Ph)--Ph O 15-55 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-HO--Ph)--Ph O 15-56 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-OHC--Ph)--Ph O 15-57 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-Dmam-Ph)--Ph O 15-58 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-Dma-Ph)--Ph O 15-59 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-HOOC--Ph)--Ph O 15-60
H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-HOH.sub.2C--Ph)--Ph
O 15-61 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(2-MeO--Ph)--Ph
O 15-62 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(2-HO--Ph)--Ph
O 15-63 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(2-OHC--Ph)--Ph
O 15-64 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO
4-(3-MeO-Pyr-6)-Ph O 15-65 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 4-(3-EtO-Pyr-6)-Ph O 15-66 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 4-(3-iPrO-Pyr-6)-Ph O 15-67 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Et--PhO 4-(3-Dma-Pyr-6)-Ph O 15-68 H (CH.sub.2).sub.2
H H CH.sub.2 4-Et--PhO 4-(3-Dea-Pyr-6)-Ph O 15-69 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O
15-70 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 15-71 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 4-Pip-Ph O 15-72 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 4-Dea-Ph O 15-73 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 2-(4-F--Ph)-5-Pyr O 15-74 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 2-(4-Cl--Ph)-5-Pyr O 15-75 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 2-(4-MeO--Ph)-5-Pyr O 15-76 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Et--PhO 2-(4-EtO--Ph)-5-Pyr O 15-77 H (CH.sub.2).sub.2
H H CH.sub.2 4-Et--PhO 2-(4-iPrO--Ph)-5-Pyr O 15-78 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 2-TfpO-5-Pyr O 15-79 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(4-AcO--Ph)--Ph O 15-80 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-F--Ph)--Ph O 15-81 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-Cl--Ph)--Ph O 15-82 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Ei-PhO 4-(3-Me--Ph)--Ph O 15-83 H
(CH.sub.2).sub.2 H H CH.sub.2 4-El-PhO 4-(3-AcO--Ph)--Ph O 15-84 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-Me-Pyr-6)-Ph O 15-85 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 4-(3-Et-Pyr-6)-Ph O 15-86 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 2-(4-Me--Ph)-5-Pyr O 15-87
H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 2-(4-CF.sub.3--Ph)-5-Pyr
O 15-88 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO
2-(4-Dma-Ph)-5-Pyr O 15-89 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 2-(3-F--Ph)-5-Pyr O 15-90 H (CH.sub.2).sub.2 H H CH.sub.2
4-Et--PhO 2-(3-Cl--Ph)-5-Pyr O 15-91 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Et--PhO 2-(3-MeO--Ph)-5-Pyr O 15-92 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Et--PhO 2-(3-EtO--Ph)-5-Pyr O 15-93 H (CH.sub.2).sub.2
H H CH.sub.2 4-Et--PhO 2-(3-iPrO--Ph)-5-Pyr O 15-94 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 2-(3-Me--Ph)-5-Pyr O 15-95
H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO 2-(3-CF.sub.3--Ph)-5-Pyr
O 15-96 H (CH.sub.2).sub.2 H H CH.sub.2 4-Et--PhO
2-(3-Dma-Ph)-5-Pyr O
[0279]
16TABLE 16 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
16-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 Ph O 16-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-Me--Ph O 16-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-F--Ph O 16-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-Bz-Ph 0 16-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-Ph--Ph O 16-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-PhO--Ph O 16-7 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-PhS--Ph O 16-8 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-PhSO.sub.2--Ph O
16-9 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
4-PhSO.sub.2NH--Ph O 16-10 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 4-PhSO.sub.2NMe--Ph O 16-11 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.2 4-(Pyr-2)-Ph O 16-12 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-(Pyr-3)-Ph O
16-13 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
4-(Pyr-4)-Ph O 16-14 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 4-(Pyr-2)O--Ph O 16-15 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.2 4-(Pyr-4)O--Ph O 16-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-(Pyr-2)S--Ph O
16-17 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
4-(Pyr-4)S--Ph O 16-18 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 4-(Pyr-2)SO.sub.2--Ph O 16-19 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.2 4-(Pyr-4)SO.sub.2--Ph O 16-20 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
4-(Pyr-2)SO.sub.2NH--Ph O 16-21 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 4-(Pyr-4)SO.sub.2NH--Ph O 16-22 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
4-(Pyr-2)SO.sub.2NMe--Ph O 16-23 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 4-(Pyr-4)SO.sub.2NMe--Ph O 16-24 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 2-Pyr O 16-25 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 3-Pyr O 16-26 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 4-Pyr O 16-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 2-Me-5-Pyr O 16-28
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 2-Me-3-Pyr O
16-29 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
2-MeO-5-Pyr O 16-30 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 2-EtO-5-Pyr O 16-31 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.2 2-iPrO-5-Pyr O 16-32 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.2 2-MeS-5-Pyr O 16-33 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 2-EtS-5-Pyr O
16-34 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
2-MeSO.sub.2-5-Pyr O 16-35 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 2-EtSO.sub.2-5-Pyr O 16-36 H (CH.sub.2).sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.2 2-Bz-5-Pyr O 16-37 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.2 2-Ph-5-Pyr O 16-38 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 3-Ph-6-Pyr O 16-39
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2 2-PhO-5-Pyr O
16-40 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.2
2-PhS-5-Pyr O 16-41 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.2 2-PhSO.sub.2-5-Pyr O
[0280]
17TABLE 17 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
17-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS Ph O 17-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Me--Ph O 17-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-F--Ph O 17-4 H (CH.sub.2).sub.2
H H CH.sub.2 PhS 4-Bz-Ph O 17-5 H (CH.sub.2).sub.2 H H CH.sub.2 PhS
4-Ph--Ph O 17-6 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-PhO--Ph O
17-7 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-PhS--Ph O 17-8 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-PhSO.sub.2--Ph O 17-9 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-PhSO.sub.2NH--Ph O 17-10 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-PhSO.sub.2NMe--Ph O 17-11 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph O 17-12 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph O 17-13 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph O 17-14 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)O--Ph O 17-15 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)O--Ph O 17-16 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)S--Ph O 17-17 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)S--Ph O 17-18 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)SO.sub.2--Ph O 17-19 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)SO.sub.2--Ph O 17-20 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)SO.sub.2NH--Ph O 17-21 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)SO.sub.2NH--Ph O 17-22 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)SO.sub.2NMe--Ph O 17-23
H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)SO.sub.2NMe--Ph O
17-24 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Pyr O 17-25 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Pyr O 17-26 H (CH.sub.2).sub.2
H H CH.sub.2 PhS 4-Pyr O 17-27 H (CH.sub.2).sub.2 H H CH.sub.2 PhS
2-Me-5-Pyr O 17-28 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Me-3-Pyr O
17-29 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeO-5-Pyr O 17-30 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtO-5-Pyr O 17-31 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-iPrO-5-Pyr O 17-32 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeS-5-Pyr O 17-33 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtS-5-Pyr O 17-34 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeSO.sub.2-5-Pyr O 17-35 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtSO.sub.2-5-Pyr O 17-36 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Bz-5-Pyr O 17-37 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr O 17-38 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr O 17-39 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-PhO-5-Pyr O 17-40 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-PhS-5-Pyr O 17-41 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-PhSO.sub.2-5-Pyr O 17-42 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-Me--Ph)--Ph O 17-43 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-CF.sub.3--Ph)--Ph O 17-44 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-F--Ph)--Ph O 17-45 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-Cl--Ph)--Ph O 17-46 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-HO-3,5-di-Me--Ph)--Ph O
17-47 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-MeO--Ph)--Ph O 17-48
H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-HO--Ph)--Ph O 17-49 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-OHC--Ph)--Ph O 17-50 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-Dmam-Ph)--Ph O 17-51 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-Dma-Ph)--Ph O 17-52 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-HOOC--Ph)--Ph O 17-53 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(4-HOH.sub.2C--Ph)--Ph O 17-54
H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-MeO--Ph)--Ph O 17-55 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-HO--Ph)--Ph O 17-56 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-OHC--Ph)--Ph O 17-57 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-Dmam-Ph)--Ph O 17-58 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-Dma-Ph)--Ph O 17-59 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-HOOC--Ph)--Ph O 17-60 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-HOH.sub.2C--Ph)--Ph O 17-61
H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(2-MeO--Ph)--Ph O 17-62 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(2-HO--Ph)--Ph O 17-63 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(2-OHC--Ph)--Ph O 17-64 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-MeO-Pyr-6)-Ph O 17-65 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-EtO-Pyr-6)-Ph O 17-66 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-iPrO-Pyr-6)-Ph O 17-67 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-Dma-Pyr-6)-Ph O 17-68 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-Dea-Pyr-6)-Ph O 17-69 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-F.sub.3C-Pyr-6)-Ph O 17-70 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(3-O.sub.2N-Pyr-6)-Ph O 17-71 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Pip-Ph O 17-72 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Dea-Ph O 17-73 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-(4-F--Ph)-5-Pyr O 17-74 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-(4-Cl--Ph)-5-Pyr O 17-75 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-(4-MeO--Ph)-5-Pyr O 17-76 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-(4-EtO--Ph)-5-Pyr O 17-77 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-(4-iPrO--Ph)-5-Pyr O 17-78 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-TfpO-5-Pyr O
[0281]
18TABLE 18 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
18-1 Me (CH.sub.2).sub.2 H H CH.sub.2 EtO Ph O 18-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph O 18-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph O 18-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph O 18-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph O 18-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Pyr O 18-7 Me (CH.sub.2).sub.2
H H CH.sub.2 EtO 3-Pyr O 18-8 Me (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-Pyr O 18-9 Me (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Pyr O
18-10 Me (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-3-Pyr O 18-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeO-5-Pyr O 18-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtO-5-Pyr O 18-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrO-5-Pyr O 18-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeS-5-Pyr O 18-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtS-5-Pyr O 18-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr O 18-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr O
[0282]
19TABLE 19 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
19-1 Me (CH.sub.2).sub.2 H H CH.sub.2 Pr Ph O 19-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph--Ph O 19-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph O 19-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph O 19-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph O 19-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Pyr O 19-7 Me (CH.sub.2).sub.2 H
H CH.sub.2 Pr 3-Pyr O 19-8 Me (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-Pyr O 19-9 Me (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Pyr O 19-10
Me (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-3-Pyr O 19-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeO-5-Pyr O 19-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtO-5-Pyr O 19-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pyr O 19-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeS-5-Pyr O 19-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtS-5-Pyr O 19-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr O 19-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr O
[0283]
20TABLE 20 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
20-1 Me (CH.sub.2).sub.2 H H CH.sub.2 Bu Ph O 20-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 20-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Pyr O 20-7 Me (CH.sub.2).sub.2 H
H CH.sub.2 Bu 3-Pyr O 20-8 Me (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-Pyr O 20-9 Me (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-5-Pyr O 20-10
Me (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Me-3-Pyr O 20-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeO-5-Pyr O 20-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtO-5-Pyr O 20-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pyr O 20-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeS-5-Pyr O 20-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtS-5-Pyr O 20-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr O 20-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr O 20-18 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-Me--Ph)--Ph O 20-19 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-F--Ph)--Ph O 20-20 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HO-3,5-di-Me--Ph)--Ph O 20-21
Me (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-MeO--Ph)--Ph O 20-22 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-HO--Ph)--Ph O 20-23 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-OHC--Ph)--Ph O 20-24 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(4-Dma-Ph)--Ph O 20-25 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO--Ph)--Ph O 20-26 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-HO--Ph)--Ph O 20-27 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Ph)--Ph O 20-28 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(2-MeO--Ph)--Ph O 20-29 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(2-HO--Ph)--Ph O 20-30 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-31 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-EtO-Pyr-6)-Ph O 20-32 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-iPrO-Pyr-6)-Ph O 20-33 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-34 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dea-Pyr-6)-Ph O 20-35 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-F.sub.3C-Pyr-6)-Ph O 20-36 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-O.sub.2N-Pyr-6)-Ph O 20-37 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-38 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-Cl--Ph)-5-Pyr O 20-39 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-40 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-EtO--Ph)-5-Pyr O 20-41 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-iPrO--Ph)-5-Pyr O 20-42 Me
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 20-43 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 20-44 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-45 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-46 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-47 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-48 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-49 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-50 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-51 Et
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 20-52 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 20-53 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-54 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-55 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-56 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-57 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-58 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-59 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-60 Bu
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 20-61 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 20-62 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-63 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-64 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-65 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-66 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-67 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-68 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-69 Bz
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 20-70 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph O 20-71 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-72 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-73 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-74 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-75 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-76 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-77 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-78 PPr
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-TfpO-5-Pyr O 20-79 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-Ph--Ph O 20-80 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 20-81 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 20-82 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 20-83 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 20-84 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 20-85 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 20-86 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 20-87 Me
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-TfpO-5-Pyr O
[0284]
21TABLE 21 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
21-1 Me (CH.sub.2).sub.2 H H CH.sub.2 Pen Ph O 21-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph O 21-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph O 21-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph O 21-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph O 21-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Pyr O 21-7 Me (CH.sub.2).sub.2
H H CH.sub.2 Pen 3-Pyr O 21-8 Me (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-Pyr O 21-9 Me (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Pyr O
21-10 Me (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-3-Pyr O 21-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeO-5-Pyr O 21-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtO-5-Pyr O 21-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrO-5-Pyr O 21-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeS-5-Pyr O 21-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtS-5-Pyr O 21-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr O 21-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr O
[0285]
22TABLE 22 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
22-1 Me (CH.sub.2).sub.2 H H CH.sub.2 MeS Ph O 22-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph--Ph O 22-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph O 22-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph O 22-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph O 22-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Pyr O 22-7 Me (CH.sub.2).sub.2
H H CH.sub.2 MeS 3-Pyr O 22-8 Me (CH.sub.2).sub.2 H H CH.sub.2 MeS
4-Pyr O 22-9 Me (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Me-5-Pyr O
22-10 Me (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Me-3-Pyr O 22-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeO-5-Pyr O 22-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtO-5-Pyr O 22-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-iPrO-5-Pyr O 22-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeS-5-Pyr O 22-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtS-5-Pyr O 22-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr O 22-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr O
[0286]
23TABLE 23 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
23-1 Me (CH.sub.2).sub.2 H H CH.sub.2 PhO Ph O 23-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph--Ph O 23-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph O 23-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph O 23-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph O 23-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Pyr O 23-7 Me (CH.sub.2).sub.2
H H CH.sub.2 PhO 3-Pyr O 23-8 Me (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-Pyr O 23-9 Me (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Pyr O
23-10 Me (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-3-Pyr O 23-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeO-5-Pyr O 23-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtO-5-Pyr O 23-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrO-5-Pyr O 23-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeS-5-Pyr O 23-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtS-5-Pyr O 23-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr O 23-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr O
[0287]
24TABLE 24 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
24-1 Me (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO Ph O 24-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 24-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 24-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph O 24-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph O 24-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Pyr O 24-7 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Pyr O 24-8 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Pyr O 24-9 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr O 24-10 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-3-Pyr O 24-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr O 24-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr O 24-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr O 24-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr O 24-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr O 24-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr O 24-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr O
[0288]
25TABLE 25 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
25-1 Me (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO Ph O 25-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 25-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 25-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph O 25-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph O 25-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Pyr O 25-7 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Pyr O 25-8 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Pyr O 25-9 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pyr O 25-10 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-3-Pyr O 25-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr O 25-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr O 25-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr O 25-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr O 25-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr O 25-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr O 25-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr O
[0289]
26TABLE 26 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
26-1 Me (CH.sub.2).sub.2 H H CH.sub.2 PhS Ph O 26-2 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph--Ph O 26-3 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph O 26-4 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph O 26-5 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph O 26-6 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Pyr O 26-7 Me (CH.sub.2).sub.2
H H CH.sub.2 PhS 3-Pyr O 26-8 Me (CH.sub.2).sub.2 H H CH.sub.2 PhS
4-Pyr O 26-9 Me (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Me-5-Pyr O
26-10 Me (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Me-3-Pyr O 26-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeO-5-Pyr O 26-12 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtO-5-Pyr O 26-13 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-iPrO-5-Pyr O 26-14 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeS-5-Pyr O 26-15 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtS-5-Pyr O 26-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr O 26-17 Me
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr O
[0290]
27TABLE 27 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
27-1 Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph O 27-2
Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph O 27-3
Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph O
27-4 Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-3)-Ph O 27-5 Me (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph O 27-6 Me (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr O 27-7 Me (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr O 27-8 Me (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr O 27-9 Me (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr O 27-10 Me (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr O 27-11 Me
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr O
27-12 Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtO-5-Pyr O 27-13 Me (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr O 27-14 Me (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr O 27-15 Me (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr O 27-16 Me
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O 27-17
Me (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr
O
[0291]
28TABLE 28 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
28-1 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO Ph O 28-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-Ph--Ph O 28-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-2)-Ph O 28-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-3)-Ph O 28-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-4)-Ph O 28-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-Pyr O 28-7 H (CH.sub.2).sub.2
H Me CH.sub.2 EtO 3-Pyr O 28-8 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO
4-Pyr O 28-9 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-Me-5-Pyr O
28-10 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-Me-3-Pyr O 28-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-MeO-5-Pyr O 28-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-EtO-5-Pyr O 28-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-iPrO-5-Pyr O 28-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-MeS-5-Pyr O 28-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-EtS-5-Pyr O 28-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-Ph-5-Pyr O 28-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 3-Ph-6-Pyr O 28-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-Me--Ph)--Ph O 28-19 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-F--Ph)--Ph O 28-20 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-Cl--Ph)--Ph O 28-21 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-HO-3,5-di-Me--Ph)--Ph O
28-22 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-MeO--Ph)--Ph O
28-23 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-HO--Ph)--Ph O 28-24
H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-OHC--Ph)--Ph O 28-25 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(4-Dma-Ph)--Ph O 28-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-MeO--Ph)--Ph O 28-27 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-HO--Ph)--Ph O 28-28 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-Dma-Ph)--Ph O 28-29 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(2-MeO--Ph)--Ph O 28-30 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(2-HO--Ph)--Ph O 28-31 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 28-32 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-EtO-Pyr-6)-Ph O 28-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-iPrO-Pyr-6)-Ph O 28-34 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 28-35 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-Dea-Pyr-6)-Ph O 28-36 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-F.sub.3C-Pyr-6)-Ph O 28-37
H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(3-O.sub.2N-Pyr-6)-Ph O
28-38 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O
28-39 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-(4-Cl--Ph)-5-Pyr O
28-40 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O
28-41 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-(4-EtO--Ph)-5-Pyr O
28-42 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-(4-iPrO--Ph)-5-Pyr O
28-43 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-TfpO-5-Pyr O
[0292]
29TABLE 29 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
29-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Pr Ph O 29-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-Ph--Ph O 29-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-2)-Ph O 29-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-3)-Ph O 29-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-4)-Ph O 29-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-Pyr O 29-7 H (CH.sub.2).sub.2 H
Me CH.sub.2 Pr 3-Pyr O 29-8 H (CH.sub.2).sub.2 H Me CH.sub.2 Pr
4-Pyr O 29-9 H (CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-Me-5-Pyr O 29-10
H (CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-Me-3-Pyr O 29-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-MeO-5-Pyr O 29-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-EtO-5-Pyr O 29-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-iPrO-5-Pyr O 29-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-MeS-5-Pyr O 29-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-EtS-5-Pyr O 29-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-Ph-5-Pyr O 29-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 3-Ph-6-Pyr O 29-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-Me--Ph)--Ph O 29-19 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-F--Ph)--Ph O 29-20 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-Cl--Ph)--Ph O 29-21 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-HO-3,5-di-Me--Ph)--Ph O
29-22 H (CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-MeO--Ph)--Ph O 29-23
H (CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-HO--Ph)--Ph O 29-24 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-OHC--Ph)--Ph O 29-25 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(4-Dma-Ph)--Ph O 29-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-MeO--Ph)--Ph O 29-27 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-HO--Ph)--Ph O 29-28 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-Dma-Ph)--Ph O 29-29 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(2-MeO--Ph)--Ph O 29-30 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(2-HO--Ph)--Ph O 29-31 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 29-32 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-EtO-Pyr-6)-Ph O 29-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-iPrO-Pyr-6)-Ph O 29-34 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 29-35 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-Dea-Pyr-6)-Ph O 29-36 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-F.sub.3C-Pyr-6)-Ph O 29-37 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(3-O.sub.2N-Pyr-6)-Ph O 29-38 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 29-39 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-(4-Cl--Ph)-5-Pyr O 29-40 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 29-41 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-(4-EtO--Ph)-5-Pyr O 29-42 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-(4-iPrO--Ph)-5-Pyr O 29-43 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-TfpO-5-Pyr O
[0293]
30TABLE 30 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
30-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Bu Ph O 30-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-Ph--Ph O 30-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-2)-Ph O 30-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-3)-Ph O 30-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-4)-Ph O 30-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-Pyr O 30-7 H (CH.sub.2).sub.2 H
Me CH.sub.2 Bu 3-Pyr O 30-8 H (CH.sub.2).sub.2 H Me CH.sub.2 Bu
4-Pyr O 30-9 H (CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-Me-5-Pyr O 30-10
H (CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-Me-3-Pyr O 30-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-MeO-5-Pyr O 30-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-EtO-5-Pyr O 30-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-iPrO-5-Pyr O 30-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-MeS-5-Pyr O 30-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-EtS-5-Pyr O 30-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-Ph-5-Pyr O 30-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 3-Ph-6-Pyr O 30-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-Me--Ph)--Ph O 30-19 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-F--Ph)--Ph O 30-20 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-Cl--Ph)--Ph O 30-21 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-HO-3.5-di-Me--Ph)--Ph O
30-22 H (CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-MeO--Ph)--Ph O 30-23
H (CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-HO--Ph)--Ph O 30-24 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-OHC--Ph)--Ph O 30-25 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(4-Dma-Ph)--Ph O 30-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-MeO--Ph)--Ph O 30-27 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-HO--Ph)--Ph O 30-28 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-Dma-Ph)--Ph O 30-29 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(2-MeO--Ph)--Ph O 30-30 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(2-HO--Ph)--Ph O 30-31 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 30-32 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-EtO-Pyr-6)-Ph O 30-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-iPrO-Pyr-6)-Ph O 30-34 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 30-35 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-Dea-Pyr-6)-Ph O 30-36 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-F.sub.3C-Pyr-6)-Ph O 30-37 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(3-O.sub.2N-Pyr-6)-Ph O 30-38 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 30-39 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-(4-Cl--Ph)-5-Pyr O 30-40 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 30-41 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-(4-EtO--Ph)-5-Pyr O 30-42 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-(4-iPrO--Ph)-5-Pyr O 30-43 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-TfpO-5-Pyr O
[0294]
31TABLE 31 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
31-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Pen Ph O 31-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-Ph--Ph O 31-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-2)-Ph O 31-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-3)-Ph O 31-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-4)-Ph O 31-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-Pyr O 31-7 H (CH.sub.2).sub.2
H Me CH.sub.2 Pen 3-Pyr O 31-8 H (CH.sub.2).sub.2 H Me CH.sub.2 Pen
4-Pyr O 31-9 H (CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-Me-5-Pyr O
31-10 H (CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-Me-3-Pyr O 31-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-MeO-5-Pyr O 31-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-EtO-5-Pyr O 31-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-iPrO-5-Pyr O 31-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-MeS-5-Pyr O 31-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-EtS-5-Pyr O 31-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-Ph-5-Pyr O 31-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 3-Ph-6-Pyr O
[0295]
32TABLE 32 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
32-1 H (CH.sub.2).sub.2 H Me CH.sub.2 MeS Ph O 32-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-Ph--Ph O 32-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-2)-Ph O 32-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-3)-Ph O 32-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-4)-Ph O 32-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-Pyr O 32-7 H (CH.sub.2).sub.2
H Me CH.sub.2 MeS 3-Pyr O 32-8 H (CH.sub.2).sub.2 H Me CH.sub.2 MeS
4-Pyr O 32-9 H (CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-Me-5-Pyr O
32-10 H (CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-Me-3-Pyr O 32-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-MeO-5-Pyr O 32-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-EtO-5-Pyr O 32-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-iPrO-5-Pyr O 32-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-MeS-5-Pyr O 32-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-EtS-5-Pyr O 32-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-Ph-5-Pyr O 32-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 3-Ph-6-Pyr O
[0296]
33TABLE 33 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
33-1 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO Ph O 33-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-Ph--Ph O 33-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-2)-Ph O 33-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-3)-Ph O 33-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-4)-Ph O 33-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-Pyr O 33-7 H (CH.sub.2).sub.2
H Me CH.sub.2 PhO 3-Pyr O 33-8 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO
4-Pyr O 33-9 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-Me-5-Pyr O
33-10 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-Me-3-Pyr O 33-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-MeO-5-Pyr O 33-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-EtO-5-Pyr O 33-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-iPrO-5-Pyr O 33-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-MeS-5-Pyr O 33-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-EtS-5-Pyr O 33-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-Ph-5-Pyr O 33-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 3-Ph-6-Pyr O 33-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-Me--Ph)--Ph O 33-19 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-F--Ph)--Ph O 33-20 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-Cl--Ph)--Ph O 33-21 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-HO-3,5-di-Me--Ph)--Ph O
33-22 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-MeO--Ph)--Ph O
33-23 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-HO--Ph)--Ph O 33-24
H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-OHC--Ph)--Ph O 33-25 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-Dma-Ph)--Ph O 33-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-MeO--Ph)--Ph O 33-27 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-HO--Ph)--Ph O 33-28 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Dma-Ph)--Ph O 33-29 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(2-MeO--Ph)--Ph O 33-30 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(2-HO--Ph)--Ph O 33-31 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 33-32 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-EtO-Pyr-6)-Ph O 33-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-iPrO-Pyr-6)-Ph O 33-34 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 33-35 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Dea-Pyr-6)-Ph O 33-36 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 33-37
H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
33-38 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O
33-39 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-Cl--Ph)-5-Pyr O
33-40 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O
33-41 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-EtO--Ph)-5-Pyr O
33-42 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-iPrO--Ph)-5-Pyr O
33-43 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-TfpO-5-Pyr O 33-44 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(4-AcO--Ph)--Ph O 33-45 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-F--Ph)--Ph O 33-46 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Cl--Ph)--Ph O 33-47 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Me--Ph)--Ph O 33-48 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-AcO--Ph)--Ph O 33-49 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Me-Pyr-6)-Ph O 33-50 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(3-Et-Pyr-6)-Ph O 33-51 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-Me--Ph)-5-Pyr O 33-52 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 33-53
H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(4-Dma-Ph)-5-Pyr O 33-54 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-F--Ph)-5-Pyr O 33-55 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-Cl--Ph)-5-Pyr O 33-56 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-MeO--Ph)-5-Pyr O 33-57 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-EtO--Ph)-5-Pyr O 33-58 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-iPrO--Ph)-5-Pyr O 33-59 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-Me--Ph)-5-Pyr O 33-60 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-CF.sub.3--Ph)-5-Pyr O 33-61
H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-(3-Dma-Ph)-5-Pyr O
[0297]
34TABLE 34 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
34-1 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO Ph O 34-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-Ph--Ph O 34-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 34-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph O 34-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph O 34-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-Pyr O 34-7 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 3-Pyr O 34-8 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-Pyr O 34-9 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-Me-5-Pyr O 34-10 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-Me-3-Pyr O 34-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr O 34-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr O 34-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr O 34-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr O 34-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr O 34-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr O 34-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr O 34-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(4-Me--Ph)--Ph O 34-19
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(4-F--Ph)--Ph O 34-20
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(4-Cl--Ph)--Ph O
34-21 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
4-(4-HO-3,5-di-Me--Ph)--Ph O 34-22 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 4-(4-MeO--Ph)--Ph O 34-23 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 4-(4-HO--Ph)--Ph O 34-24 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-iPr--PhO 4-(4-OHC--Ph)--Ph O 34-25 H (CH.sub.2).sub.2
H Me CH.sub.2 4-iPr--PhO 4-(4-Dma-Ph)--Ph O 34-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-MeO--Ph)--Ph O 34-27
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-HO--Ph)--Ph O
34-28 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-Dma-Ph)--Ph
O 34-29 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
4-(2-MeO--Ph)--Ph O 34-30 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 4-(2-HO--Ph)--Ph O 34-31 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O 34-32 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-iPr--PhO 4-(3-EtO-Pyr-6)-Ph O 34-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-iPrO-Pyr-6)-Ph 34-34
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-Dma-Pyr-6)-Ph O
34-35 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
4-(3-Dea-Pyr-6)-Ph O 34-36 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 34-37 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 34-38 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 34-39
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-(4-Cl--Ph)-5-Pyr O
34-40 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
2-(4-MeO--Ph)-5-Pyr O 34-41 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 2-(4-EtO--Ph)-5-Pyr O 34-42 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 2-(4-iPrO--Ph)-5-Pyr O 34-43 H (CH.sub.2).sub.2
H Me CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 34-44 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-iPr--PhO 4-(4-AcO--Ph)--Ph O 34-45 H (CH.sub.2).sub.2
H Me CH.sub.2 4-iPr--PhO 4-(3-F--Ph)--Ph O 34-46 H (CH.sub.2).sub.2
H Me CH.sub.2 4-iPr--PhO 4-(3-Cl--Ph)--Ph O 34-47 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-Me--Ph)--Ph O 34-48
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-AcO--Ph)--Ph O
34-49 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 4-(3-Me-Pyr-6)-Ph
O 34-50 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
4-(3-Et-Pyr-6)-Ph O 34-51 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 2-(4-Me--Ph)-5-Pyr O 34-52 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 34-53 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-(4-Dma-Ph)-5-Pyr O
34-54 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-(3-F--Ph)-5-Pyr
O 34-55 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
2-(3-Cl--Ph)-5-Pyr O 34-56 H (CH.sub.2).sub.2 H Me CH.sub.2
4-iPr--PhO 2-(3-MeO--Ph)-5-Pyr O 34-57 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-iPr--PhO 2-(3-EtO--Ph)-5-Pyr O 34-58 H (CH.sub.2).sub.2
H Me CH.sub.2 4-iPr--PhO 2-(3-iPrO--Ph)-5-Pyr O 34-59 H (CH.sub.2)2
H Me CH.sub.2 4-iPr--PhO 2-(3-Me--Ph)-5-Pyr O 34-60 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO 2-(3-CF.sub.3--Ph)-5-Pyr
O 34-61 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr--PhO
2-(3-Dma-Ph)-5-Pyr O
[0298]
35TABLE 35 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
35-1 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO Ph O 35-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-Ph--Ph O 35-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 35-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph O 35-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph O 35-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-Pyr O 35-7 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 3-Pyr O 35-8 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-Pyr O 35-9 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-Me-5-Pyr O 35-10 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-Me-3-Pyr O 35-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr O 35-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr O 35-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr O 35-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr O 35-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr O 35-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr O 35-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr O 35-18 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(4-Me--Ph)--Ph O 35-19
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(4-F--Ph)--Ph O 35-20
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(4-Cl--Ph)--Ph O
35-21 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
4-(4-HO-3,5-di-Me--Ph)--Ph O 35-22 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 4-(4-MeO--Ph)--Ph O 35-23 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 4-(4-HO--Ph)--Ph O 35-24 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeO--PhO 4-(4-OHC--Ph)--Ph O 35-25 H (CH.sub.2).sub.2
H Me CH.sub.2 4-MeO--PhO 4-(4-Dma-Ph)--Ph O 35-26 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-MeO--Ph)--Ph O 35-27
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-HO--Ph)--Ph O
35-28 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-Dma-Ph)--Ph
O 35-29 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
4-(2-MeO--Ph)--Ph O 35-30 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 4-(2-HO--Ph)--Ph O 35-31 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 35-32 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeO--PhO 4-(3-EtO-Pyr-6)-Ph O 35-33 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-iPrO-Pyr-6)-Ph O
35-34 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
4-(3-Dma-Pyr-6)-Ph O 35-35 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 4-(3-Dea-Pyr-6)-Ph O 35-36 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 35-37 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
35-38 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr
O 35-39 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
2-(4-Cl--Ph)-5-Pyr O 35-40 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 2-(4-MeO--Ph)-5-Pyr O 35-41 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 2-(4-EtO--Ph)-5-Pyr O 35-42 H (CH.sub.2).sub.2
H Me CH.sub.2 4-MeO--PhO 2-(4-iPrO--Ph)-5-Pyr O 35-43 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-TfpO-5-Pyr O 35-44 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(4-AcO--Ph)--Ph O 35-45
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-F--Ph)--Ph O 35-46
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-Cl--Ph)--Ph O
35-47 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(3-Me--Ph)--Ph
O 35-48 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
4-(3-AcO--Ph)--Ph O 35-49 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 4-(3-Me-Pyr-6)-Ph O 35-50 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 4-(3-Et-Pyr-6)-Ph O 35-51 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeO--PhO 2-(4-Me--Ph)-5-Pyr O 35-52 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-(4-CF.sub.3--Ph)-5-Pyr
O 35-53 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
2-(4-Dma-Ph)-5-Pyr O 35-54 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 2-(3-F--Ph)-5-Pyr O 35-55 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 2-(3-Cl--Ph)-5-Pyr O 35-56 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeO--PhO 2-(3-MeO--Ph)-5-Pyr O 35-57 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-(3-EtO--Ph)-5-Pyr O
35-58 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO
2-(3-iPrO--Ph)-5-Pyr O 35-59 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeO--PhO 2-(3-Me--Ph)-5-Pyr O 35-60 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeO--PhO 2-(3-CF.sub.3--Ph)-5-Pyr O 35-61 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-(3-Dma-Ph)-5-Pyr O
[0299]
36TABLE 36 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
36-1 H (CH.sub.2).sub.2 H Me CH.sub.2 PhS Ph O 36-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-Ph--Ph O 36-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-2)-Ph O 36-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-3)-Ph O 36-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-4)-Ph O 36-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-Pyr O 36-7 H (CH.sub.2).sub.2
H Me CH.sub.2 PhS 3-Pyr O 36-8 H (CH.sub.2).sub.2 H Me CH.sub.2 PhS
4-Pyr O 36-9 H (CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-Me-5-Pyr O
36-10 H (CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-Me-3-Pyr O 36-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-MeO-5-Pyr O 36-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-EtO-5-Pyr O 36-13 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-iPrO-5-Pyr O 36-14 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-MeS-5-Pyr O 36-15 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-EtS-5-Pyr O 36-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-Ph-5-Pyr O 36-17 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 3-Ph-6-Pyr O
[0300]
37TABLE 37 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
37-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 Ph O 37-2
H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph O 37-3
H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph O
37-4 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-3)-Ph O 37-5 H (CH.sub.2).sub.2 H Me CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph O 37-6 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr O 37-7 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr O 37-8 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr O 37-9 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr O 37-10 H (CH.sub.2).sub.2 H
Me CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr O 37-11 H
(CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr O
37-12 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3
2-EtO-5-Pyr O 37-13 H (CH.sub.2).sub.2 H Me CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr O 37-14 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr O 37-15 H (CH.sub.2).sub.2
H Me CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr O 37-16 H
(CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O
37-17 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3
3-Ph-6-Pyr O
[0301]
38TABLE 38 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
38-1 H (CH.sub.2).sub.3 H H CH.sub.2 EtO Ph O 38-2 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-Ph--Ph O 38-3 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-2)-Ph O 38-4 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-3)-Ph O 38-5 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-4)-Ph O 38-6 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Pyr O 38-7 H (CH.sub.2).sub.3 H
H CH.sub.2 EtO 3-Pyr O 38-8 H (CH.sub.2).sub.3 H H CH.sub.2 EtO
4-Pyr O 38-9 H (CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Me-5-Pyr O 38-10
H (CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Me-3-Pyr O 38-11 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-MeO-5-Pyr O 38-12 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-EtO-5-Pyr O 38-13 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-iPrO-5-Pyr O 38-14 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-MeS-5-Pyr O 38-15 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-EtS-5-Pyr O 38-16 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Ph-5-Pyr O 38-17 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 3-Ph-6-Pyr O 38-18 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-Me--Ph)--Ph O 38-19 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-F--Ph)--Ph O 38-20 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-Cl--Ph)--Ph O 38-21 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-HO-3,5-di-Me--Ph)--Ph O
38-22 H (CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-MeO--Ph)--Ph O 38-23
H (CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-HO--Ph)--Ph O 38-24 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-OHC--Ph)--Ph O 38-25 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(4-Dma-Ph)--Ph O 38-26 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-MeO--Ph)--Ph O 38-27 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-HO--Ph)--Ph O 38-28 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-Dma-Ph)--Ph O 38-29 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(2-MeO--Ph)--Ph O 38-30 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(2-HO--Ph)--Ph O 38-31 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 38-32 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-EtO-Pyr-6)-Ph O 38-33 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-iPrO-Pyr-6)-Ph O 38-34 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 38-35 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-Dea-Pyr-6)-Ph O 38-36 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-F.sub.3C-Pyr-6)-Ph O 38-37 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(3-O.sub.2N-Pyr-6)-Ph O 38-38 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O 38-39 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-(4-Cl--Ph)-5-Pyr O 38-40 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O 38-41 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-(4-EtO--Ph)-5-Pyr O 38-42 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-(4-iPrO--Ph)-5-Pyr O 38-43 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-TfpO-5-Pyr O
[0302]
39TABLE 39 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
39-1 H (CH.sub.2).sub.3 H H CH.sub.2 Pr Ph O 39-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-Ph--Ph O 39-3 H (CH.sub.2).sub.3
H H CH.sub.2 Pr 4-(Pyr-2)-Ph O 39-4 H (CH.sub.2).sub.3 H H CH.sub.2
Pr 4-(Pyr-3)-Ph O 39-5 H (CH.sub.2).sub.3 H H CH.sub.2 Pr
4-(Pyr-4)-Ph O 39-6 H (CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Pyr O 39-7
H (CH.sub.2).sub.3 H H CH.sub.2 Pr 3-Pyr O 39-8 H (CH.sub.2).sub.3
H H CH.sub.2 Pr 4-Pyr O 39-9 H (CH.sub.2).sub.3 H H CH.sub.2 Pr
2-Me-5-Pyr O 39-10 H (CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Me-3-Pyr O
39-11 H (CH.sub.2).sub.3 H H CH.sub.2 Pr 2-MeO-5-Pyr O 39-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-EtO-5-Pyr O 39-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-iPrO-5-Pyr O 39-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-MeS-5-Pyr O 39-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-EtS-5-Pyr O 39-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Ph-5-Pyr O 39-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 3-Ph-6-Pyr O 39-18 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-Me--Ph)--Ph O 39-19 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-F--Ph)--Ph O 39-20 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-Cl--Ph)--Ph O 39-21 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-HO-3,5-di-Me--Ph)--Ph O 39-22
H (CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-MeO--Ph)--Ph O 39-23 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-HO--Ph)--Ph O 39-24 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-OHC--Ph)--Ph O 39-25 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(4-Dma-Ph)--Ph O 39-26 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-MeO--Ph)--Ph O 39-27 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-HO--Ph)--Ph O 39-28 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-Dma-Ph)--Ph O 39-29 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(2-MeO--Ph)--Ph O 39-30 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(2-HO--Ph)--Ph O 39-31 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 39-32 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-EtO-Pyr-6)-Ph O 39-33 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-iPrO-Pyr-6)-Ph O 39-34 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 39-35 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-Dea-Pyr-6)-Ph O 39-36 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-F.sub.3C-Pyr-6)-Ph O 39-37 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(3-O.sub.2N-Pyr-6)-Ph O 39-38 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 39-39 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-(4-Cl--Ph)-5-Pyr O 39-40 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 39-41 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-(4-EtO--Ph)-5-Pyr O 39-42 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-(4-iPrO--Ph)-5-Pyr O 39-43 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-TfpO-5-Pyr O
[0303]
40TABLE 40 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
40-1 H (CH.sub.2).sub.3 H H CH.sub.2 Bu Ph O 40-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-Ph--Ph O 40-3 H (CH.sub.2).sub.3
H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 40-4 H (CH.sub.2).sub.3 H H CH.sub.2
Bu 4-(Pyr-3)-Ph O 40-5 H (CH.sub.2).sub.3 H H CH.sub.2 Bu
4-(Pyr-4)-Ph O 40-6 H (CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Pyr O 40-7
H (CH.sub.2).sub.3 H H CH.sub.2 Bu 3-Pyr O 40-8 H (CH.sub.2).sub.3
H H CH.sub.2 Bu 4-Pyr O 40-9 H (CH.sub.2).sub.3 H H CH.sub.2 Bu
2-Me-5-Pyr O 40-10 H (CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Me-3-Pyr O
40-11 H (CH.sub.2).sub.3 H H CH.sub.2 Bu 2-MeO-5-Pyr O 40-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-EtO-5-Pyr O 40-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-iPrO-5-Pyr O 40-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-MeS-5-Pyr O 40-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-EtS-5-Pyr O 40-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Ph-5-Pyr O 40-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 3-Ph-6-Pyr O 40-18 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-Me--Ph)--Ph O 40-19 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-F--Ph)--Ph O 40-20 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-Cl--Ph)--Ph O 40-21 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-HO-3,5-di-Me--Ph)--Ph O 40-22
H (CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-MeO--Ph)--Ph O 40-23 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-HO--Ph)--Ph O 40-24 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-OHC--Ph)--Ph O 40-25 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(4-Dma-Ph)--Ph O 40-26 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-MeO--Ph)--Ph O 40-27 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-HO--Ph)--Ph O 40-28 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-Dma-Ph)--Ph O 40-29 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(2-MeO--Ph)--Ph O 40-30 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(2-HO--Ph)--Ph O 40-31 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 40-32 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-EtO-Pyr-6)-Ph O 40-33 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-iPrO-Pyr-6)-Ph O 40-34 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 40-35 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-Dea-Pyr-6)-Ph O 40-36 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-F.sub.3C-Pyr-6)-Ph O 40-37 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(3-O.sub.2N-Pyr-6)-Ph O 40-38 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 40-39 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-Cl--Ph)-5-Pyr O 40-40 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 40-41 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-EtO--Ph)-5-Pyr O 40-42 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-(4-iPrO--Ph)-5-Pyr O 40-43 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-TfpO-5-Pyr O
[0304]
41TABLE 41 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
41-1 H (CH.sub.2).sub.3 H H CH.sub.2 Pen Ph O 41-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-Ph--Ph O 41-3 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-2)-Ph O 41-4 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-3)-Ph O 41-5 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-4)-Ph O 41-6 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Pyr O 41-7 H (CH.sub.2).sub.3 H
H CH.sub.2 Pen 3-Pyr O 41-8 H (CH.sub.2).sub.3 H H CH.sub.2 Pen
4-Pyr O 41-9 H (CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Me-5-Pyr O 41-10
H (CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Me-3-Pyr O 41-11 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-MeO-5-Pyr O 41-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-EtO-5-Pyr O 41-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-iPrO-5-Pyr O 41-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-MeS-5-Pyr O 41-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-EtS-5-Pyr O 41-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Ph-5-Pyr O 41-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 3-Ph-6-Pyr O
[0305]
42TABLE 42 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
42-1 H (CH.sub.2).sub.3 H H CH.sub.2 MeS Ph O 42-2 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-Ph--Ph O 42-3 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-2)-Ph O 42-4 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-3)-Ph O 42-5 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-4)-Ph O 42-6 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Pyr O 42-7 H (CH.sub.2).sub.3 H
H CH.sub.2 MeS 3-Pyr O 42-8 H (CH.sub.2).sub.3 H H CH.sub.2 MeS
4-Pyr O 42-9 H (CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Me-5-Pyr O 42-10
H (CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Me-3-Pyr O 42-11 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-MeO-5-Pyr O 42-12 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-EtO-5-Pyr O 42-13 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-iPrO-5-Pyr O 42-14 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-MeS-5-Pyr O 42-15 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-EtS-5-Pyr O 42-16 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Ph-5-Pyr O 42-17 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 3-Ph-6-Pyr O
[0306]
43TABLE 43 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
43-1 H (CH.sub.2).sub.3 H H CH.sub.2 PhO Ph O 43-2 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-Ph--Ph O 43-3 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-2)-Ph O 43-4 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-3)-Ph O 43-5 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-4)-Ph O 43-6 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Pyr O 43-7 H (CH.sub.2).sub.3 H
H CH.sub.2 PhO 3-Pyr O 43-8 H (CH.sub.2).sub.3 H H CH.sub.2 PhO
4-Pyr O 43-9 H (CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Me-5-Pyr O 43-10
H (CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Me-3-Pyr O 43-11 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-MeO-5-Pyr O 43-12 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-EtO-5-Pyr O 43-13 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-iPrO-5-Pyr O 43-14 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-MeS-5-Pyr O 43-15 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-EtS-5-Pyr O 43-16 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Ph-5-Pyr O 43-17 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 3-Ph-6-Pyr O 43-18 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-Me--Ph)--Ph O 43-19 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-F--Ph)--Ph O 43-20 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-Cl--Ph)--Ph O 43-21 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-HO-3,5-di-Me--Ph)--Ph O
43-22 H (CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-MeO--Ph)--Ph O 43-23
H (CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-HO--Ph)--Ph O 43-24 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-OHC--Ph)--Ph O 43-25 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(4-Dma-Ph)--Ph O 43-26 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-MeO--Ph)--Ph O 43-27 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-HO--Ph)--Ph O 43-28 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-Dma-Ph)--Ph O 43-29 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(2-MeO--Ph)--Ph O 43-30 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(2-HO--Ph)--Ph O 43-31 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 43-32 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-EtO-Pyr-6)-Ph O 43-33 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-iPrO-Pyr-6)-Ph O 43-34 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 43-35 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-Dea-Pyr-6)-Ph O 43-36 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 43-37 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 43-38 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 43-39 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-(4-Cl--Ph)-5-Pyr O 43-40 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 43-41 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-(4-EtO--Ph)-5-Pyr O 43-42 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-(4-iPrO--Ph)-5-Pyr O 43-43 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-TfpO-5-Pyr O
[0307]
44TABLE 44 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
44-1 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO Ph O 44-2 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 44-3 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 44-4 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph O 44-5 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph O 44-6 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Pyr O 44-7 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 3-Pyr O 44-8 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-Pyr O 44-9 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr O 44-10 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Me-3-Pyr O 44-11 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr O 44-12 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr O 44-13 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr O 44-14 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr O 44-15 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr O 44-16 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr O 44-17 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr O 44-18 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(4-Me--Ph)--Ph O 44-19 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(4-F--Ph)--Ph O 44-20 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(4-Cl--Ph)--Ph O 44-21 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(4-HO-3,5-di-Me--Ph)---
Ph O 44-22 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO
4-(4-MeO--Ph)--Ph O 44-23 H (CH.sub.2).sub.3 H H CH.sub.2
4-iPr--PhO 4-(4-HO--Ph)--Ph O 44-24 H (CH.sub.2).sub.3 H H CH.sub.2
4-iPr--PhO 4-(4-OHC--Ph)--Ph O 44-25 H (CH.sub.2).sub.3 H H
CH.sub.2 4-iPr--PhO 4-(4-Dma-Ph)--Ph O 44-26 H (CH.sub.2).sub.3 H H
CH.sub.2 4-iPr--PhO 4-(3-MeO--Ph)--Ph O 44-27 H (CH.sub.2).sub.3 H
H CH.sub.2 4-iPr--PhO 4-(3-HO--Ph)--Ph O 44-28 H (CH.sub.2).sub.3 H
H CH.sub.2 4-iPr--PhO 4-(3-Dma-Ph)--Ph O 44-29 H (CH.sub.2).sub.3 H
H CH.sub.2 4-iPr--PhO 4-(2-MeO--Ph)--Ph O 44-30 H (CH.sub.2).sub.3
H H CH.sub.2 4-iPr--PhO 4-(2-HO--Ph)--Ph O 44-31 H (CH.sub.2).sub.3
H H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O 44-32 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(3-EtO-Pyr-6)-Ph O 44-33
H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(3-iPrO-Pyr-6)-Ph O
44-34 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(3-Dma-Pyr-6)-Ph
O 44-35 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO
4-(3-Dea-Pyr-6)-Ph O 44-36 H (CH.sub.2).sub.3 H H CH.sub.2
4-iPr--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 44-37 H (CH.sub.2).sub.3 H H
CH.sub.2 4-iPr--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 44-38 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 44-39
H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-(4-Cl--Ph)-5-Pyr O
44-40 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO
2-(4-MeO--Ph)-5-Pyr O 44-41 H (CH.sub.2).sub.3 H H CH.sub.2
4-iPr--PhO 2-(4-EtO--Ph)-5-Pyr O 44-42 H (CH.sub.2).sub.3 H H
CH.sub.2 4-iPr--PhO 2-(4-iPrO--Ph)-5-Pyr O 44-43 H (CH.sub.2).sub.3
H H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O
[0308]
45TABLE 45 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
45-1 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO Ph O 45-2 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 45-3 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 45-4 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph O 45-5 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph O 45-6 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Pyr O 45-7 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 3-Pyr O 45-8 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-Pyr O 45-9 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pyr O 45-10 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Me-3-Pyr O 45-11 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr O 45-12 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr O 45-13 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr O 45-14 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr O 45-15 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr O 45-16 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr O 45-17 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr O 45-18 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(4-Me--Ph)--Ph O 45-19 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(4-F--Ph)--Ph O 45-20 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(4-Cl--Ph)--Ph O 45-21 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(4-HO-3,5-di-Me--Ph)---
Ph O 45-22 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO
4-(4-MeO--Ph)--Ph O 45-23 H (CH.sub.2).sub.3 H H CH.sub.2
4-MeO--PhO 4-(4-HO--Ph)--Ph O 45-24 H (CH.sub.2).sub.3 H H CH.sub.2
4-MeO--PhO 4-(4-OHC--Ph)--Ph O 45-25 H (CH.sub.2).sub.3 H H
CH.sub.2 4-MeO--PhO 4-(4-Dma-Ph)--Ph O 45-26 H (CH.sub.2).sub.3 H H
CH.sub.2 4-MeO--PhO 4-(3-MeO--Ph)--Ph O 45-27 H (CH.sub.2).sub.3 H
H CH.sub.2 4-MeO--PhO 4-(3-HO--Ph)--Ph O 45-28 H (CH.sub.2).sub.3 H
H CH.sub.2 4-MeO--PhO 4-(3-Dma-Ph)--Ph O 45-29 H (CH.sub.2).sub.3 H
H CH.sub.2 4-MeO--PhO 4-(2-MeO--Ph)--Ph O 45-30 H (CH.sub.2).sub.3
H H CH.sub.2 4-MeO--PhO 4-(2-HO--Ph)--Ph O 45-31 H (CH.sub.2).sub.3
H H CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 45-32 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(3-EtO-Pyr-6)-Ph O 45-33
H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(3-iPrO-Pyr-6)-Ph O
45-34 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph
O 45-35 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO
4-(3-Dea-Pyr-6)-Ph O 45-36 H (CH.sub.2).sub.3 H H CH.sub.2
4-MeO--PhO 4-(3-F.sub.3C-Pyr-6)-Ph O 45-37 H (CH.sub.2).sub.3 H H
CH.sub.2 4-MeO--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 45-38 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O 45-39
H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-(4-Cl--Ph)-5-Pyr O
45-40 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO
2-(4-MeO--Ph)-5-Pyr O 45-41 H (CH.sub.2).sub.3 H H CH.sub.2
4-MeO--PhO 2-(4-EtO--Ph)-5-Pyr O 45-42 H (CH.sub.2).sub.3 H H
CH.sub.2 4-MeO--PhO 2-(4-iPrO--Ph)-5-Pyr O 45-43 H (CH.sub.2).sub.3
H H CH.sub.2 4-MeO--PhO 2-TfpO-5-Pyr O
[0309]
46TABLE 46 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
46-1 H (CH.sub.2).sub.3 H H CH.sub.2 PhS Ph O 46-2 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-Ph--Ph O 46-3 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-2)-Ph O 46-4 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-3)-Ph O 46-5 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-4)-Ph O 46-6 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Pyr O 46-7 H (CH.sub.2).sub.3 H
H CH.sub.2 PhS 3-Pyr O 46-8 H (CH.sub.2).sub.3 H H CH.sub.2 PhS
4-Pyr O 46-9 H (CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Me-5-Pyr O 46-10
H (CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Me-3-Pyr O 46-11 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-MeO-5-Pyr O 46-12 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-EtO-5-Pyr O 46-13 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-iPrO-5-Pyr O 46-14 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-MeS-5-Pyr O 46-15 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-EtS-5-Pyr O 46-16 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Ph-5-Pyr O 46-17 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 3-Ph-6-Pyr O
[0310]
47TABLE 47 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
47-1 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph O 47-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph O 47-3 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph O
47-4 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-3)-Ph O 47-5 H (CH.sub.2).sub.3 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph O 47-6 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr O 47-7 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr O 47-8 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr O 47-9 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr O 47-10 H (CH.sub.2).sub.3 H
H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr O 47-11 H (CH.sub.2).sub.3
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr O 47-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtO-5-Pyr O
47-13 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-iPrO-5-Pyr O 47-14 H (CH.sub.2).sub.3 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-MeS-5-Pyr O 47-15 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr O 47-16 H (CH.sub.2).sub.3
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O 47-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr O
[0311]
48TABLE 48 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
48-1 H CHMeCH.sub.2 H H CH.sub.2 EtO Ph O 48-2 H CHMeCH.sub.2 H H
CH.sub.2 EtO 4-Ph--Ph O 48-3 H CHMeCH.sub.2 H H CH.sub.2 EtO
4-(Pyr-2)-Ph O 48-4 H CHMeCH.sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph O
48-5 H CHMeCH.sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph O 48-6 H
CHMeCH.sub.2 H H CH.sub.2 EtO 2-Pyr O 48-7 H CHMeCH.sub.2 H H
CH.sub.2 EtO 3-Pyr O 48-8 H CHMeCH.sub.2 H H CH.sub.2 EtO 4-Pyr O
48-9 H CHMeCH.sub.2 H H CH.sub.2 EtO 2-Me-5-Pyr O 48-10 H
CHMeCH.sub.2 H H CH.sub.2 EtO 2-Me-3-Pyr O 48-11 H CHMeCH.sub.2 H H
CH.sub.2 EtO 2-MeO-5-Pyr O 48-12 H CHMeCH.sub.2 H H CH.sub.2 EtO
2-EtO-5-Pyr O 48-13 H CHMeCH.sub.2 H H CH.sub.2 EtO 2-iPrO-5-Pyr O
48-14 H CHMeCH.sub.2 H H CH.sub.2 EtO 2-MeS-5-Pyr O 48-15 H
CHMeCH.sub.2 H H CH.sub.2 EtO 2-EtS-5-Pyr O 48-16 H CHMeCH.sub.2 H
H CH.sub.2 EtO 2-Ph-5-Pyr O 48-17 H CHMeCH.sub.2 H H CH.sub.2 EtO
3-Ph-6-Pyr O
[0312]
49TABLE 49 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
49-1 H CHMeCH.sub.2 H H CH.sub.2 Pr Ph O 49-2 H CHMeCH.sub.2 H H
CH.sub.2 Pr 4-Ph--Ph O 49-3 H CHMeCH.sub.2 H H CH.sub.2 Pr
4-(Pyr-2)-Ph O 49-4 H CHMeCH.sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph O
49-5 H CHMeCH.sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph O 49-6 H
CHMeCH.sub.2 H H CH.sub.2 Pr 2-Pyr O 49-7 H CHMeCH.sub.2 H H
CH.sub.2 Pr 3-Pyr O 49-8 H CHMeCH.sub.2 H H CH.sub.2 Pr 4-Pyr O
49-9 H CHMeCH.sub.2 H H CH.sub.2 Pr 2-Me-5-Pyr O 49-10 H
CHMeCH.sub.2 H H CH.sub.2 Pr 2-Me-3-Pyr O 49-11 H CHMeCH.sub.2 H H
CH.sub.2 Pr 2-MeO-5-Pyr O 49-12 H CHMeCH.sub.2 H H CH.sub.2 Pr
2-EtO-5-Pyr O 49-13 H CHMeCH.sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pyr O
49-14 H CHMeCH.sub.2 H H CH.sub.2 Pr 2-MeS-5-Pyr O 49-15 H
CHMeCH.sub.2 H H CH.sub.2 Pr 2-EtS-5-Pyr O 49-16 H CHMeCH.sub.2 H H
CH.sub.2 Pr 2-Ph-5-Pyr O 49-17 H CHMeCH.sub.2 H H CH.sub.2 Pr
3-Ph-6-Pyr O
[0313]
50TABLE 50 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
50-1 H CHMeCH.sub.2 H H CH.sub.2 Bu Ph O 50-2 H CHMeCH.sub.2 H H
CH.sub.2 Bu 4-Ph--Ph O 50-3 H CHMeCH.sub.2 H H CH.sub.2 Bu
4-(Pyr-2)-Ph O 50-4 H CHMeCH.sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O
50-5 H CHMeCH.sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 50-6 H
CHMeCH.sub.2 H H CH.sub.2 Bu 2-Pyr O 50-7 H CHMeCH.sub.2 H H
CH.sub.2 Bu 3-Pyr O 50-8 H CHMeCH.sub.2 H H CH.sub.2 Bu 4-Pyr O
50-9 H CHMeCH.sub.2 H H CH.sub.2 Bu 2-Me-5-Pyr O 50-10 H
CHMeCH.sub.2 H H CH.sub.2 Bu 2-Me-3-Pyr O 50-11 H CHMeCH.sub.2 H H
CH.sub.2 Bu 2-MeO-5-Pyr O 50-12 H CHMeCH.sub.2 H H CH.sub.2 Bu
2-EtO-5-Pyr O 50-13 H CHMeCH.sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pyr O
50-14 H CHMeCH.sub.2 H H CH.sub.2 Bu 2-MeS-5-Pyr O 50-15 H
CHMeCH.sub.2 H H CH.sub.2 Bu 2-EtS-5-Pyr O 50-16 H CHMeCH.sub.2 H H
CH.sub.2 Bu 2-Ph-5-Pyr O 50-17 H CHMeCH.sub.2 H H CH.sub.2 Bu
3-Ph-6-Pyr O
[0314]
51TABLE 51 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
51-1 H CHMeCH.sub.2 H H CH.sub.2 Pen Ph O 51-2 H CHMeCH.sub.2 H H
CH.sub.2 Pen 4-Ph--Ph O 51-3 H CHMeCH.sub.2 H H CH.sub.2 Pen
4-(Pyr-2)-Ph O 51-4 H CHMeCH.sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph O
51-5 H CHMeCH.sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph O 51-6 H
CHMeCH.sub.2 H H CH.sub.2 Pen 2-Pyr O 51-7 H CHMeCH.sub.2 H H
CH.sub.2 Pen 3-Pyr O 51-8 H CHMeCH.sub.2 H H CH.sub.2 Pen 4-Pyr O
51-9 H CHMeCH.sub.2 H H CH.sub.2 Pen 2-Me-5-Pyr O 51-10 H
CHMeCH.sub.2 H H CH.sub.2 Pen 2-Me-3-Pyr O 51-11 H CHMeCH.sub.2 H H
CH.sub.2 Pen 2-MeO-5-Pyr O 51-12 H CHMeCH.sub.2 H H CH.sub.2 Pen
2-EtO-5-Pyr O 51-13 H CHMeCH.sub.2 H H CH.sub.2 Pen 2-iPrO-5-Pyr O
51-14 H CHMeCH.sub.2 H H CH.sub.2 Pen 2-MeS-5-Pyr O 51-15 H
CHMeCH.sub.2 H H CH.sub.2 Pen 2-EtS-5-Pyr O 51-16 H CHMeCH.sub.2 H
H CH.sub.2 Pen 2-Ph-5-Pyr O 51-17 H CHMeCH.sub.2 H H CH.sub.2 Pen
3-Ph-6-Pyr O
[0315]
52TABLE 52 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
52-1 H CHMeCH.sub.2 H H CH.sub.2 MeS Ph O 52-2 H CHMeCH.sub.2 H H
CH.sub.2 MeS 4-Ph--Ph O 52-3 H CHMeCH.sub.2 H H CH.sub.2 MeS
4-(Pyr-2)-Ph O 52-4 H CHMeCH.sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph O
52-5 H CHMeCH.sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph O 52-6 H
CHMeCH.sub.2 H H CH.sub.2 MeS 2-Pyr O 52-7 H CHMeCH.sub.2 H H
CH.sub.2 MeS 3-Pyr O 52-8 H CHMeCH.sub.2 H H CH.sub.2 MeS 4-Pyr O
52-9 H CHMeCH.sub.2 H H CH.sub.2 MeS 2-Me-5-Pyr O 52-10 H
CHMeCH.sub.2 H H CH.sub.2 MeS 2-Me-3-Pyr O 52-11 H CHMeCH.sub.2 H H
CH.sub.2 MeS 2-MeO-5-Pyr O 52-12 H CHMeCH.sub.2 H H CH.sub.2 MeS
2-EtO-5-Pyr O 52-13 H CHMeCH.sub.2 H H CH.sub.2 MeS 2-iPrO-5-Pyr O
52-14 H CHMeCH.sub.2 H H CH.sub.2 MeS 2-MeS-5-Pyr O 52-15 H
CHMeCH.sub.2 H H CH.sub.2 MeS 2-EtS-5-Pyr O 52-16 H CHMeCH.sub.2 H
H CH.sub.2 MeS 2-Ph-5-Pyr O 52-17 H CHMeCH.sub.2 H H CH.sub.2 MeS
3-Ph-6-Pyr O
[0316]
53TABLE 53 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
53-1 H CHMeCH.sub.2 H H CH.sub.2 PhO Ph O 53-2 H CHMeCH.sub.2 H H
CH.sub.2 PhO 4-Ph--Ph O 53-3 H CHMeCH.sub.2 H H CH.sub.2 PhO
4-(Pyr-2)-Ph O 53-4 H CHMeCH.sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph O
53-5 H CHMeCH.sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph O 53-6 H
CHMeCH.sub.2 H H CH.sub.2 PhO 2-Pyr O 53-7 H CHMeCH.sub.2 H H
CH.sub.2 PhO 3-Pyr O 53-8 H CHMeCH.sub.2 H H CH.sub.2 PhO 4-Pyr O
53-9 H CHMeCH.sub.2 H H CH.sub.2 PhO 2-Me-5-Pyr O 53-10 H
CHMeCH.sub.2 H H CH.sub.2 PhO 2-Me-3-Pyr O 53-11 H CHMeCH.sub.2 H H
CH.sub.2 PhO 2-MeO-5-Pyr O 53-12 H CHMeCH.sub.2 H H CH.sub.2 PhO
2-EtO-5-Pyr O 53-13 H CHMeCH.sub.2 H H CH.sub.2 PhO 2-iPrO-5-Pyr O
53-14 H CHMeCH.sub.2 H H CH.sub.2 PhO 2-MeS-5-Pyr O 53-15 H
CHMeCH.sub.2 H H CH.sub.2 PhO 2-EtS-5-Pyr O 53-16 H CHMeCH.sub.2 H
H CH.sub.2 PhO 2-Ph-5-Pyr O 53-17 H CHMeCH.sub.2 H H CH.sub.2 PhO
3-Ph-6-Pyr O
[0317]
54TABLE 54 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
54-1 H CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO Ph O 54-2 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 54-3 H CHMeCH.sub.2
H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 54-4 H CHMeCH.sub.2 H H
CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph O 54-5 H CHMeCH.sub.2 H H CH.sub.2
4-iPr--PhO 4-(Pyr-4)-Ph O 54-6 H CHMeCH.sub.2 H H CH.sub.2
4-iPr--PhO 2-Pyr O 54-7 H CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO
3-Pyr O 54-8 H CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 4-Pyr O 54-9 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr O 54-10 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-3-Pyr O 54-11 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr O 54-12 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr O 54-13 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr O 54-14 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr O 54-15 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr O 54-16 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr O 54-17 H
CHMeCH.sub.2 H H CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr O
[0318]
55TABLE 55 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
55-1 H CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO Ph O 55-2 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 55-3 H CHMeCH.sub.2
H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 55-4 H CHMeCH.sub.2 H H
CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph O 55-5 H CHMeCH.sub.2 H H CH.sub.2
4-MeO--PhO 4-(Pyr-4)-Ph O 55-6 H CHMeCH.sub.2 H H CH.sub.2
4-MeO--PhO 2-Pyr O 55-7 H CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO
3-Pyr O 55-8 H CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 4-Pyr O 55-9 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pyr O 55-10 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-Me-3-Pyr O 55-11 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr O 55-12 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr O 55-13 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr O 55-14 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr O 55-15 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr O 55-16 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr O 55-17 H
CHMeCH.sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr O
[0319]
56TABLE 56 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
56-1 H CHMeCH.sub.2 H H CH.sub.2 PhS Ph O 56-2 H CHMeCH.sub.2 H H
CH.sub.2 PhS 4-Ph--Ph O 56-3 H CHMeCH.sub.2 H H CH.sub.2 PhS
4-(Pyr-2)-Ph O 56-4 H CHMeCH.sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph O
56-5 H CHMeCH.sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph O 56-6 H
CHMeCH.sub.2 H H CH.sub.2 PhS 2-Pyr O 56-7 H CHMeCH.sub.2 H H
CH.sub.2 PhS 3-Pyr O 56-8 H CHMeCH.sub.2 H H CH.sub.2 PhS 4-Pyr O
56-9 H CHMeCH.sub.2 H H CH.sub.2 PhS 2-Me-5-Pyr O 56-10 H
CHMeCH.sub.2 H H CH.sub.2 PhS 2-Me-3-Pyr O 56-11 H CHMeCH.sub.2 H H
CH.sub.2 PhS 2-MeO-5-Pyr O 56-12 H CHMeCH.sub.2 H H CH.sub.2 PhS
2-EtO-5-Pyr O 56-13 H CHMeCH.sub.2 H H CH.sub.2 PhS 2-iPrO-5-Pyr O
56-14 H CHMeCH.sub.2 H H CH.sub.2 PhS 2-MeS-5-Pyr O 56-15 H
CHMeCH.sub.2 H H CH.sub.2 PhS 2-EtS-5-Pyr O 56-16 H CHMeCH.sub.2 H
H CH.sub.2 PhS 2-Ph-5-Pyr O 56-17 H CHMeCH.sub.2 H H CH.sub.2 PhS
3-Ph-6-Pyr O
[0320]
57TABLE 57 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
57-1 H CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph O 57-2 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph O 57-3 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph O 57-4 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph O 57-5 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph O 57-6 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr O 57-7 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr O 57-8 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr O 57-9 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr O 57-10 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr O 57-11 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr O 57-12 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtO-5-Pyr O 57-13 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr O 57-14 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr O 57-15 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr O 57-16 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O 57-17 H
CHMeCH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr O
[0321]
58TABLE 58 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
58-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO Ph -- 58-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph -- 58-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph -- 58-4 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph -- 58-5 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph -- 58-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Pyr -- 58-7 H (CH.sub.2).sub.2
H H CH.sub.2 EtO 3-Pyr -- 58-8 H (CH.sub.2).sub.2 H H CH.sub.2 EtO
4-Pyr -- 58-9 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-5-Pyr --
58-10 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Me-3-Pyr -- 58-11 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeO-5-Pyr -- 58-12 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtO-5-Pyr -- 58-13 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-iPrO-5-Pyr -- 58-14 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-MeS-5-Pyr -- 58-15 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-EtS-5-Pyr -- 58-16 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr -- 58-17 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr --
[0322]
59TABLE 59 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
59-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pr Ph -- 59-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph--Ph -- 59-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph -- 59-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph -- 59-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph -- 59-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Pyr -- 59-7 H (CH.sub.2).sub.2 H
H CH.sub.2 Pr 3-Pyr -- 59-8 H (CH.sub.2).sub.2 H H CH.sub.2 Pr
4-Pyr -- 59-9 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-5-Pyr --
59-10 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Me-3-Pyr -- 59-11 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeO-5-Pyr -- 59-12 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtO-5-Pyr -- 59-13 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pyr -- 59-14 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-MeS-5-Pyr -- 59-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-EtS-5-Pyr -- 59-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr -- 59-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr --
[0323]
60TABLE 60 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
60-1 H (CH.sub.2).sub.2 H H CH.sub.2 Bu Ph -- 60-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph-Ph -- 60-3 H (CH.sub.2).sub.2
H H CH.sub.2 Bu 4-(Pyr-2)-Ph -- 60-4 H (CH.sub.2).sub.2 H H
CH.sub.2 Bu 4-(Pyr-3)-Ph -- 60-5 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
4-(Pyr-4)-Ph -- 60-6 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Pyr --
60-7 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Pyr -- 60-8 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Pyr -- 60-9 H (CH.sub.2).sub.2 H
H CH.sub.2 Bu 2-Me-5-Pyr -- 60-10 H (CH.sub.2).sub.2 H H CH.sub.2
Bu 2-Me-3-Pyr -- 60-11 H (CH.sub.2).sub.2 H H CH.sub.2 Bu
2-MeO-5-Pyr -- 60-12 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtO-5-Pyr
-- 60-13 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pyr -- 60-14 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-MeS-5-Pyr -- 60-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-EtS-5-Pyr -- 60-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr -- 60-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr --
[0324]
61TABLE 61 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
61-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pen Ph -- 61-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph -- 61-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph -- 61-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph -- 61-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph -- 61-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Pyr -- 61-7 H (CH.sub.2).sub.2
H H CH.sub.2 Pen 3-Pyr -- 61-8 H (CH.sub.2).sub.2 H H CH.sub.2 Pen
4-Pyr -- 61-9 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-5-Pyr --
61-10 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Me-3-Pyr -- 61-11 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeO-5-Pyr -- 61-12 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtO-5-Pyr -- 61-13 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-iPrO-5-Pyr -- 61-14 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-MeS-5-Pyr -- 61-15 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-EtS-5-Pyr -- 61-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr -- 61-17 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr --
[0325]
62TABLE 62 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
62-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS Ph -- 62-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph--Ph -- 62-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph -- 62-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph -- 62-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph -- 62-6 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Pyr -- 62-7 H (CH.sub.2).sub.2
H H CH.sub.2 MeS 3-Pyr -- 62-8 H (CH.sub.2).sub.2 H H CH.sub.2 MeS
4-Pyr -- 62-9 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Me-5-Pyr --
62-10 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Me-3-Pyr -- 62-11 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeO-5-Pyr -- 62-12 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtO-5-Pyr -- 62-13 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-iPrO-5-Pyr -- 62-14 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-MeS-5-Pyr -- 62-15 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-EtS-5-Pyr -- 62-16 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr -- 62-17 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr --
[0326]
63TABLE 63 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
63-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhO Ph -- 63-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph--Ph -- 63-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph -- 63-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph -- 63-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph -- 63-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Pyr -- 63-7 H (CH.sub.2).sub.2
H H CH.sub.2 PhO 3-Pyr -- 63-8 H (CH.sub.2).sub.2 H H CH.sub.2 PhO
4-Pyr -- 63-9 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-5-Pyr --
63-10 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Me-3-Pyr -- 63-11 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeO-5-Pyr -- 63-12 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtO-5-Pyr -- 63-13 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-iPrO-5-Pyr -- 63-14 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-MeS-5-Pyr -- 63-15 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-EtS-5-Pyr -- 63-16 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr -- 63-17 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr --
[0327]
64TABLE 64 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
64-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO Ph -- 64-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph -- 64-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph -- 64-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph -- 64-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph -- 64-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Pyr -- 64-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Pyr -- 64-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 4-Pyr -- 64-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr -- 64-10 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Me-3-Pyr -- 64-11 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr -- 64-12 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr -- 64-13 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr -- 64-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr -- 64-15 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr -- 64-16 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr -- 64-17 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr --
[0328]
65TABLE 65 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
65-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO- Ph -- PhO 65-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 4-Ph-Ph -- PhO 65-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 4-(Pyr-2)-Ph -- PhO 65-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 4-(Pyr-3)-Ph -- PhO 65-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 4-(Pyr-4)-Ph -- PhO 65-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-Pyr -- PhO 65-7 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 3-Pyr -- PhO 65-8 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 4-Pyr -- PhO 65-9 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-Me-5-Pyr -- PhO 65-10 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-Me-3-Pyr -- PhO 65-11 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-MeO-5-Pyr -- PhO 65-12 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-EtO-5-Pyr -- PhO 65-13 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-iPrO-5-Pyr -- PhO 65-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-MeS-5-Pyr -- PhO 65-15 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-EtS-5-Pyr -- PhO 65-16 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 2-Ph-5-Pyr -- PhO 65-17 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO- 3-Ph-6-Pyr -- PhO
[0329]
66TABLE 66 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
66-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS Ph -- 66-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph--Ph -- 66-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph -- 66-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph -- 66-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph -- 66-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Pyr -- 66-7 H (CH.sub.2).sub.2
H H CH.sub.2 PhS 3-Pyr -- 66-8 H (CH.sub.2).sub.2 H H CH.sub.2 PhS
4-Pyr -- 66-9 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Me-5-Pyr --
66-10 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Me-3-Pyr -- 66-11 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeO-5-Pyr -- 66-12 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtO-5-Pyr -- 66-13 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-iPrO-5-Pyr -- 66-14 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-MeS-5-Pyr -- 66-15 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-EtS-5-Pyr -- 66-16 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr -- 66-17 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr --
[0330]
67TABLE 67 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
67-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph -- 67-2
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph -- 67-3
H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph --
67-4 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-3)-Ph -- 67-5 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph -- 67-6 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr -- 67-7 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr -- 67-8 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr -- 67-9 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr -- 67-10 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr -- 67-11 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr --
67-12 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtO-5-Pyr -- 67-13 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr -- 67-14 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr -- 67-15 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr -- 67-16 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr --
67-17 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr
--
[0331]
68TABLE 68 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
68-1 H (CH.sub.2).sub.3 H H CH.sub.2 EtO Ph -- 68-2 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-Ph--Ph -- 68-3 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-2)-Ph -- 68-4 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-3)-Ph -- 68-5 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 4-(Pyr-4)-Ph -- 68-6 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Pyr -- 68-7 H (CH.sub.2).sub.3
H H CH.sub.2 EtO 3-Pyr -- 68-8 H (CH.sub.2).sub.3 H H CH.sub.2 EtO
4-Pyr -- 68-9 H (CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Me-5-Pyr --
68-10 H (CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Me-3-Pyr -- 68-11 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-MeO-5-Pyr -- 68-12 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-EtO-5-Pyr -- 68-13 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-iPrO-5-Pyr -- 68-14 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-MeS-5-Pyr -- 68-15 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-EtS-5-Pyr -- 68-16 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 2-Ph-5-Pyr -- 68-17 H
(CH.sub.2).sub.3 H H CH.sub.2 EtO 3-Ph-6-Pyr --
[0332]
69TABLE 69 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
69-1 H (CH.sub.2).sub.3 H H CH.sub.2 Pr Ph -- 69-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-Ph--Ph -- 69-3 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(Pyr-2)-Ph -- 69-4 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(Pyr-3)-Ph -- 69-5 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 4-(Pyr-4)-Ph -- 69-6 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Pyr -- 69-7 H (CH.sub.2).sub.3 H
H CH.sub.2 Pr 3-Pyr -- 69-8 H (CH.sub.2).sub.3 H H CH.sub.2 Pr
4-Pyr -- 69-9 H (CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Me-5-Pyr --
69-10 H (CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Me-3-Pyr -- 69-11 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-MeO-5-Pyr -- 69-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-EtO-5-Pyr -- 69-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-iPrO-5-Pyr -- 69-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-MeS-5-Pyr -- 69-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-EtS-5-Pyr -- 69-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 2-Ph-5-Pyr -- 69-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Pr 3-Ph-6-Pyr --
[0333]
70TABLE 70 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
70-1 H (CH.sub.2).sub.3 H H CH.sub.2 Bu Ph -- 70-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-Ph--Ph -- 70-3 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-2)-Ph -- 70-4 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-3)-Ph -- 70-5 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 4-(Pyr-4)-Ph -- 70-6 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Pyr -- 70-7 H (CH.sub.2).sub.3 H
H CH.sub.2 Bu 3-Pyr -- 70-8 H (CH.sub.2).sub.3 H H CH.sub.2 Bu
4-Pyr -- 70-9 H (CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Me-5-Pyr --
70-10 H (CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Me-3-Pyr -- 70-11 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-MeO-5-Pyr -- 70-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-EtO-5-Pyr -- 70-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-iPrO-5-Pyr -- 70-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-MeS-5-Pyr -- 70-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-EtS-5-Pyr -- 70-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 2-Ph-5-Pyr -- 70-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Bu 3-Ph-6-Pyr --
[0334]
71TABLE 71 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
71-1 H (CH.sub.2).sub.3 H H CH.sub.2 Pen Ph -- 71-2 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-Ph--Ph -- 71-3 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-2)-Ph -- 71-4 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-3)-Ph -- 71-5 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 4-(Pyr-4)-Ph -- 71-6 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Pyr -- 71-7 H (CH.sub.2).sub.3
H H CH.sub.2 Pen 3-Pyr -- 71-8 H (CH.sub.2).sub.3 H H CH.sub.2 Pen
4-Pyr -- 71-9 H (CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Me-5-Pyr --
71-10 H (CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Me-3-Pyr -- 71-11 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-MeO-5-Pyr -- 71-12 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-EtO-5-Pyr -- 71-13 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-iPrO-5-Pyr -- 71-14 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-MeS-5-Pyr -- 71-15 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-EtS-5-Pyr -- 71-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 2-Ph-5-Pyr -- 71-17 H
(CH.sub.2).sub.3 H H CH.sub.2 Pen 3-Ph-6-Pyr --
[0335]
72TABLE 72 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
72-1 H (CH.sub.2).sub.3 H H CH.sub.2 MeS Ph -- 72-2 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-Ph--Ph -- 72-3 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-2)-Ph -- 72-4 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-3)-Ph -- 72-5 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 4-(Pyr-4)-Ph -- 72-6 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Pyr -- 72-7 H (CH.sub.2).sub.3
H H CH.sub.2 MeS 3-Pyr -- 72-8 H (CH.sub.2).sub.3 H H CH.sub.2 MeS
4-Pyr -- 72-9 H (CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Me-5-Pyr --
72-10 H (CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Me-3-Pyr -- 72-11 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-MeO-5-Pyr -- 72-12 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-EtO-5-Pyr -- 72-13 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-iPrO-5-Pyr -- 72-14 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-MeS-5-Pyr -- 72-15 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-EtS-5-Pyr -- 72-16 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 2-Ph-5-Pyr -- 72-17 H
(CH.sub.2).sub.3 H H CH.sub.2 MeS 3-Ph-6-Pyr --
[0336]
73TABLE 73 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
73-1 H (CH.sub.2).sub.3 H H CH.sub.2 PhO Ph -- 73-2 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-Ph--Ph -- 73-3 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-2)-Ph -- 73-4 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-3)-Ph -- 73-5 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 4-(Pyr-4)-Ph -- 73-6 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Pyr -- 73-7 H (CH.sub.2).sub.3
H H CH.sub.2 PhO 3-Pyr -- 73-8 H (CH.sub.2).sub.3 H H CH.sub.2 PhO
4-Pyr -- 73-9 H (CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Me-5-Pyr --
73-10 H (CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Me-3-Pyr -- 73-11 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-MeO-5-Pyr -- 73-12 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-EtO-5-Pyr -- 73-13 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-iPrO-5-Pyr -- 73-14 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-MeS-5-Pyr -- 73-15 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-EtS-5-Pyr -- 73-16 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 2-Ph-5-Pyr -- 73-17 H
(CH.sub.2).sub.3 H H CH.sub.2 PhO 3-Ph-6-Pyr --
[0337]
74TABLE 74 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
74-1 H (CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO Ph -- 74-2 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-Ph--Ph -- 74-3 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph -- 74-4 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph -- 74-5 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph -- 74-6 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Pyr -- 74-7 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 3-Pyr -- 74-8 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 4-Pyr -- 74-9 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Me-5-Pyr -- 74-10 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Me-3-Pyr -- 74-11 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-MeO-5-Pyr -- 74-12 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-EtO-5-Pyr -- 74-13 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-iPrO-5-Pyr -- 74-14 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-MeS-5-Pyr -- 74-15 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-EtS-5-Pyr -- 74-16 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 2-Ph-5-Pyr -- 74-17 H
(CH.sub.2).sub.3 H H CH.sub.2 4-iPr--PhO 3-Ph-6-Pyr --
[0338]
75TABLE 75 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
75-1 H (CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO Ph -- 75-2 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph -- 75-3 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph -- 75-4 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph -- 75-5 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph -- 75-6 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Pyr -- 75-7 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 3-Pyr -- 75-8 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 4-Pyr -- 75-9 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Me-5-Pyr -- 75-10 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Me-3-Pyr -- 75-11 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr -- 75-12 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr -- 75-13 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr -- 75-14 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr -- 75-15 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-EtS-5-Pyr -- 75-16 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 2-Ph-5-Pyr -- 75-17 H
(CH.sub.2).sub.3 H H CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr --
[0339]
76TABLE 76 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
76-1 H (CH.sub.2).sub.3 H H CH.sub.2 PhS Ph -- 76-2 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-Ph--Ph -- 76-3 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-2)-Ph -- 76-4 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-3)-Ph -- 76-5 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 4-(Pyr-4)-Ph -- 76-6 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Pyr -- 76-7 H (CH.sub.2).sub.3
H H CH.sub.2 PhS 3-Pyr -- 76-8 H (CH.sub.2).sub.3 H H CH.sub.2 PhS
4-Pyr -- 76-9 H (CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Me-5-Pyr --
76-10 H (CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Me-3-Pyr -- 76-11 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-MeO-5-Pyr -- 76-12 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-EtO-5-Pyr -- 76-13 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-iPrO-5-Pyr -- 76-14 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-MeS-5-Pyr -- 76-15 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-EtS-5-Pyr -- 76-16 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 2-Ph-5-Pyr -- 76-17 H
(CH.sub.2).sub.3 H H CH.sub.2 PhS 3-Ph-6-Pyr --
[0340]
77TABLE 77 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
77-1 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph -- 77-2
H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph -- 77-3
H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph --
77-4 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-3)-Ph -- 77-5 H (CH.sub.2).sub.3 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph -- 77-6 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr -- 77-7 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr -- 77-8 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-Pyr -- 77-9 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-5-Pyr -- 77-10 H (CH.sub.2).sub.3
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Me-3-Pyr -- 77-11 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-MeO-5-Pyr --
77-12 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3
2-EtO-5-Pyr -- 77-13 H (CH.sub.2).sub.3 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr -- 77-14 H (CH.sub.2).sub.3 H H
CH.sub.2 Ph(CH.sub.2).sub.3 2-MeS-5-Pyr -- 77-15 H (CH.sub.2).sub.3
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-EtS-5-Pyr -- 77-16 H
(CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr --
77-17 H (CH.sub.2).sub.3 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr
--
[0341]
78TABLE 78 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
78-1 H CH.sub.2 H H CH.sub.2 EtO Ph -- 78-2 H CH.sub.2 H H CH.sub.2
EtO 4-Ph--Ph -- 78-3 H CH.sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph --
78-4 H CH.sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph -- 78-5 H CH.sub.2 H
H CH.sub.2 EtO 4-(Pyr-4)-Ph -- 78-6 H CH.sub.2 H H CH.sub.2 EtO
2-Pyr -- 78-7 H CH.sub.2 H H CH.sub.2 EtO 3-Pyr -- 78-8 H CH.sub.2
H H CH.sub.2 EtO 4-Pyr -- 78-9 H CH.sub.2 H H CH.sub.2 EtO
2-Me-5-Pyr -- 78-10 H CH.sub.2 H H CH.sub.2 EtO 2-Me-3-Pyr -- 78-11
H CH.sub.2 H H CH.sub.2 EtO 2-MeO-5-Pyr -- 78-12 H CH.sub.2 H H
CH.sub.2 EtO 2-EtO-5-Pyr -- 78-13 H CH.sub.2 H H CH.sub.2 EtO
2-iPrO-5-Pyr -- 78-14 H CH.sub.2 H H CH.sub.2 EtO 2-MeS-5-Pyr --
78-15 H CH.sub.2 H H CH.sub.2 EtO 2-EtS-5-Pyr -- 78-16 H CH.sub.2 H
H CH.sub.2 EtO 2-Ph-5-Pyr -- 78-17 H CH.sub.2 H H CH.sub.2 EtO
3-Ph-6-Pyr --
[0342]
79TABLE 79 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
79-1 H CH.sub.2 H H CH.sub.2 Pr Ph -- 79-2 H CH.sub.2 H H CH.sub.2
Pr 4-Ph--Ph -- 79-3 H CH.sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph -- 79-4
H CH.sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph -- 79-5 H CH.sub.2 H H
CH.sub.2 Pr 4-(Pyr-4)-Ph -- 79-6 H CH.sub.2 H H CH.sub.2 Pr 2-Pyr
-- 79-7 H CH.sub.2 H H CH.sub.2 Pr 3-Pyr -- 79-8 H CH.sub.2 H H
CH.sub.2 Pr 4-Pyr -- 79-9 H CH.sub.2 H H CH.sub.2 Pr 2-Me-5-Pyr --
79-10 H CH.sub.2 H H CH.sub.2 Pr 2-Me-3-Pyr -- 79-11 H CH.sub.2 H H
CH.sub.2 Pr 2-MeO-5-Pyr -- 79-12 H CH.sub.2 H H CH.sub.2 Pr
2-EtO-5-Pyr -- 79-13 H CH.sub.2 H H CH.sub.2 Pr 2-iPrO-5-Pyr --
79-14 H CH.sub.2 H H CH.sub.2 Pr 2-MeS-5-Pyr -- 79-15 H CH.sub.2 H
H CH.sub.2 Pr 2-EtS-5-Pyr -- 79-16 H CH.sub.2 H H CH.sub.2 Pr
2-Ph-5-Pyr -- 79-17 H CH.sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr --
[0343]
80TABLE 80 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
80-1 H CH.sub.2 H H CH.sub.2 Bu Ph 80-2 H CH.sub.2 H H CH.sub.2 Bu
4-Ph--Ph -- 80-3 H CH.sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph -- 80-4 H
CH.sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph -- 80-5 H CH.sub.2 H H
CH.sub.2 Bu 4-(Pyr-4)-Ph -- 80-6 H CH.sub.2 H H CH.sub.2 Bu 2-Pyr
-- 80-7 H CH.sub.2 H H CH.sub.2 Bu 3-Pyr -- 80-8 H CH.sub.2 H H
CH.sub.2 Bu 4-Pyr -- 80-9 H CH.sub.2 H H CH.sub.2 Bu 2-Me-5-Pyr --
80-10 H CH.sub.2 H H CH.sub.2 Bu 2-Me-3-Pyr -- 80-11 H CH.sub.2 H H
CH.sub.2 Bu 2-MeO-5-Pyr -- 80-12 H CH.sub.2 H H CH.sub.2 Bu
2-EtO-5-Pyr -- 80-13 H CH.sub.2 H H CH.sub.2 Bu 2-iPrO-5-Pyr --
80-14 H CH.sub.2 H H CH.sub.2 Bu 2-MeS-5-Pyr -- 80-15 H CH.sub.2 H
H CH.sub.2 Bu 2-EtS-5-Pyr -- 80-16 H CH.sub.2 H H CH.sub.2 Bu
2-Ph-5-Pyr -- 80-17 H CH.sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr --
[0344]
81TABLE 81 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
81-1 H CH.sub.2 H H CH.sub.2 Pen Ph -- 81-2 H CH.sub.2 H H CH.sub.2
Pen 4-Ph--Ph -- 81-3 H CH.sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph --
81-4 H CH.sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph -- 81-5 H CH.sub.2 H
H CH.sub.2 Pen 4-(Pyr-4)-Ph -- 81-6 H CH.sub.2 H H CH.sub.2 Pen
2-Pyr -- 81-7 H CH.sub.2 H H CH.sub.2 Pen 3-Pyr -- 81-8 H CH.sub.2
H H CH.sub.2 Pen 4-Pyr -- 81-9 H CH.sub.2 H H CH.sub.2 Pen
2-Me-5-Pyr -- 81-10 H CH.sub.2 H H CH.sub.2 Pen 2-Me-3-Pyr -- 81-11
H CH.sub.2 H H CH.sub.2 Pen 2-MeO-5-Pyr -- 81-12 H CH.sub.2 H H
CH.sub.2 Pen 2-EtO-5-Pyr -- 81-13 H CH.sub.2 H H CH.sub.2 Pen
2-iPrO-5-Pyr -- 81-14 H CH.sub.2 H H CH.sub.2 Pen 2-MeS-5-Pyr --
81-15 H CH.sub.2 H H CH.sub.2 Pen 2-EtS-5-Pyr -- 81-16 H CH.sub.2 H
H CH.sub.2 Pen 2-Ph-5-Pyr -- 81-17 H CH.sub.2 H H CH.sub.2 Pen
3-Ph-6-Pyr --
[0345]
82TABLE 82 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
82-1 H CH.sub.2 H H CH.sub.2 MeS Ph -- 82-2 H CH.sub.2 H H CH.sub.2
MeS 4-Ph--Ph -- 82-3 H CH.sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph --
82-4 H CH.sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph -- 82-5 H CH.sub.2 H
H CH.sub.2 MeS 4-(Pyr-4)-Ph -- 82-6 H CH.sub.2 H H CH.sub.2 MeS
2-Pyr -- 82-7 H CH.sub.2 H H CH.sub.2 MeS 3-Pyr -- 82-8 H CH.sub.2
H H CH.sub.2 MeS 4-Pyr -- 82-9 H CH.sub.2 H H CH.sub.2 MeS
2-Me-5-Pyr -- 82-10 H CH.sub.2 H H CH.sub.2 MeS 2-Me-3-Pyr -- 82-11
H CH.sub.2 H H CH.sub.2 MeS 2-MeO-5-Pyr -- 82-12 H CH.sub.2 H H
CH.sub.2 MeS 2-EtO-5-Pyr -- 82-13 H CH.sub.2 H H CH.sub.2 MeS
2-iPrO-5-Pyr -- 82-14 H CH.sub.2 H H CH.sub.2 MeS 2-MeS-5-Pyr --
82-15 H CH.sub.2 H H CH.sub.2 MeS 2-EtS-5-Pyr -- 82-16 H CH.sub.2 H
H CH.sub.2 MeS 2-Ph-5-Pyr -- 82-17 H CH.sub.2 H H CH.sub.2 MeS
3-Ph-6-Pyr --
[0346]
83TABLE 83 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
83-1 H CH.sub.2 H H CH.sub.2 PhO Ph -- 83-2 H CH.sub.2 H H CH.sub.2
PhO 4-Ph--Ph -- 83-3 H CH.sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph --
83-4 H CH.sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph -- 83-5 H CH.sub.2 H
H CH.sub.2 PhO 4-(Pyr-4)-Ph -- 83-6 H CH.sub.2 H H CH.sub.2 PhO
2-Pyr -- 83-7 H CH.sub.2 H H CH.sub.2 PhO 3-Pyr -- 83-8 H CH.sub.2
H H CH.sub.2 PhO 4-Pyr -- 83-9 H CH.sub.2 H H CH.sub.2 PhO
2-Me-5-Pyr -- 83-10 H CH.sub.2 H H CH.sub.2 PhO 2-Me-3-Pyr -- 83-11
H CH.sub.2 H H CH.sub.2 PhO 2-MeO-5-Pyr -- 83-12 H CH.sub.2 H H
CH.sub.2 PhO 2-EtO-5-Pyr -- 83-13 H CH.sub.2 H H CH.sub.2 PhO
2-iPrO-5-Pyr -- 83-14 H CH.sub.2 H H CH.sub.2 PhO 2-MeS-5-Pyr --
83-15 H CH.sub.2 H H CH.sub.2 PhO 2-EtS-5-Pyr -- 83-16 H CH.sub.2 H
H CH.sub.2 PhO 2-Ph-5-Pyr -- 83-17 H CH.sub.2 H H CH.sub.2 PhO
3-Ph-6-Pyr --
[0347]
84TABLE 84 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
84-1 H CH.sub.2 H H CH.sub.2 4-iPr- Ph -- PhO 84-2 H CH.sub.2 H H
CH.sub.2 4-iPr- 4-Ph-Ph -- PhO 84-3 H CH.sub.2 H H CH.sub.2 4-iPr-
4-(Pyr-2)-Ph -- PhO 84-4 H CH.sub.2 H H CH.sub.2 4-iPr-
4-(Pyr-3)-Ph -- PhO 84-5 H CH.sub.2 H H CH.sub.2 4-iPr-
4-(Pyr-4)-Ph -- PhO 84-6 H CH.sub.2 H H CH.sub.2 4-iPr- 2-Pyr --
PhO 84-7 H CH.sub.2 H H CH.sub.2 4-iPr- 3-Pyr -- PhO 84-8 H
CH.sub.2 H H CH.sub.2 4-iPr- 4-Pyr -- PhO 84-9 H CH.sub.2 H H
CH.sub.2 4-iPr- 2-Me-5-Pyr -- PhO 84-10 H CH.sub.2 H H CH.sub.2
4-iPr- 2-Me-3-Pyr -- PhO 84-11 H CH.sub.2 H H CH.sub.2 4-iPr-
2-MeO-5-Pyr -- PhO 84-12 H CH.sub.2 H H CH.sub.2 4-iPr- 2-EtO-5-Pyr
-- PhO 84-13 H CH.sub.2 H H CH.sub.2 4-iPr- 2-iPrO-5-Pyr -- PhO
84-14 H CH.sub.2 H H CH.sub.2 4-iPr- 2-MeS-5-Pyr -- PhO 84-15 H
CH.sub.2 H H CH.sub.2 4-iPr- 2-EtS-5-Pyr -- PhO 84-16 H CH.sub.2 H
H CH.sub.2 4-iPr- 2-Ph-5-Pyr -- PhO 84-17 H CH.sub.2 H H CH.sub.2
4-iPr- 3-Ph-6-Pyr -- PhO
[0348]
85TABLE 85 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
85-1 H CH.sub.2 H H CH.sub.2 4-MeO--PhO Ph -- 85-2 H CH.sub.2 H H
CH.sub.2 4-MeO--PhO 4-Ph--Ph -- 85-3 H CH.sub.2 H H CH.sub.2
4-MeO--PhO 4-(Pyr-2)-Ph -- 85-4 H CH.sub.2 H H CH.sub.2 4-MeO--PhO
4-(Pyr-3)-Ph -- 85-5 H CH.sub.2 H H CH.sub.2 4-MeO--PhO
4-(Pyr-4)-Ph -- 85-6 H CH.sub.2 H H CH.sub.2 4-MeO--PhO 2-Pyr --
85-7 H CH.sub.2 H H CH.sub.2 4-MeO--PhO 3-Pyr -- 85-8 H CH.sub.2 H
H CH.sub.2 4-MeO--PhO 4-Pyr -- 85-9 H CH.sub.2 H H CH.sub.2
4-MeO--PhO 2-Me-5-Pyr -- 85-10 H CH.sub.2 H H CH.sub.2 4-MeO--PhO
2-Me-3-Pyr -- 85-11 H CH.sub.2 H H CH.sub.2 4-MeO--PhO 2-MeO-5-Pyr
-- 85-12 H CH.sub.2 H H CH.sub.2 4-MeO--PhO 2-EtO-5-Pyr -- 85-13 H
CH.sub.2 H H CH.sub.2 4-MeO--PhO 2-iPrO-5-Pyr -- 85-14 H CH.sub.2 H
H CH.sub.2 4-MeO--PhO 2-MeS-5-Pyr -- 85-15 H CH.sub.2 H H CH.sub.2
4-MeO--PhO 2-EtS-5-Pyr -- 85-16 H CH.sub.2 H H CH.sub.2 4-MeO--PhO
2-Ph-5-Pyr -- 85-17 H CH.sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph-6-Pyr
--
[0349]
86TABLE 86 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
86-1 H CH.sub.2 H H CH.sub.2 PhS Ph -- 86-2 H CH.sub.2 H H CH.sub.2
PhS 4-Ph--Ph -- 86-3 H CH.sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph --
86-4 H CH.sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph -- 86-5 H CH.sub.2 H
H CH.sub.2 PhS 4-(Pyr-4)-Ph -- 86-6 H CH.sub.2 H H CH.sub.2 PhS
2-Pyr -- 86-7 H CH.sub.2 H H CH.sub.2 PhS 3-Pyr -- 86-8 H CH.sub.2
H H CH.sub.2 PhS 4-Pyr -- 86-9 H CH.sub.2 H H CH.sub.2 PhS
2-Me-5-Pyr -- 86-10 H CH.sub.2 H H CH.sub.2 PhS 2-Me-3-Pyr -- 86-11
H CH.sub.2 H H CH.sub.2 PhS 2-MeO-5-Pyr -- 86-12 H CH.sub.2 H H
CH.sub.2 PhS 2-EtO-5-Pyr -- 86-13 H CH.sub.2 H H CH.sub.2 PhS
2-iPrO-5-Pyr -- 86-14 H CH.sub.2 H H CH.sub.2 PhS 2-MeS-5-Pyr --
86-15 H CH.sub.2 H H CH.sub.2 PhS 2-EtS-5-Pyr -- 86-16 H CH.sub.2 H
H CH.sub.2 PhS 2-Ph-5-Pyr -- 86-17 H CH.sub.2 H H CH.sub.2 PhS
3-Ph-6-Pyr --
[0350]
87TABLE 87 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
87-1 H CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 Ph -- 87-2 H
CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph -- 87-3 H
CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph -- 87-4 H
CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph -- 87-5 H
CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph -- 87-6 H
CH.sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Pyr -- 87-7 H CH.sub.2 H
H CH.sub.2 Ph(CH.sub.2).sub.3 3-Pyr -- 87-8 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-Pyr -- 87-9 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-Me-5-Pyr -- 87-10 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-Me-3-Pyr -- 87-11 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-MeO-5-Pyr -- 87-12 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-EtO-5-Pyr -- 87-13 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-iPrO-5-Pyr -- 87-14 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-MeS-5-Pyr -- 87-15 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-EtS-5-Pyr -- 87-16 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 2-Ph-5-Pyr -- 87-17 H CH.sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 3-Ph-6-Pyr --
[0351]
88TABLE 88 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
88-1 H CH.sub.2 H Me CH.sub.2 EtO 4-Ph--Ph -- 88-2 H CH.sub.2 H Me
CH.sub.2 EtO 4-(Pyr-2)-Ph -- 88-3 H CH.sub.2 H Me CH.sub.2 EtO
4-(Pyr-3)-Ph -- 88-4 H CH.sub.2 H Me CH.sub.2 EtO 4-(Pyr-4)-Ph --
88-5 H CH.sub.2 H Me CH.sub.2 EtO 2-Ph-5-Pyr -- 88-6 H CH.sub.2 H
Me CH.sub.2 EtO 3-Ph-6-Pyr --
[0352]
89TABLE 89 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
89-1 H CH.sub.2 H Me CH.sub.2 Pr 4-Ph--Ph -- 89-2 H CH.sub.2 H Me
CH.sub.2 Pr 4-(Pyr-2)-Ph -- 89-3 H CH.sub.2 H Me CH.sub.2 Pr
4-(Pyr-3)-Ph -- 89-4 H CH.sub.2 H Me CH.sub.2 Pr 4-(Pyr-4)-Ph --
89-5 H CH.sub.2 H Me CH.sub.2 Pr 2-Ph-5-Pyr -- 89-6 H CH.sub.2 H Me
CH.sub.2 Pr 3-Ph-6-Pyr --
[0353]
90TABLE 90 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
90-1 H CH.sub.2 H Me CH.sub.2 Bu 4-Ph--Ph -- 90-2 H CH.sub.2 H Me
CH.sub.2 Bu 4-(Pyr-2)-Ph -- 90-3 H CH.sub.2 H Me CH.sub.2 Bu
4-(Pyr-3)-Ph -- 90-4 H CH.sub.2 H Me CH.sub.2 Bu 4-(Pyr-4)-Ph --
90-5 H CH.sub.2 H Me CH.sub.2 Bu 2-Ph-5-Pyr -- 90-6 H CH.sub.2 H Me
CH.sub.2 Bu 3-Ph-6-Pyr --
[0354]
91TABLE 91 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
91-1 H CH.sub.2 H Me CH.sub.2 Pen 4-Ph--Ph -- 91-2 H CH.sub.2 H Me
CH.sub.2 Pen 4-(Pyr-2)-Ph -- 91-3 H CH.sub.2 H Me CH.sub.2 Pen
4-(Pyr-3)-Ph -- 91-4 H CH.sub.2 H Me CH.sub.2 Pen 4-(Pyr-4)-Ph --
91-5 H CH.sub.2 H Me CH.sub.2 Pen 2-Ph-5-Pyr -- 91-6 H CH.sub.2 H
Me CH.sub.2 Pen 3-Ph-6-Pyr --
[0355]
92TABLE 92 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
92-1 H CH.sub.2 H Me CH.sub.2 MeS 4-Ph-Ph -- 92-2 H CH.sub.2 H Me
CH.sub.2 MeS 4-(Pyr-2)-Ph -- 92-3 H CH.sub.2 H Me CH.sub.2 MeS
4-(Pyr-3)-Ph -- 92-4 H CH.sub.2 H Me CH.sub.2 MeS 4-(Pyr-4)-Ph --
92-5 H CH.sub.2 H Me CH.sub.2 MeS 2-Ph-5-Pyr -- 92-6 H CH.sub.2 H
Me CH.sub.2 MeS 3-Ph-6-Pyr --
[0356]
93TABLE 93 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
93-1 H CH.sub.2 H Me CH.sub.2 PhO 4-Ph--Ph -- 93-2 H CH.sub.2 H Me
CH.sub.2 PhO 4-(Pyr-2)-Ph -- 93-3 H CH.sub.2 H Me CH.sub.2 PhO
4-(Pyr-3)-Ph -- 93-4 H CH.sub.2 H Me CH.sub.2 PhO 4-(Pyr-4)-Ph --
93-5 H CH.sub.2 H Me CH.sub.2 PhO 2-Ph-5-Pyr -- 93-6 H CH.sub.2 H
Me CH.sub.2 PhO 3-Ph-6-Pyr --
[0357]
94TABLE 94 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
94-1 H CH.sub.2 H Me CH.sub.2 4-iPr--PhO 4-Ph--Ph -- 94-2 H
CH.sub.2 H Me CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph -- 94-3 H CH.sub.2 H
Me CH.sub.2 4-iPr--PhO 4-(Pyr-3)-Ph -- 94-4 H CH.sub.2 H Me
CH.sub.2 4-iPr--PhO 4-(Pyr-4)-Ph -- 94-5 H CH.sub.2 H Me CH.sub.2
4-iPr--PhO 2-Ph-5-Pyr -- 94-6 H CH.sub.2 H Me CH.sub.2 4-iPr--PhO
3-Ph-6-Pyr --
[0358]
95TABLE 95 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
95-1 H CH.sub.2 H Me CH.sub.2 4-MeO--PhO 4-Ph--Ph -- 95-2 H
CH.sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph -- 95-3 H CH.sub.2 H
Me CH.sub.2 4-MeO--PhO 4-(Pyr-3)-Ph -- 95-4 H CH.sub.2 H Me
CH.sub.2 4-MeO--PhO 4-(Pyr-4)-Ph -- 95-5 H CH.sub.2 H Me CH.sub.2
4-MeO--PhO 2-Ph-5-Pyr -- 95-6 H CH.sub.2 H Me CH.sub.2 4-MeO--PhO
3-Ph-6-Pyr --
[0359]
96TABLE 96 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
96-1 H CH.sub.2 H Me CH.sub.2 PhS 4-Ph--Ph -- 96-2 H CH.sub.2 H Me
CH.sub.2 PhS 4-(Pyr-2)-Ph -- 96-3 H CH.sub.2 H Me CH.sub.2 PhS
4-(Pyr-3)-Ph -- 96-4 H CH.sub.2 H Me CH.sub.2 PhS 4-(Pyr-4)-Ph --
96-5 H CH.sub.2 H Me CH.sub.2 PhS 2-Ph-5-Pyr -- 96-6 H CH.sub.2 H
Me CH.sub.2 PhS 3-Ph-6-Pyr --
[0360]
97TABLE 97 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
97-1 H CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph -- 97-2 H
CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-2)-Ph -- 97-3 H
CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph -- 97-4 H
CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph -- 97-5 H
CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr -- 97-6 H
CH.sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr --
[0361]
98TABLE 98 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
98-1 H (CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-Ph--Ph -- 98-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-2)-Ph -- 98-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-3)-Ph -- 98-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 4-(Pyr-4)-Ph -- 98-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 2-Ph-5-Pyr -- 98-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 EtO 3-Ph-6-Pyr --
[0362]
99TABLE 99 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
99-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-Ph--Ph -- 99-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-2)-Ph -- 99-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-3)-Ph -- 99-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 4-(Pyr-4)-Ph -- 99-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 2-Ph-5-Pyr -- 99-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pr 3-Ph-6-Pyr --
[0363]
100TABLE 100 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
100-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-Ph--Ph -- 100-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-2)-Ph -- 100-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-3)-Ph -- 100-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 4-(Pyr-4)-Ph -- 100-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 2-Ph-5-Pyr -- 100-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Bu 3-Ph-6-Pyr --
[0364]
101TABLE 101 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
101-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-Ph--Ph -- 101-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-2)-Ph -- 101-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-3)-Ph -- 101-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 4-(Pyr-4)-Ph -- 101-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 2-Ph-5-Pyr -- 101-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 Pen 3-Ph-6-Pyr --
[0365]
102TABLE 102 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
102-1 H (CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-Ph--Ph -- 102-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-2)-Ph -- 102-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-3)-Ph -- 102-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 4-(Pyr-4)-Ph -- 102-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 2-Ph-5-Pyr -- 102-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 MeS 3-Ph-6-Pyr --
[0366]
103TABLE 103 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
103-1 H (CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-Ph--Ph -- 103-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-2)-Ph -- 103-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-3)-Ph -- 103-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 4-(Pyr-4)-Ph -- 103-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 2-Ph-5-Pyr -- 103-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhO 3-Ph-6-Pyr --
[0367]
104TABLE 104 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
104-1 H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 4-Ph--Ph -- 104-2
H (CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 4-(Pyr-2)-Ph -- 104-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 4-(Pyr-3)-Ph -- 104-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 4-(Pyr-4)-Ph -- 104-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 2-Ph-5-Pyr -- 104-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-iPr-PhO 3-Ph-6-Pyr --
[0368]
105TABLE 105 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
105-1 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-Ph--Ph -- 105-2
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-2)- -- Ph 105-3
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-3)- -- Ph 105-4
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 4-(Pyr-4)- -- Ph 105-5
H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 2-Ph-5- -- Pyr 105-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeO--PhO 3-Ph-6- -- Pyr
[0369]
106TABLE 106 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
106-1 H (CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-Ph--Ph -- 106-2 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-2)-Ph -- 106-3 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-3)-Ph -- 106-4 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 4-(Pyr-4)-Ph -- 106-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 2-Ph-5-Pyr -- 106-6 H
(CH.sub.2).sub.2 H Me CH.sub.2 PhS 3-Ph-6-Pyr --
[0370]
107TABLE 107 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
107-1 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph
-- 107-2 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-2)-Ph -- 107-3 H (CH.sub.2).sub.2 H Me CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph -- 107-4 H (CH.sub.2).sub.2 H Me
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph -- 107-5 H
(CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr --
107-6 H (CH.sub.2).sub.2 H Me CH.sub.2 Ph(CH.sub.2).sub.3
3-Ph-6-Pyr --
[0371]
108TABLE 108 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
108-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph S 108-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph S 108-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph S 108-4 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph S 108-5 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr S 108-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr S
[0372]
109TABLE 109 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
109-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph-Ph S 109-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph S 109-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph S 109-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph S 109-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr S 109-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr S
[0373]
110TABLE 110 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
110-1 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph S 110-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph S 110-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph S 110-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph S 110-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr S 110-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr S
[0374]
111TABLE 111 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
111-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph S 111-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph S 111-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph S 111-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph S 111-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr S 111-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr S
[0375]
112TABLE 112 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
112-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph--Ph S 112-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph S 112-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph S 112-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph S 112-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr S 112-6 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr S
[0376]
113TABLE 113 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
113-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph--Ph S 113-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph S 113-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph S 113-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph S 113-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr S 113-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr S
[0377]
114TABLE 114 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
114-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-Ph--Ph S 114-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-2)-Ph S 114-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-3)-Ph S 114-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-4)-Ph S 114-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 2-Ph-5-Pyr S 114-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 3-Ph-6-Pyr S
[0378]
115TABLE 115 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
115-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-Ph--Ph S 115-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-2)- S Ph 115-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-3)- S Ph 115-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 4-(Pyr-4)- S Ph 115-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 2-Ph-5- S Pyr 115-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO--PhO 3-Ph-6- S Pyr
[0379]
116TABLE 116 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
116-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph--Ph S 116-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph S 116-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph S 116-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph S 116-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr S 116-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr S
[0380]
117TABLE 117 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
117-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph S
117-2 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-2)-Ph S 117-3 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph S 117-4 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph S 117-5 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr S 117-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr S
[0381]
118TABLE 118 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
118-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph NMe 118-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph NMe 118-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph NMe 118-4 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph NMe 118-5 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr NMe 118-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr NMe
[0382]
119TABLE 119 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
119-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph--Ph NMe 119-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph NMe 119-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph NMe 119-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph NMe 119-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr NMe 119-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr NMe
[0383]
120TABLE 120 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
120-1 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph NMe 120-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph NMe 120-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph NMe 120-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph NMe 120-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr NMe 120-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr NMe
[0384]
121TABLE 121 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
121-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph NMe 121-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph NMe 121-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph NMe 121-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph NMe 121-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr NMe 121-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr NMe
[0385]
122TABLE 122 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
122-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph--Ph NMe 122-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph NMe 122-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph NMe 122-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph NMe 122-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr NMe 122-6 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr NMe
[0386]
123TABLE 123 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
123-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph--Ph NMe 123-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph NMe 123-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph NMe 123-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph NMe 123-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr NMe 123-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr NMe
[0387]
124TABLE 124 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
124-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-Ph-Ph NMe 124-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-2)-Ph NMe 124-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-3)-Ph NMe 124-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-4)-Ph NMe 124-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 2-Ph-5-Pyr NMe 124-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 3-Ph-6-Pyr NMe
[0388]
125TABLE 125 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
125-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 4-Ph--Ph NMe PhO
125-2 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 4-(Pyr-2)- NMe PhO Ph
125-3 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 4-(Pyr-3)- NMe PhO Ph
125-4 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 4-(Pyr-4)- NMe PhO Ph
125-5 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 2-Ph-5- NMe PhO Pyr
125-6 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-- 3-Ph-6- NMe PhO
Pyr
[0389]
126TABLE 126 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
126-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph--Ph NMe 126-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph NMe 126-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph NMe 126-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph NMe 126-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr NMe 126-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr NMe
[0390]
127TABLE 127 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
127-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph-Ph
NMe 127-2 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-2)-Ph NMe 127-3 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph NMe 127-4 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph NMe 127-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr NMe
127-6 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr
NMe
[0391]
128TABLE 128 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
128-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph--Ph NAc 128-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph NAc 128-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph NAc 128-4 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph NAc 128-5 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr NAc 128-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr NAc
[0392]
129TABLE 129 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
129-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph--Ph NAc 129-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph NAc 129-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph NAc 129-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph NAc 129-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr NAc 129-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr NAc
[0393]
130TABLE 130 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
130-1 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph--Ph NAc 130-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph NAc 130-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph NAc 130-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph NAc 130-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr NAc 130-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr NAc
[0394]
131TABLE 131 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
131-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph--Ph NAc 131-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph NAc 131-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph NAc 131-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph NAc 131-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr NAc 131-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr NAc
[0395]
132TABLE 132 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
132-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph--Ph NAc 132-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph NAc 132-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph NAc 132-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph NAc 132-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr NAc 132-6 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr NAc
[0396]
133TABLE 133 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
133-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph-Ph NAc 133-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph NAc 133-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph NAc 133-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph NAc 133-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr NAc 133-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr NAc
[0397]
134TABLE 136 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
136-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph--Ph NAc 136-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph NAc 136-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph NAc 136-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph NAc 136-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr NAc 136-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr NAc
[0398]
135TABLE 137 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
137-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph--Ph
NAc 137-2 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-2)-Ph NAc 137-3 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph NAc 137-4 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph NAc 137-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr NAc
137-6 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr
NAc
[0399]
136TABLE 138 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
138-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhOCH.sub.2 4-(Pyr-2)-Ph O
138-2 H (CH.sub.2).sub.2 H H CH.sub.2 PhO(CH.sub.2).sub.2
4-(Pyr-2)-Ph O 138-3 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
4-Ph--Ph O 138-4 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
4-(4-HO--Ph)--Ph O 138-5 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
4-(4-MeO--Ph)--Ph O 138-6 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(4-F--Ph)--Ph O 138-7 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(4-Cl--Ph)--Ph O 138-8 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(Pyr-2)-Ph O 138-9 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(Pyr-3)-Ph O 138-10 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(Pyr-4)-Ph O 138-11 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(3-MeO-Pyr-6)-Ph O 138-12 H (CH.sub.2).sub.2 H H
CH.sub.2 4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 138-13 H (CH.sub.2).sub.2
H H CH.sub.2 4-tBu--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-14 H
(CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
138-15 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO 2-Ph-5-Pyr O
138-16 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr
O 138-17 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
2-(4-MeO--Ph)-5-Pyr O 138-18 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 2-TfpO-5-Pyr O 138-19 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 4-Ph--Ph O 138-20 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 4-(4-HO--Ph)--Ph O 138-21 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3--PhO 4-(4-MeO--Ph)--Ph O 138-22 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 4-(4-F--Ph)--Ph O
138-23 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO
4-(4-Cl--Ph)--Ph O 138-24 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 4-(Pyr-2)-Ph O 138-25 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-3)-Ph O 138-26 H (CH.sub.2).sub.2 H
H CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-4)-Ph O 138-27 H (CH.sub.2).sub.2
H H CH.sub.2 4-CF.sub.3--PhO 4-(3-MeO-Pyr-6)-Ph O 138-28 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O
138-29 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 138-30 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-31 H (CH.sub.2).sub.2
H H CH.sub.2 4-CF.sub.3--PhO 2-Ph-5-Pyr O 138-32 H (CH.sub.2).sub.2
H H CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 138-33 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 2-(4-MeO--Ph)-5-Pyr O
138-34 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 2-TfpO-5-Pyr
O 138-35 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 4-Ph--Ph
O 138-36 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
4-(4-HO--Ph)--Ph O 138-37 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 4-(4-MeO--Ph)--Ph O 138-38 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3O--PhO 4-(4-F--Ph)--Ph O 138-39 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 4-(4-Cl--Ph)--Ph O
138-40 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
4-(Pyr-2)-Ph O 138-41 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 4-(Pyr-3)-Ph O 138-42 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3O--PhO 4-(Pyr-4)-Ph O 138-43 H (CH.sub.2).sub.2
H H CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph O 138-44 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 4-(3-Dma-Pyr-6)-Ph O
138-45 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 138-46 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-47 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 2-Ph-5-Pyr O 138-48
H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 2-(4-F--Ph)-5-Pyr
O 138-49 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
2-(4-MeO--Ph)-5-Pyr O 138-50 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 2-TfpO-5-Pyr O 138-51 H (CH.sub.2).sub.2 H H
CH.sub.2 4-F--PhO 4-Ph--Ph O 138-52 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-HO--Ph)--Ph O 138-53 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-MeO--Ph)--Ph O 138-54 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-F--Ph)--Ph O 138-55 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-Cl--Ph)--Ph O 138-56 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(Pyr-2)-Ph O 138-57 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(Pyr-3)-Ph O 138-58 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(Pyr-4)-Ph O 138-59 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 138-60 H (CH.sub.2).sub.2 H H
CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O 138-61 H (CH.sub.2).sub.2 H
H CH.sub.2 4-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-62 H
(CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
138-63 H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-Ph-5-Pyr O 138-64
H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr O 138-65
H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-(4-MeO--Ph)-5-Pyr O
138-66 H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-TfpO-5-Pyr O
138-67 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-Ph--Ph O 138-68
H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(4-HO--Ph)--Ph O 138-69
H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(4-MeO--Ph)--Ph O
138-70 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(4-F--Ph)--Ph O
138-71 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(4-Cl--Ph)--Ph O
138-72 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(Pyr-2)-Ph O
138-73 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(Pyr-3)-Ph O
138-74 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(Pyr-4)-Ph O
138-75 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph
O 138-76 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO
4-(3-Dma-Pyr-6)-Ph O 138-77 H (CH.sub.2).sub.2 H H CH.sub.2
4-Cl--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-78 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Cl--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-79 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 2-Ph-5-Pyr O 138-80 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 2-(4-F--Ph)-5-Pyr O 138-81
H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O
138-82 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O
138-83 H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-Ph--Ph O 138-84 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(4-HO--Ph)--Ph O 138-85 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(4-MeO--Ph)--Ph O 138-86 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(4-F--Ph)--Ph O 138-87 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(4-Cl--Ph)--Ph O 138-88 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 138-89 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(Pyr-3)-Ph O 138-90 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(Pyr-4)-Ph O 138-91 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 138-92
H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O
138-93 H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 138-94 H (CH.sub.2).sub.2 H H CH.sub.2
3-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-95 H (CH.sub.2).sub.2 H H
CH.sub.2 3-F--PhO 2-Ph-5-Pyr O 138-96 H (CH.sub.2).sub.2 H H
CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr O 138-97 H (CH.sub.2).sub.2 H H
CH.sub.2 3-F--PhO 2-(4-MeO--Ph)-5-Pyr O 138-98 H (CH.sub.2).sub.2 H
H CH.sub.2 3-F--PhO 2-TfpO-5-Pyr O 138-99 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CN--PhO 4-Ph--Ph O 138-100 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CN--PhO 4-(4-HO--Ph)--Ph O 138-101 H (CH.sub.2).sub.2 H
H CH.sub.2 4-CN--PhO 4-(4-MeO--Ph)--Ph O 138-102 H (CH.sub.2).sub.2
H H CH.sub.2 4-CN--PhO 4-(4-F--Ph)--Ph O 138-103 H (CH.sub.2).sub.2
H H CH.sub.2 4-CN--PhO 4-(4-Cl--Ph)--Ph O 138-104 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 4-(Pyr-2)-Ph O 138-105 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 4-(Pyr-3)-Ph O 138-106 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 4-(Pyr-4)-Ph O 138-107 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 4-(3-MeO-Pyr-6)-Ph O
138-108 H (CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO
4-(3-Dma-Pyr-6)-Ph O 138-109 H (CH.sub.2).sub.2 H H CH.sub.2
4-CN--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-110 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CN--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-111 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 2-Ph-5-Pyr O 138-112 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 2-(4-F--Ph)-5-Pyr O 138-113
H (CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 2-(4-MeO--Ph)-5-Pyr O
138-114 H (CH.sub.2).sub.2 H H CH.sub.2 4-CN--PhO 2-TfpO-5-Pyr O
138-115 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO 4-Ph--Ph O
138-116 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO 4-(4-HO--Ph)--Ph
O 138-117 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO
4-(4-MeO--Ph)--Ph O 138-118 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeS--PhO 4-(4-F--Ph)--Ph O 138-119 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeS--PhO 4-(4-Cl--Ph)--Ph O 138-120 H (CH.sub.2).sub.2 H
H CH.sub.2 4-MeS--PhO 4-(Pyr-2)-Ph O 138-121 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeS--PhO 4-(Pyr-3)-Ph O 138-122 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeS--PhO 4-(Pyr-4)-Ph O 138-123 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeS--PhO 4-(3-MeO-Pyr-6)-Ph O 138-124 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeS--PhO 4-(3-Dma-Pyr-6)-Ph O 138-125 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O
138-126 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 138-127 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeS--PhO 2-Ph-5-Pyr O 138-128 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeS--PhO 2-(4-F--Ph)-5-Pyr O 138-129 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeS--PhO 2-(4-MeO--Ph)-5-Pyr O 138-130 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeS--PhO 2-TfpO-5-Pyr O 138-131 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO 4-Ph--Ph O 138-132
H (CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO 4-(4-HO--Ph)--Ph
O 138-133 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO
4-(4-MeO--Ph)--Ph O 138-134 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeSO.sub.2--PhO 4-(4-F--Ph)--Ph O 138-135 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeSO.sub.2--PhO 4-(4-Cl--Ph)--Ph O 138-136 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO 4-(Pyr-2)-Ph O
138-137 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO
4-(Pyr-3)-Ph O 138-138 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeSO.sub.2--PhO 4-(Pyr-4)-Ph O 138-139 H (CH.sub.2).sub.2 H H
CH.sub.2 4-MeSO.sub.2--PhO 4-(3-MeO-Pyr-6)-Ph O 138-140 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO 4-(3-Dma-Pyr-6)-Ph
O 138-141 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 138-142 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeSO.sub.2--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-143 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO 2-Ph-5-Pyr O
138-144 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeSO.sub.2--PhO
2-(4-F--Ph)-5-Pyr O 138-145 H (CH.sub.2).sub.2 H H CH.sub.2
4-MeSO.sub.2--PhO 2-(4-MeO--Ph)-5-Pyr O 138-146 H (CH.sub.2).sub.2
H H CH.sub.2 4-MeSO.sub.2--PhO 2-TfpO-5-Pyr O 138-147 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-Ph--Ph O 138-148 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-(4-HO--Ph)--Ph O
138-149 H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO
4-(4-MeO--Ph)--Ph O 138-150 H (CH.sub.2).sub.2 H H CH.sub.2
3,4-di-F--PhO 4-(4-F--Ph)--Ph O 138-151 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4-di-F--PhO 4-(4-Cl--Ph)--Ph O 138-152 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-(Pyr-2)-Ph O 138-153
H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-(Pyr-3)-Ph O
138-154 H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-(Pyr-4)-Ph
O 138-155 H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO
4-(3-MeO-Pyr-6)-Ph O 138-156 H (CH.sub.2).sub.2 H H CH.sub.2
3,4-di-F--PhO 4-(3-Dma-Pyr-6)-Ph O 138-157 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4-di-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-158 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph
O 138-159 H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO 2-Ph-5-Pyr
O 138-160 H (CH.sub.2).sub.2 H H CH.sub.2 3,4-di-F--PhO
2-(4-F--Ph)-5-Pyr O 138-161 H (CH.sub.2).sub.2 H H CH.sub.2
3,4-di-F--PhO 2-(4-MeO--Ph)-5-Pyr O 138-162 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4-di-F--PhO 2-TfpO-5-Pyr O 138-163 H (CH.sub.2).sub.2 H
H CH.sub.2 3,5-di-F--PhO 4-Ph--Ph O 138-164 H (CH.sub.2).sub.2 H H
CH.sub.2 3,5-di-F--PhO 4-(4-HO--Ph)--Ph O 138-165 H
(CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO 4-(4-MeO--Ph)--Ph O
138-166 H (CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO
4-(4-F--Ph)--Ph O 138-167 H (CH.sub.2).sub.2 H H CH.sub.2
3,5-di-F--PhO 4-(4-Cl--Ph)--Ph O 138-168 H (CH.sub.2).sub.2 H H
CH.sub.2 3,5-di-F--PhO 4-(Pyr-2)-Ph O 138-169 H (CH.sub.2).sub.2 H
H CH.sub.2 3,5-di-F--PhO 4-(Pyr-3)-Ph O 138-170 H (CH.sub.2).sub.2
H H CH.sub.2 3,5-di-F--PhO 4-(Pyr-4)-Ph O 138-171 H
(CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO 4-(3-MeO-Pyr-6)-Ph O
138-172 H (CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO
4-(3-Dma-Pyr-6)-Ph O 138-173 H (CH.sub.2).sub.2 H H CH.sub.2
3,5-di-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-174 H (CH.sub.2).sub.2
H H CH.sub.2 3,5-di-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-175 H
(CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO 2-Ph-5-Pyr O 138-176 H
(CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO 2-(4-F--Ph)-5-Pyr O
138-177 H (CH.sub.2).sub.2 H H CH.sub.2 3,5-di-F--PhO
2-(4-MeO--Ph)-5-Pyr O 138-178 H (CH.sub.2).sub.2 H H CH.sub.2
3,5-di-F--PhO 2-TfpO-5-Pyr O 138-179 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4,5-tri-F--PhO 4-Ph--Ph O 138-180 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4,5-tri-F--PhO 4-(4-HO--Ph)--Ph O 138-181 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO 4-(4-MeO--Ph)--Ph O
138-182 H (CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO
4-(4-F--Ph)--Ph O 138-183 H (CH.sub.2).sub.2 H H CH.sub.2
3,4,5-tri-F--PhO 4-(4-Cl--Ph)--Ph O 138-184 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4,5-tri-F--PhO 4-(Pyr-2)-Ph O 138-185 H (CH.sub.2).sub.2
H H CH.sub.2 3,4,5-tri-F--PhO 4-(Pyr-3)-Ph O 138-186 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO 4-(Pyr-4)-Ph O
138-187 H (CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO
4-(3-MeO-Pyr-6)-Ph O 138-188 H (CH.sub.2).sub.2 H H CH.sub.2
3,4,5-tri-F--PhO 4-(3-Dma-Pyr-6)-Ph O 138-189 H (CH.sub.2).sub.2 H
H CH.sub.2 3,4,5-tri-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-190 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 138-191 H (CH.sub.2).sub.2 H H CH.sub.2
3,4,5-tri-F--PhO 2-Ph-5-Pyr O 138-192 H (CH.sub.2).sub.2 H H
CH.sub.2 3,4,5-tri-F--PhO 2-(4-F--Ph)-5-Pyr O 138-193 H
(CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO 2-(4-MeO--Ph)-5-Pyr
O 138-194 H (CH.sub.2).sub.2 H H CH.sub.2 3,4,5-tri-F--PhO
2-TfpO-5-Pyr O 138-195 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 4-Ph--Ph O 138-196 H (CH.sub.2).sub.2 H H
CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(4-HO--Ph)--Ph O 138-197 H
(CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(4-MeO--Ph)--Ph O 138-198 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(4-F--Ph)--Ph O 138-199 H (CH.sub.2).sub.2
H H CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(4-Cl--Ph)--Ph O 138-200 H
(CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(Pyr-2)-Ph O
138-201 H (CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(Pyr-3)-Ph O 138-202 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(Pyr-4)-Ph O 138-203 H (CH.sub.2).sub.2 H
H CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(3-MeO-Pyr-6)-Ph O 138-204 H
(CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(3-Dma-Pyr-6)-Ph O 138-205 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-206 H
(CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 138-207 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 2-Ph-5-Pyr O 138-208 H (CH.sub.2).sub.2 H H
CH.sub.2 2,3,4,5,6-penta-F--PhO 2-(4-F--Ph)-5-Pyr O 138-209 H
(CH.sub.2).sub.2 H H CH.sub.2 2,3,4,5,6-penta-F--PhO
2-(4-MeO--Ph)-5-Pyr O 138-210 H (CH.sub.2).sub.2 H H CH.sub.2
2,3,4,5,6-penta-F--PhO 2-TfpO-5-Pyr O 138-211 H (CH.sub.2).sub.2 H
H CH.sub.2 3-PyrO 4-Ph--Ph O 138-212 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(4-HO--Ph)--Ph O 138-213 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(4-MeO--Ph)--Ph O 138-214 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(4-F--Ph)--Ph O 138-215 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(4-Cl--Ph)--Ph O 138-216 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(Pyr-2)-Ph O 138-217 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(Pyr-3)-Ph O 138-218 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(Pyr-4)-Ph O 138-219 H (CH.sub.2).sub.2 H H
CH.sub.2 3-PyrO 4-(3-MeO-Pyr-6)-Ph O 138-220
H (CH.sub.2).sub.2 H H CH.sub.2 3-PyrO 4-(3-Dma-Pyr-6)-Ph O 138-221
H (CH.sub.2).sub.2 H H CH.sub.2 3-PyrO 4-(3-CF.sub.3-Pyr-6)-Ph O
138-222 H (CH.sub.2).sub.2 H H CH.sub.2 3-PyrO
4-(3-O.sub.2N-Pyr-6)-Ph O 138-223 H (CH.sub.2).sub.2 H H CH.sub.2
3-PyrO 2-Ph-5-Pyr O 138-224 H (CH.sub.2).sub.2 H H CH.sub.2 3-PyrO
2-(4-F--Ph)-5-Pyr O 138-225 H (CH.sub.2).sub.2 H H CH.sub.2 3-PyrO
2-(4-MeO--Ph)-5-Pyr O 138-226 H (CH.sub.2).sub.2 H H CH.sub.2
3-PyrO 2-TfpO-5-Pyr O 138-227 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-Ph--Ph O 138-228 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(4-HO--Ph)--Ph O 138-229 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(4-MeO--Ph)--Ph O 138-230 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(4-F--Ph)--Ph O 138-231 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(4-Cl--Ph)--Ph O 138-232 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(Pyr-2)-Ph O 138-233 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(Pyr-3)-Ph O 138-234 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(Pyr-4)-Ph O 138-235 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(3-MeO-Pyr-6)-Ph O 138-236 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(3-Dma-Pyr-6)-Ph O 138-237 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
4-(3-CF.sub.3-Pyr-6)-Ph O 138-238 H (CH.sub.2).sub.2 H H CH.sub.2
BzO 4-(3-O.sub.2N-Pyr-6)-Ph O 138-239 H (CH.sub.2).sub.2 H H
CH.sub.2 BzO 2-Ph-5-Pyr O 138-240 H (CH.sub.2).sub.2 H H CH.sub.2
BzO 2-(4-F--Ph)-5-Pyr O 138-241 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
2-(4-MeO--Ph)-5-Pyr O 138-242 H (CH.sub.2).sub.2 H H CH.sub.2 BzO
2-TfpO-5-Pyr O 138-243 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-Ph--Ph O 138-244 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(4-HO--Ph)--Ph O 138-245 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(4-MeO--Ph)--Ph O 138-246 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(4-F--Ph)--Ph O 138-247 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(4-Cl--Ph)--Ph O 138-248 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(Pyr-2)-Ph O 138-249 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(Pyr-3)-Ph O 138-250 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(Pyr-4)-Ph O 138-251 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS
4-(3-MeO-Pyr-6)-Ph O 138-252 H (CH.sub.2).sub.2 H H CH.sub.2
2-BoxaS 4-(3-Dma-Pyr-6)-Ph O 138-253 H (CH.sub.2).sub.2 H H
CH.sub.2 2-BoxaS 4-(3-CF.sub.3-Pyr-6)-Ph O 138-254 H
(CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS 4-(3-O.sub.2N-Pyr-6)-Ph O
138-255 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS 2-Ph-5-Pyr O
138-256 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS 2-(4-F--Ph)-5-Pyr O
138-257 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS 2-(4-MeO--Ph)-5-Pyr
O 138-258 H (CH.sub.2).sub.2 H H CH.sub.2 2-BoxaS 2-TfpO-5-Pyr O
138-259 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 4-Ph--Ph O
138-260 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO
4-(4-HO--Ph)--Ph O 138-261 H (CH.sub.2).sub.2 H H CH.sub.2
4-(Pyr-2)-PhO 4-(4-MeO--Ph)--Ph O 138-262 H (CH.sub.2).sub.2 H H
CH.sub.2 4-(Pyr-2)-PhO 4-(4-F--Ph)--Ph O 138-263 H (CH.sub.2).sub.2
H H CH.sub.2 4-(Pyr-2)-PhO 4-(4-Cl--Ph)--Ph O 138-264 H
(CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 4-(Pyr-2)-Ph O 138-265
H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 4-(Pyr-3)-Ph O
138-266 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 4-(Pyr-4)-Ph
O 138-267 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO
4-(3-MeO-Pyr-6)-Ph O 138-268 H (CH.sub.2).sub.2 H H CH.sub.2
4-(Pyr-2)-PhO 4-(3-Dma-Pyr-6)-Ph O 138-269 H (CH.sub.2).sub.2 H H
CH.sub.2 4-(Pyr-2)-PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 138-270 H
(CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 4-(3-O.sub.2N-Pyr-6)-Ph
O 138-271 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO 2-Ph-5-Pyr
O 138-272 H (CH.sub.2).sub.2 H H CH.sub.2 4-(Pyr-2)-PhO
2-(4-F--Ph)-5-Pyr O 138-273 H (CH.sub.2).sub.2 H H CH.sub.2
4-(Pyr-2)-PhO 2-(4-MeO--Ph)-5-Pyr O 138-274 H (CH.sub.2).sub.2 H H
CH.sub.2 4-(Pyr-2)-PhO 2-TfpO-5-Pyr O 138-275 H (CH.sub.2).sub.2 H
H CH.sub.2 4-tBu--PhO 4-(4-Me--Ph)--Ph O 138-276 H (CH.sub.2).sub.2
H H CH.sub.2 4-tBu--PhO 4-(4-Dma-Ph)--Ph O 138-277 H
(CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO 4-(4-CF.sub.3-Ph)--Ph O
138-278 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
4-(3-Me-Pyr-6)-Ph O 138-279 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 4-(3-Et-Pyr-6)-Ph O 138-280 H (CH.sub.2).sub.2 H H
CH.sub.2 4-tBu--PhO 4-(3-EtO-Pyr-6)-Ph O 138-281 H (CH.sub.2).sub.2
H H CH.sub.2 4-tBu--PhO 2-(4-Me--Ph)-5-Pyr O 138-282 H
(CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O
138-283 H (CH.sub.2).sub.2 H H CH.sub.2 4-tBu--PhO
2-(4-Cl--Ph)-5-Pyr O 138-284 H (CH.sub.2).sub.2 H H CH.sub.2
4-tBu--PhO 2-(4-Dma-Ph)-5-Pyr O 138-285 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3--PhO 4-(4-Me--Ph)--Ph O 138-286 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 4-(4-Dma-Ph)--Ph O
138-287 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO
4-(4-CF.sub.3-Ph)--Ph O 138-288 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 4-(3-Me-Pyr-6)-Ph O 138-289 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3--PhO 4-(3-Et-Pyr-6)-Ph O 138-290 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 4-(3-EtO-Pyr-6)-Ph O
138-291 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO
2-(4-Me--Ph)-5-Pyr O 138-292 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 138-293 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO 2-(4-Cl--Ph)-5-Pyr O
138-294 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3--PhO
2-(4-Dma-Ph)-5-Pyr O 138-295 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 4-(4-Me--Ph)--Ph O 138-296 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3O--PhO 4-(4-Dma-Ph)--Ph O 138-297 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
4-(4-CF.sub.3-Ph)--Ph O 138-298 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 4-(3-Me-Pyr-6)-Ph O 138-299 H (CH.sub.2).sub.2 H H
CH.sub.2 4-CF.sub.3O--PhO 4-(3-Et-Pyr-6)-Ph O 138-300 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 4-(3-EtO-Pyr-6)-Ph O
138-301 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
2-(4-Me--Ph)-5-Pyr O 138-302 H (CH.sub.2).sub.2 H H CH.sub.2
4-CF.sub.3O--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 138-303 H
(CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO 2-(4-Cl--Ph)-5-Pyr O
138-304 H (CH.sub.2).sub.2 H H CH.sub.2 4-CF.sub.3O--PhO
2-(4-Dma-Ph)-5-Pyr O 138-305 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-Me--Ph)--Ph O 138-306 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-Dma-Ph)--Ph O 138-307 H (CH.sub.2).sub.2 H H CH.sub.2
4-F--PhO 4-(4-CF.sub.3--Ph)--Ph O 138-308 H (CH.sub.2).sub.2 H H
CH.sub.2 4-F--PhO 4-(3-Me-Pyr-6)-Ph O 138-309 H (CH.sub.2).sub.2 H
H CH.sub.2 4-F--PhO 4-(3-Et-Pyr-6)-Ph O 138-310 H (CH.sub.2).sub.2
H H CH.sub.2 4-F--PhO 4-(3-EtO-Pyr-6)-Ph O 138-311 H
(CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-(4-Me--Ph)-5-Pyr O 138-312
H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O
138-313 H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO 2-(4-Cl--Ph)-5-Pyr
O 138-314 H (CH.sub.2).sub.2 H H CH.sub.2 4-F--PhO
2-(4-Dma-Ph)-5-Pyr O 138-315 H (CH.sub.2).sub.2 H H CH.sub.2
4-Cl--PhO 4-(4-Me--Ph)--Ph O 138-316 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Cl--PhO 4-(4-Dma-Ph)--Ph O 138-317 H (CH.sub.2).sub.2 H
H CH.sub.2 4-Cl--PhO 4-(4-CF.sub.3--Ph)--Ph O 138-318 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(3-Me-Pyr-6)-Ph O 138-319
H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 4-(3-Et-Pyr-6)-Ph O
138-320 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO
4-(3-EtO-Pyr-6)-Ph O 138-321 H (CH.sub.2).sub.2 H H CH.sub.2
4-Cl--PhO 2-(4-Me--Ph)-5-Pyr O 138-322 H (CH.sub.2).sub.2 H H
CH.sub.2 4-Cl--PhO 2-(4-CF.sub.3--Ph)-5-Py- r O 138-323 H
(CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO 2-(4-Cl--Ph)-5-Pyr O
138-324 H (CH.sub.2).sub.2 H H CH.sub.2 4-Cl--PhO
2-(4-Dma-Ph)-5-Pyr O 138-325 H (CH.sub.2).sub.2 H H CH.sub.2
3-F--PhO 4-(4-Me--Ph)--Ph O 138-326 H (CH.sub.2).sub.2 H H CH.sub.2
3-F--PhO 4-(4-Dma-Ph)--Ph O 138-327 H (CH.sub.2).sub.2 H H CH.sub.2
3-F--PhO 4-(4-CF.sub.3--Ph)--Ph O 138-328 H (CH.sub.2).sub.2 H H
CH.sub.2 3-F--PhO 4-(3-Me-Pyr-6)-Ph O 138-329 H (CH.sub.2).sub.2 H
H CH.sub.2 3-F--PhO 4-(3-Et-Pyr-6)-Ph O 138-330 H (CH.sub.2).sub.2
H H CH.sub.2 3-F--PhO 4-(3-EtO-Pyr-6)-Ph O 138-331 H
(CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 2-(4-Me--Ph)-5-Pyr O 138-332
H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O
138-333 H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO 2-(4-Cl--Ph)-5-Pyr
O 138-334 H (CH.sub.2).sub.2 H H CH.sub.2 3-F--PhO
2-(4-Dma-Ph)-5-Pyr O
[0400]
137TABLE 139 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
139-1 H (CH.sub.2).sub.2 Cl H CH.sub.2 Ph(OCH.sub.2).sub.3
4-(Pyr-2)-Ph O 139-2 H (CH.sub.2).sub.2 Cl H CH.sub.2 EtO 4-Ph--Ph
O 139-3 H (CH.sub.2).sub.2 Cl H CH.sub.2 EtO 4-(Pyr-2)-Ph O 139-4 H
(CH.sub.2).sub.2 Cl H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 139-5 H
(CH2)2 Cl H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 139-6 H
(CH.sub.2).sub.2 Cl H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O 139-7 H
(CH.sub.2).sub.2 Cl H CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O 139-8 H
(CH.sub.2).sub.2 Cl H CH.sub.2 EtO 2-TfpO-5-Pyr O 139-9 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 4-Ph--Ph O 139-10 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 4-(Pyr-2)-Ph O 139-11 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 139-12 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 139-13 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 139-14 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 139-15 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Pr 2-TfpO-5-Pyr O 139-16 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 4-Ph--Ph O 139-17 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 4-(Pyr-2)-Ph O 139-18 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 139-19 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 139-20 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 139-21 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 139-22 H
(CH.sub.2).sub.2 Cl H CH.sub.2 Bu 2-TfpO-5-Pyr O 139-23 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 4-Ph--Ph O 139-24 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 4-(Pyr-2)-Ph O 139-25 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 139-26 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 139-27 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 139-28 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 139-29 H
(CH.sub.2).sub.2 Cl H CH.sub.2 PhO 2-TfpO-5-Pyr O 139-30 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 139-31 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 139-32 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O
139-33 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-iPr--PhO
4-(3-Dma-Pyr-6)-Ph O 139-34 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 139-35 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-iPr--PhO 2-(4-MeO--Ph)-5-Pyr O 139-36 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 139-37 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 139-38 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 139-39 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 139-40 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph O 139-41 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O
139-42 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-MeO--PhO
2-(4-MeO--Ph)-5-Pyr O 139-43 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-MeO--PhO 2-TfpO-5-Pyr O 139-44 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Me--PhO 4-Ph--Ph O 139-45 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Me--PhO 4-(Pyr-2)-Ph O 139-46 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Me--PhO 4-(3-MeO-Pyr-6)-Ph O 139-47 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 139-48 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-Me--PhO 2-(4-F--Ph)-5-Pyr O 139-49 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-Me--PhO 2-(4-MeO--Ph)-5-Pyr O
139-50 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-Me--PhO 2-TfpO-5-Pyr O
139-51 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-tBu--PhO 4-Ph--Ph O
139-52 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-tBu--PhO 4-(Pyr-2)-Ph O
139-53 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-tBu--PhO
4-(3-MeO-Pyr-6)-Ph O 139-54 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 139-55 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr O 139-56 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-tBu--PhO 2-(4-MeO--Ph)-5-Pyr O 139-57 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-tBu--PhO 2-TfpO-5-Pyr O 139-58 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O 139-59 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-2)-Ph O
139-60 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3--PhO
4-(3-MeO-Pyr-6)-Ph O 139-61 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 139-62 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 139-63 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3--PhO 2-(4-MeO--Ph)-5-Pyr
O 139-64 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3--PhO
2-TfpO-5-Pyr O 139-65 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-CF.sub.3O--PhO 4-Ph--Ph O 139-66 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 139-67 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph O 139-68 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3O--PhO 4-(3-Dma-Pyr-6)-Ph
O 139-69 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-CF.sub.3O--PhO
2-(4-F--Ph)-5-Pyr O 139-70 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-CF.sub.3O--PhO 2-(4-MeO--Ph)-5-Pyr O 139-71 H (CH.sub.2).sub.2 Cl
H CH.sub.2 4-CF.sub.3O--PhO 2-TfpO-5-Pyr O 139-72 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO 4-Ph--Ph O 139-73 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO 4-(Pyr-2)-Ph O 139-74 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 139-75
H (CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O
139-76 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr
O 139-77 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-F--PhO
2-(4-MeO--Ph)-5-Pyr O 139-78 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-F--PhO 2-TfpO-5-Pyr O 139-79 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Cl--PhO 4-Ph--Ph O 139-80 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Cl--PhO 4-(Pyr-2)-Ph O 139-81 H (CH.sub.2).sub.2 Cl H CH.sub.2
4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 139-82 H (CH.sub.2).sub.2 Cl H
CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O 139-83 H (CH.sub.2).sub.2
Cl H CH.sub.2 4-Cl--PhO 2-(4-F--Ph)-5-Pyr O 139-84 H
(CH.sub.2).sub.2 Cl H CH.sub.2 4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O
139-85 H (CH.sub.2).sub.2 Cl H CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O
139-86 H (CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO 4-Ph--Ph O 139-87
H (CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 139-88 H
(CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 139-89
H (CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O
139-90 H (CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr
O 139-91 H (CH.sub.2).sub.2 Cl H CH.sub.2 3-F--PhO
2-(4-MeO--Ph)-5-Pyr O 139-92 H (CH.sub.2).sub.2 Cl H CH.sub.2
3-F--PhO 2-TfpO-5-Pyr O
[0401]
138TABLE 140 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
140-1 H (CH.sub.2).sub.2 MeO H CH.sub.2 PhO 4-(Pyr-2)-Ph O 140-2 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 4-(Pyr-2)-Ph O 140-3 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 4-Ph--Ph O 140-4 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 4-(Pyr-2)-Ph O 140-5 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 140-6 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 140-7 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O 140-8 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O 140-9 H
(CH.sub.2).sub.2 MeO H CH.sub.2 EtO 2-TfpO-5-Pyr O 140-10 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 4-Ph--Ph O 140-11 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 4-(Pyr-2)-Ph O 140-12 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 140-13 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 140-14 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 140-15 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 140-16 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Pr 2-TfpO-5-Pyr O 140-17 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 4-Ph--Ph O 140-18 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 4-(Pyr-2)-Ph O 140-19 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 140-20 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 140-21 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 140-22 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 140-23 H
(CH.sub.2).sub.2 MeO H CH.sub.2 Bu 2-TfpO-5-Pyr O 140-24 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 4-Ph--Ph O 140-25 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 140-26 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 140-27 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 140-28 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 140-29 H
(CH.sub.2).sub.2 MeO H CH.sub.2 PhO 2-TfpO-5-Pyr O 140-30 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 140-31 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 140-32 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O
140-33 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-iPr--PhO
4-(3-Dma-Pyr-6)-Ph O 140-34 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 140-35 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-iPr--PhO 2-(4-MeO--Ph)-5-Pyr O 140-36 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 140-37 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 140-38 H (CH.sub.2).sub.2 MeO
H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 140-39 H (CH.sub.2).sub.2 MeO
H CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 140-40 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph O
140-41 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-MeO--PhO
2-(4-F--Ph)-5-Pyr O 140-42 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-MeO--PhO 2-(4-MeO--Ph)-5-Pyr O 140-43 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-MeO--PhO 2-TfpO-5-Pyr O 140-44 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-Me--PhO 4-Ph--Ph O 140-45 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-Me--PhO 4-(Pyr-2)-Ph O 140-46 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-Me--PhO 4-(3-MeO-Pyr-6)-Ph O 140-47 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 140-48 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-Me--PhO 2-(4-F--Ph)-5-Pyr O
140-49 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-Me--PhO
2-(4-MeO--Ph)-5-Pyr O 140-50 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-Me--PhO 2-TfpO-5-Pyr O 140-51 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-tBu--PhO 4-Ph--Ph O 140-52 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-tBu--PhO 4-(Pyr-2)-Ph O 140-53 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-tBu--PhO 4-(3-MeO-Pyr-6)-Ph O 140-54 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 140-55 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr O 140-56 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-tBu--PhO 2-(4-MeO--Ph)-5-Pyr O
140-57 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-tBu--PhO 2-TfpO-5-Pyr O
140-58 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O
140-59 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3--PhO
4-(Pyr-2)-Ph O 140-60 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-CF.sub.3--PhO 4-(3-MeO-Pyr-6)-Ph O 140-61 H (CH.sub.2).sub.2 MeO
H CH.sub.2 4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 140-62 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O
140-63 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3--PhO
2-(4-MeO--Ph)-5-Pyr O 140-64 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-CF.sub.3--PhO 2-TfpO-5-Pyr O 140-65 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-CF.sub.3O--PhO 4-Ph--Ph O 140-66 H (CH.sub.2).sub.2 MeO
H CH.sub.2 4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 140-67 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph
O 140-68 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3O--PhO
4-(3-Dma-Pyr-6)-Ph O 140-69 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-CF.sub.3O--PhO 2-(4-F--Ph)-5-Pyr O 140-70 H (CH.sub.2).sub.2 MeO
H CH.sub.2 4-CF.sub.3O--PhO 2-(4-MeO--Ph)-5-Pyr O 140-71 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-CF.sub.3O--PhO 2-TfpO-5-Pyr O
140-72 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-F--PhO 4-Ph--Ph O 140-73
H (CH.sub.2).sub.2 MeO H CH.sub.2 4-F--PhO 4-(Pyr-2)-Ph O 140-74 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-F--PhO 4-(3-MeO-Pyr-6)-Ph O
140-75 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-F--PhO
4-(3-Dma-Pyr-6)-Ph O 140-76 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-F--PhO 2-(4-F--Ph)-5-Pyr O 140-77 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-F--PhO 2-(4-MeO--Ph)-5-Pyr O 140-78 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-F--PhO 2-TfpO-5-Pyr O 140-79 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-Cl--PhO 4-Ph--Ph O 140-80 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-Cl--PhO 4-(Pyr-2)-Ph O 140-81 H (CH.sub.2).sub.2 MeO H
CH.sub.2 4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 140-82 H (CH.sub.2).sub.2
MeO H CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O 140-83 H
(CH.sub.2).sub.2 MeO H CH.sub.2 4-Cl--PhO 2-(4-F--Ph)-5-Pyr O
140-84 H (CH.sub.2).sub.2 MeO H CH.sub.2 4-Cl--PhO
2-(4-MeO--Ph)-5-Pyr O 140-85 H (CH.sub.2).sub.2 MeO H CH.sub.2
4-Cl--PhO 2-TfpO-5-Pyr O 140-86 H (CH.sub.2).sub.2 MeO H CH.sub.2
3-F--PhO 4-Ph--Ph O 140-87 H (CH.sub.2).sub.2 MeO H CH.sub.2
3-F--PhO 4-(Pyr-2)-Ph O 140-88 H (CH.sub.2).sub.2 MeO H CH.sub.2
3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 140-89 H (CH.sub.2).sub.2 MeO H
CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O 140-90 H (CH.sub.2).sub.2
MeO H CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr O 140-91 H
(CH.sub.2).sub.2 MeO H CH.sub.2 3-F--PhO 2-(4-MeO--Ph)-5-Pyr O
140-92 H (CH.sub.2).sub.2 MeO H CH.sub.2 3-F--PhO 2-TfpO-5-Pyr
O
[0402]
139TABLE 141 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
141-1 H (CH.sub.2).sub.2 Br H CH.sub.2 EtO 4-Ph--Ph O 141-2 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 4-(Pyr-2)-Ph O 141-3 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 141-4 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 141-5 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O 141-6 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O 141-7 H
(CH.sub.2).sub.2 Br H CH.sub.2 EtO 2-TfpO-5-Pyr O 141-8 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 4-Ph--Ph O 141-9 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 4-(Pyr-2)-Ph O 141-10 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 141-11 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 141-12 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 141-13 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 141-14 H
(CH.sub.2).sub.2 Br H CH.sub.2 Pr 2-TfpO-5-Pyr O 141-15 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 4-Ph--Ph O 141-16 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 4-(Pyr-2)-Ph O 141-17 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 141-18 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 141-19 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 141-20 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 141-21 H
(CH.sub.2).sub.2 Br H CH.sub.2 Bu 2-TfpO-5-Pyr O 141-22 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 4-Ph--Ph O 141-23 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 4-(Pyr-2)-Ph O 141-24 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 141-25 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 141-26 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 141-27 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 141-28 H
(CH.sub.2).sub.2 Br H CH.sub.2 PhO 2-TfpO-5-Pyr O 141-29 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 141-30 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 141-31 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O
141-32 H (CH.sub.2).sub.2 Br H CH.sub.2 4-iPr--PhO
4-(3-Dma-Pyr-6)-Ph O 141-33 H (CH.sub.2).sub.2 Br H CH.sub.2
4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 141-34 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-iPr--PhO 2-(4-MeO--Ph)-5-Pyr O 141-35 H (CH.sub.2).sub.2
Br H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 141-36 H (CH.sub.2).sub.2
Br H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 141-37 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 141-38 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 141-39 H (CH.sub.2).sub.2
Br H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph O 141-40 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O
141-41 H (CH.sub.2).sub.2 Br H CH.sub.2 4-MeO--PhO
2-(4-MeO--Ph)-5-Pyr O 141-42 H (CH.sub.2).sub.2 Br H CH.sub.2
4-MeO--PhO 2-TfpO-5-Pyr O 141-43 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Me--PhO 4-Ph--Ph O 141-44 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Me--PhO 4-(Pyr-2)-Ph O 141-45 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Me--PhO 4-(3-MeO-Pyr-6)-Ph O 141-46 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 141-47 H (CH.sub.2).sub.2
Br H CH.sub.2 4-Me--PhO 2-(4-F--Ph)-5-Pyr O 141-48 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-Me--PhO 2-(4-MeO--Ph)-5-Pyr O
141-49 H (CH.sub.2).sub.2 Br H CH.sub.2 4-Me--PhO 2-TfpO-5-Pyr O
141-50 H (CH.sub.2).sub.2 Br H CH.sub.2 4-tBu--PhO 4-Ph--Ph O
141-51 H (CH.sub.2).sub.2 Br H CH.sub.2 4-tBu--PhO 4-(Pyr-2)-Ph O
141-52 H (CH.sub.2).sub.2 Br H CH.sub.2 4-tBu--PhO
4-(3-MeO-Pyr-6)-Ph O 141-53 H (CH.sub.2).sub.2 Br H CH.sub.2
4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 141-54 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr O 141-55 H (CH.sub.2).sub.2
Br H CH.sub.2 4-tBu--PhO 2-(4-MeO--Ph)-5-Pyr O 141-56 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-tBu--PhO 2-TfpO-5-Pyr O 141-57 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O 141-58 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-2)-Ph O
141-59 H (CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3--PhO
4-(3-MeO-Pyr-6)-Ph O 141-60 H (CH.sub.2).sub.2 Br H CH.sub.2
4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 141-61 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 141-62 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3--PhO 2-(4-MeO--Ph)-5-Pyr
O 141-63 H (CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3--PhO
2-TfpO-5-Pyr O 141-64 H (CH.sub.2).sub.2 Br H CH.sub.2
4-CF.sub.3O--PhO 4-Ph--Ph O 141-65 H (CH.sub.2).sub.2 Br H CH.sub.2
4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 141-66 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph O 141-67 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3O--PhO 4-(3-Dma-Pyr-6)-Ph
O 141-68 H (CH.sub.2).sub.2 Br H CH.sub.2 4-CF.sub.3O--PhO
2-(4-F--Ph)-5-Pyr O 141-69 H (CH.sub.2).sub.2 Br H CH.sub.2
4-CF.sub.3O--PhO 2-(4-MeO--Ph)-5-Pyr O 141-70 H (CH.sub.2).sub.2 Br
H CH.sub.2 4-CF.sub.3O---PhO 2-TfpO-5-Pyr O 141-71 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO 4-Ph--Ph O 141-72 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO 4-(Pyr-2)-Ph O 141-73 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 141-74
H (CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O
141-75 H (CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr
O 141-76 H (CH.sub.2).sub.2 Br H CH.sub.2 4-F--PhO
2-(4-MeO--Ph)-5-Pyr O 141-77 H (CH.sub.2).sub.2 Br H CH.sub.2
4-F--PhO 2-TfpO-5-Pyr O 141-78 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Cl--PhO 4-Ph--Ph O 141-79 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Cl--PhO 4-(Pyr-2)-Ph O 141-80 H (CH.sub.2).sub.2 Br H CH.sub.2
4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 141-81 H (CH.sub.2).sub.2 Br H
CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O 141-82 H (CH.sub.2).sub.2
Br H CH.sub.2 4-Cl--PhO 2-(4-F--Ph)-5-Pyr O 141-83 H
(CH.sub.2).sub.2 Br H CH.sub.2 4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O
141-84 H (CH.sub.2).sub.2 Br H CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O
141-85 H (CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO 4-Ph--Ph O 141-86
H (CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 141-87 H
(CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 141-88
H (CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O
141-89 H (CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr
O 141-90 H (CH.sub.2).sub.2 Br H CH.sub.2 3-F--PhO
2-(4-MeO--Ph)-5-Pyr O 141-91 H (CH.sub.2).sub.2 Br H CH.sub.2
3-F--PhO 2-TfpO-5-Pyr O
[0403]
140TABLE 142 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
142-1 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO 4-Ph--Ph O 142-2 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO 4-(Pyr-2)-Ph O 142-3 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 142-4
H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O
142-5 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr
O 142-6 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 EtO
2-(4-MeO--Ph)-5-Pyr O 142-7 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
EtO 2-TfpO-5-Pyr O 142-8 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Pr
4-Ph--Ph O 142-9 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Pr
4-(Pyr-2)-Ph O 142-10 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Pr
4-(3-MeO-Pyr-6)-Ph O 142-11 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
Pr 4-(3-Dma-Pyr-6)-Ph O 142-12 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 142-13 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 142-14 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 Pr 2-TfpO-5-Pyr O 142-15 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 Bu 4-Ph--Ph O 142-16 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 Bu 4-(Pyr-2)-Ph O 142-17 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 142-18 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 142-19
H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O
142-20 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 Bu
2-(4-MeO--Ph)-5-Pyr O 142-21 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
Bu 2-TfpO-5-Pyr O 142-22 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 PhO
4-Ph--Ph O 142-23 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 PhO
4-(Pyr-2)-Ph O 142-24 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 PhO
4-(3-MeO-Pyr-6)-Ph O 142-25 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
PhO 4-(3-Dma-Pyr-6)-Ph O 142-26 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 142-27 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 142-28 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 PhO 2-TfpO-5-Pyr O 142-29 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 142-30 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 142-31 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph
O 142-32 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-iPr--PhO
4-(3-Dma-Pyr-6)-Ph O 142-33 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 142-34 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-iPr--PhO 2-(4-MeO--Ph)-5-Pyr O 142-35 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 142-36 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 142-37 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O
142-38 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-MeO--PhO
4-(3-MeO-Pyr-6)-Ph O 142-39 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph O 142-40 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O 142-41 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-MeO--PhO 2-(4-MeO--Ph)-5-Pyr O 142-42 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-MeO--PhO 2-TfpO-5-Pyr O
142-43 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Me--PhO 4-Ph--Ph O
142-44 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Me--PhO
4-(Pyr-2)-Ph O 142-45 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-Me--PhO 4-(3-MeO-Pyr-6)-Ph O 142-46 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 142-47 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-Me--PhO 2-(4-F--Ph)-5-Pyr O 142-48 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Me--PhO 2-(4-MeO--Ph)-5-Pyr
O 142-49 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Me--PhO
2-TfpO-5-Pyr O 142-50 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-tBu--PhO 4-Ph--Ph O 142-51 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-tBu--PhO 4-(Pyr-2)-Ph O 142-52 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-tBu--PhO 4-(3-MeO-Pyr-6)-Ph O 142-53 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 142-54 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr O
142-55 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-tBu--PhO
2-(4-MeO--Ph)-5-Pyr O 142-56 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-tBu--PhO 2-TfpO-5-Pyr O 142-57 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O 142-58 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-2)-Ph O 142-59 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-CF.sub.3--PhO
4-(3-MeO-Pyr-6)-Ph O 142-60 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 142-61 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 142-62 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-CF.sub.3--PhO
2-(4-MeO--Ph)-5-Pyr O 142-63 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-CF.sub.3--PhO 2-TfpO-5-Pyr O 142-64 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-CF.sub.3O--PhO 4-Ph--Ph O 142-65 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 142-66 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-CF.sub.3O--PhO
4-(3-MeO-Pyr-6)-Ph O 142-67 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-CF.sub.3O--PhO 4-(3-Dma-Pyr-6)-Ph O 142-68 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-CF.sub.3O--PhO 2-(4-F--Ph)-5-Pyr O 142-69 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-CF.sub.3O--PhO
2-(4-MeO--Ph)-5-Pyr O 142-70 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-CF.sub.3O--PhO 2-TfpO-5-Pyr O 142-71 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 4-F--PhO 4-Ph--Ph O 142-72 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-F--PhO 4-(Pyr-2)-Ph O 142-73 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 142-74 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O 142-75 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr O
142-76 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-F--PhO
2-(4-MeO--Ph)-5-Pyr O 142-77 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-F--PhO 2-TfpO-5-Pyr O 142-78 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-Cl--PhO 4-Ph--Ph O 142-79 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 4-Cl--PhO 4-(Pyr-2)-Ph O 142-80 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 142-81 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O
142-82 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 4-Cl--PhO
2-(4-F--Ph)-5-Pyr O 142-83 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O 142-84 H (CH.sub.2).sub.2 NO.sub.2
H CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O 142-85 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 3-F--PhO 4-Ph--Ph O 142-86 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 142-87 H
(CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O
142-88 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2 3-F--PhO
4-(3-Dma-Pyr-6)-Ph O 142-89 H (CH.sub.2).sub.2 NO.sub.2 H CH.sub.2
3-F--PhO 2-(4-F--Ph)-5-Pyr O 142-90 H (CH.sub.2).sub.2 NO.sub.2 H
CH.sub.2 3-F--PhO 2-(4-MeO--Ph)-5-Pyr O 142-91 H (CH.sub.2).sub.2
NO.sub.2 H CH.sub.2 3-F--PhO 2-TfpO-5-Pyr O
[0404]
141TABLE 143 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
143-1 H (CH.sub.2).sub.2 Ac H CH.sub.2 EtO 4-Ph--Ph O 143-2 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 4-(Pyr-2)-Ph O 143-3 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 4-(3-MeO-Pyr-6)-Ph O 143-4 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 4-(3-Dma-Pyr-6)-Ph O 143-5 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 2-(4-F--Ph)-5-Pyr O 143-6 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 2-(4-MeO--Ph)-5-Pyr O 143-7 H
(CH.sub.2).sub.2 Ac H CH.sub.2 EtO 2-TfpO-5-Pyr O 143-8 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 4-Ph--Ph O 143-9 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 4-(Pyr-2)-Ph O 143-10 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 4-(3-MeO-Pyr-6)-Ph O 143-11 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 4-(3-Dma-Pyr-6)-Ph O 143-12 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 2-(4-F--Ph)-5-Pyr O 143-13 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 2-(4-MeO--Ph)-5-Pyr O 143-14 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Pr 2-TfpO-5-Pyr O 143-15 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 4-Ph--Ph O 143-16 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 4-(Pyr-2)-Ph O 143-17 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 4-(3-MeO-Pyr-6)-Ph O 143-18 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 4-(3-Dma-Pyr-6)-Ph O 143-19 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 2-(4-F--Ph)-5-Pyr O 143-20 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 2-(4-MeO--Ph)-5-Pyr O 143-21 H
(CH.sub.2).sub.2 Ac H CH.sub.2 Bu 2-TfpO-5-Pyr O 143-22 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 4-Ph--Ph O 143-23 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 4-(Pyr-2)-Ph O 143-24 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 4-(3-MeO-Pyr-6)-Ph O 143-25 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 4-(3-Dma-Pyr-6)-Ph O 143-26 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 2-(4-F--Ph)-5-Pyr O 143-27 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 2-(4-MeO--Ph)-5-Pyr O 143-28 H
(CH.sub.2).sub.2 Ac H CH.sub.2 PhO 2-TfpO-5-Pyr O 143-29 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-iPr--PhO 4-Ph--Ph O 143-30 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-iPr--PhO 4-(Pyr-2)-Ph O 143-31 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-iPr--PhO 4-(3-MeO-Pyr-6)-Ph O
143-32 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-iPr--PhO
4-(3-Dma-Pyr-6)-Ph O 143-33 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-iPr--PhO 2-(4-F--Ph)-5-Pyr O 143-34 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-iPr--PhO 2-(4-MeO--Ph)-5-Pyr O 143-35 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-iPr--PhO 2-TfpO-5-Pyr O 143-36 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-MeO--PhO 4-Ph--Ph O 143-37 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-MeO--PhO 4-(Pyr-2)-Ph O 143-38 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-MeO--PhO 4-(3-MeO-Pyr-6)-Ph O 143-39 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-MeO--PhO 4-(3-Dma-Pyr-6)-Ph O 143-40 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-MeO--PhO 2-(4-F--Ph)-5-Pyr O
143-41 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-MeO--PhO
2-(4-MeO--Ph)-5-Pyr O 143-42 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-MeO--PhO 2-TfpO-5-Pyr O 143-43 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Me--PhO 4-Ph--Ph O 143-44 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Me--PhO 4-(Pyr-2)-Ph O 143-45 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Me--PhO 4-(3-MeO-Pyr-6)-Ph O 143-46 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-Me--PhO 4-(3-Dma-Pyr-6)-Ph O 143-47 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-Me--PhO 2-(4-F--Ph)-5-Pyr O 143-48 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-Me--PhO 2-(4-MeO--Ph)-5-Pyr O
143-49 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-Me--PhO 2-TfpO-5-Pyr O
143-50 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-tBu--PhO 4-Ph--Ph O
143-51 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-tBu--PhO 4-(Pyr-2)-Ph O
143-52 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-tBu--PhO
4-(3-MeO-Pyr-6)-Ph O 143-53 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 143-54 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-tBu--PhO 2-(4-F--Ph)-5-Pyr O 143-55 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-tBu--PhO 2-(4-MeO--Ph)-5-Pyr O 143-56 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-tBu--PhO 2-TfpO-5-Pyr O 143-57 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O 143-58 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-2)-Ph O
143-59 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3--PhO
4-(3-MeO-Pyr-6)-Ph O 143-60 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 143-61 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 143-62 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3--PhO 2-(4-MeO--Ph)-5-Pyr
O 143-63 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3--PhO
2-TfpO-5-Pyr O 143-64 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-CF.sub.3O--PhO 4-Ph--Ph O 143-65 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 143-66 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph O 143-67 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3O--PhO 4-(3-Dma-Pyr-6)-Ph
O 143-68 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-CF.sub.3O--PhO
2-(4-F--Ph)-5-Pyr O 143-69 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-CF.sub.3O--PhO 2-(4-MeO--Ph)-5-Pyr O 143-70 H (CH.sub.2).sub.2 Ac
H CH.sub.2 4-CF.sub.3O--PhO 2-TfpO-5-Pyr O 143-71 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO 4-Ph--Ph O 143-72 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO 4-(Pyr-2)-Ph O 143-73 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 143-74
H (CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O
143-75 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr
O 143-76 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-F--PhO
2-(4-MeO--Ph)-5-Pyr O 143-77 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-F--PhO 2-TfpO-5-Pyr O 143-78 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Cl--PhO 4-Ph--Ph O 143-79 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Cl--PhO 4-(Pyr-2)-Ph O 143-80 H (CH.sub.2).sub.2 Ac H CH.sub.2
4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 143-81 H (CH.sub.2).sub.2 Ac H
CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O 143-82 H (CH.sub.2).sub.2
Ac H CH.sub.2 4-Cl--PhO 2-(4-F--Ph)-5-Pyr O 143-83 H
(CH.sub.2).sub.2 Ac H CH.sub.2 4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O
143-84 H (CH.sub.2).sub.2 Ac H CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O
143-85 H (CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO 4-Ph--Ph O 143-86
H (CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 143-87 H
(CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 143-88
H (CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O
143-89 H (CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr
O 143-90 H (CH.sub.2).sub.2 Ac H CH.sub.2 3-F--PhO
2-(4-MeO--Ph)-5-Pyr O 143-91 H (CH.sub.2).sub.2 Ac H CH.sub.2
3-F--PhO 2-TfpO-5-Pyr O
[0405]
142TABLE 144 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
144-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeNH Ph O 144-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeNH 4-Ph--Ph O 144-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeNH 4-(Pyr-2)-Ph O 144-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeNH 4-(Pyr-3)-Ph O 144-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeNH 4-(Pyr-4)-Ph O 144-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtNH Ph O 144-7 H (CH.sub.2).sub.2 H
H CH.sub.2 EtNH 4-Ph--Ph O 144-8 H (CH.sub.2).sub.2 H H CH.sub.2
EtNH 4-(Pyr-2)-Ph O 144-9 H (CH.sub.2).sub.2 H H CH.sub.2 EtNH
4-(Pyr-3)-Ph O 144-10 H (CH.sub.2).sub.2 H H CH.sub.2 EtNH
4-(Pyr-4)-Ph O 144-11 H (CH.sub.2).sub.2 H H CH.sub.2 PrNH Ph O
144-12 H (CH.sub.2).sub.2 H H CH.sub.2 PrNH 4-Ph--Ph O 144-13 H
(CH.sub.2).sub.2 H H CH.sub.2 PrNH 4-(Pyr-2)-Ph O 144-14 H
(CH.sub.2).sub.2 H H CH.sub.2 PrNH 4-(Pyr-3)-Ph O 144-15 H
(CH.sub.2).sub.2 H H CH.sub.2 PrNH 4-(Pyr-4)-Ph O 144-16 H
(CH.sub.2).sub.2 H H CH.sub.2 BuNH Ph O 144-17 H (CH.sub.2).sub.2 H
H CH.sub.2 BuNH 4-Ph--Ph O 144-18 H (CH.sub.2).sub.2 H H CH.sub.2
BuNH 4-(Pyr-2)-Ph O 144-19 H (CH.sub.2).sub.2 H H CH.sub.2 BuNH
4-(Pyr-3)-Ph O 144-20 H (CH.sub.2).sub.2 H H CH.sub.2 BuNH
4-(Pyr-4)-Ph O 144-21 H (CH.sub.2).sub.2 H H CH.sub.2 Me.sub.2N Ph
O 144-22 H (CH.sub.2).sub.2 H H CH.sub.2 Me.sub.2N 4-Ph--Ph O
144-23 H (CH.sub.2).sub.2 H H CH.sub.2 Me.sub.2N 4-(Pyr-2)-Ph O
144-24 H (CH.sub.2).sub.2 H H CH.sub.2 Me.sub.2N 4-(Pyr-3)-Ph O
144-25 H (CH.sub.2).sub.2 H H CH.sub.2 Me.sub.2N 4-(Pyr-4)-Ph O
144-26 H (CH.sub.2).sub.2 H H CH.sub.2 Et.sub.2N Ph O 144-27 H
(CH.sub.2).sub.2 H H CH.sub.2 Et.sub.2N 4-Ph--Ph O 144-28 H
(CH.sub.2).sub.2 H H CH.sub.2 Et.sub.2N 4-(Pyr-2)-Ph O 144-29 H
(CH.sub.2).sub.2 H H CH.sub.2 Et.sub.2N 4-(Pyr-3)-Ph O 144-30 H
(CH.sub.2).sub.2 H H CH.sub.2 Et.sub.2N 4-(Pyr-4)-Ph O 144-31 H
(CH.sub.2).sub.2 H H CH.sub.2 EtPhN Ph O 144-32 H (CH.sub.2).sub.2
H H CH.sub.2 EtPhN 4-Ph--Ph O 144-33 H (CH.sub.2).sub.2 H H
CH.sub.2 EtPhN 4-(Pyr-2)-Ph O 144-34 H (CH.sub.2).sub.2 H H
CH.sub.2 EtPhN 4-(Pyr-3)-Ph O 144-35 H (CH.sub.2).sub.2 H H
CH.sub.2 EtPhN 4-(Pyr-4)-Ph O 144-36 H (CH.sub.2).sub.2 H H
CH.sub.2 1-Pyrr Ph O 144-37 H (CH.sub.2).sub.2 H H CH.sub.2 1-Pyrr
4-Ph--Ph O 144-38 H (CH.sub.2).sub.2 H H CH.sub.2 1-Pyrr
4-(Pyr-2)-Ph O 144-39 H (CH.sub.2).sub.2 H H CH.sub.2 1-Pyrr
4-(Pyr-3)-Ph O 144-40 H (CH.sub.2).sub.2 H H CH.sub.2 1-Pyrr
4-(Pyr-4)-Ph O 144-41 H (CH.sub.2).sub.2 H H CH.sub.2
2-(PhSO.sub.2)--PhNH Ph O 144-42 H (CH.sub.2).sub.2 H H CH.sub.2
2-(PhSO.sub.2)--PhNH 4-Ph--Ph O 144-43 H (CH.sub.2).sub.2 H H
CH.sub.2 2-(PhSO.sub.2)--PhNH 4-(Pyr-2)-Ph O 144-44 H
(CH.sub.2).sub.2 H H CH.sub.2 2-(PhSO.sub.2)--PhNH 4-(Pyr-3)-Ph O
144-45 H (CH.sub.2).sub.2 H H CH.sub.2 2-(PhSO.sub.2)--PhNH
4-(Pyr-4)-Ph O 144-46 H (CH.sub.2).sub.2 H H CH.sub.2
4-(PhSO.sub.2)--PhNH Ph O 144-47 H (CH.sub.2).sub.2 H H CH.sub.2
4-(PhSO.sub.2)--PhNH 4-Ph--Ph O 144-48 H (CH.sub.2).sub.2 H H
CH.sub.2 4-(PhSO.sub.2)--PhNH 4-(Pyr-2)-Ph O 144-49 H
(CH.sub.2).sub.2 H H CH.sub.2 4-(PhSO.sub.2)--PhNH 4-(Pyr-3)-Ph O
144-50 H (CH.sub.2).sub.2 H H CH.sub.2 4-(PhSO.sub.2)--PhNH
4-(Pyr-4)-Ph O 144-51 H (CH.sub.2).sub.2 H H CH.sub.2
2-(PhSO.sub.2NH)--PhNH Ph O 144-52 H (CH.sub.2).sub.2 H H CH.sub.2
2-(PhSO.sub.2NH)--PhNH 4-Ph--Ph O 144-53 H (CH.sub.2).sub.2 H H
CH.sub.2 2-(PhSO.sub.2NH)--PhNH 4-(Pyr-2)-Ph O 144-54 H
(CH.sub.2).sub.2 H H CH.sub.2 2-(PhSO.sub.2NH)--PhNH 4-(Pyr-3)-Ph O
144-55 H (CH.sub.2).sub.2 H H CH.sub.2 2-(PhSO.sub.2NH)--PhNH
4-(Pyr-4)-Ph O 144-56 H (CH.sub.2).sub.2 H H CH.sub.2
4-(PhSO.sub.2NH)--PhNH Ph O 144-57 H (CH.sub.2).sub.2 H H CH.sub.2
4-(PhSO.sub.2NH)--PhNH 4-Ph--Ph O 144-58 H (CH.sub.2).sub.2 H H
CH.sub.2 4-(PhSO.sub.2NH)--PhNH 4-(Pyr-2)-Ph O 144-59 H
(CH.sub.2).sub.2 H H CH.sub.2 4-(PhSO.sub.2NH)--PhNH 4-(Pyr-3)-Ph O
144-60 H (CH.sub.2).sub.2 H H CH.sub.2 4-(PhSO.sub.2NH)--PhNH
4-(Pyr-4)-Ph O 144-61 H (CH.sub.2).sub.2 H H CH.sub.2 BzCO.sub.2NH
Ph O 144-62 H (CH.sub.2).sub.2 H H CH.sub.2 BzCO.sub.2NH 4-Ph--Ph O
144-63 H (CH.sub.2).sub.2 H H CH.sub.2 BzCO.sub.2NH 4-(Pyr-2)-Ph O
144-64 H (CH.sub.2).sub.2 H H CH.sub.2 BzCO.sub.2NH 4-(Pyr-3)-Ph O
144-65 H (CH.sub.2).sub.2 H H CH.sub.2 BzCO.sub.2NH 4-(Pyr-4)-Ph O
144-66 H (CH.sub.2).sub.2 H H CH.sub.2 PhNH Ph O 144-67 H
(CH.sub.2).sub.2 H H CH.sub.2 PhNH 4-Ph--Ph O 144-68 H
(CH.sub.2).sub.2 H H CH.sub.2 PhNH 4-(Pyr-2)-Ph O 144-69 H
(CH.sub.2).sub.2 H H CH.sub.2 PhNH 4-(Pyr-3)-Ph O 144-70 H
(CH.sub.2).sub.2 H H CH.sub.2 PhNH 4-(Pyr-4)-Ph O
[0406]
143TABLE 145 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
145-1 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-Ph--Ph O 145-2
H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-(4-HO--Ph)--Ph O
145-3 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-(4-MeO--Ph)--Ph
O 145-4 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-(4-F--Ph)--Ph
O 145-5 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO
4-(4-Cl--Ph)--Ph O 145-6 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(Pyr-2)-Ph O 145-7 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(Pyr-3)-Ph O 145-8 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(Pyr-4)-Ph O 145-9 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(3-MeO-Pyr-6)-Ph O 145-10 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-tBu--PhO 4-(3-Dma-Pyr-6)-Ph O 145-11 H (CH.sub.2).sub.2
H Me CH.sub.2 4-tBu--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-12 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
145-13 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 2-Ph-5-Pyr O
145-14 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO
2-(4-F--Ph)-5-Pyr O 145-15 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 2-(4-MeO--Ph)-5-Pyr O 145-16 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-tBu--PhO 2-TfpO-5-Pyr O 145-17 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-Ph--Ph O 145-18 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-(4-HO--Ph)--Ph O 145-19 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO 4-(4-MeO--Ph)--Ph O
145-20 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
4-(4-F--Ph)--Ph O 145-21 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 4-(4-Cl--Ph)--Ph O 145-22 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-2)-Ph O 145-23 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-3)-Ph O 145-24 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO 4-(Pyr-4)-Ph O
145-25 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
4-(3-MeO-Pyr-6)-Ph O 145-26 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 4-(3-Dma-Pyr-6)-Ph O 145-27 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-28 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-29 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 2-Ph-5-Pyr O 145-30 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 2-(4-F--Ph)-5-Pyr O 145-31 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO 2-(4-MeO--Ph)-5-Pyr
O 145-32 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
2-TfpO-5-Pyr O 145-33 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-Ph--Ph O 145-34 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-(4-HO--Ph)--Ph O 145-35 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3O--PhO 4-(4-MeO--Ph)--Ph O 145-36 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO 4-(4-F--Ph)--Ph O
145-37 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
4-(4-Cl--Ph)--Ph O 145-38 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-(Pyr-2)-Ph O 145-39 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3O--PhO 4-(Pyr-3)-Ph O 145-40 H (CH.sub.2).sub.2
H Me CH.sub.2 4-CF.sub.3O--PhO 4-(Pyr-4)-Ph O 145-41 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO 4-(3-MeO-Pyr-6)-Ph
O 145-42 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
4-(3-Dma-Pyr-6)-Ph O 145-43 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-44 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-45 H (CH.sub.2).sub.2 H Me ch.sub.2
4-CF.sub.3O--PhO 2-Ph-5-Pyr O 145-46 H (CH.sub.2).sub.2 H Me
ch.sub.2 4-CF.sub.3O--PhO 2-(4-F--Ph)-5-Pyr O 145-47 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO 2-(4-MeO--Ph)-5-Pyr
O 145-48 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
2-TfpO-5-Pyr O 145-49 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
4-Ph--Ph O 145-50 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
4-(4-HO--Ph)--Ph O 145-51 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
4-(4-MeO--Ph)--Ph O 145-52 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(4-F--Ph)--Ph O 145-53 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(4-Cl--Ph)--Ph O 145-54 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(Pyr-2)-Ph O 145-55 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(Pyr-3)-Ph O 145-56 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(Pyr-4)-Ph O 145-57 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(3-MeO-Pyr-6)-Ph O 145-58 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-F--PhO 4-(3-Dma-Pyr-6)-Ph O 145-59 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-60 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
145-61 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 2-Ph-5-Pyr O
145-62 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 2-(4-F--Ph)-5-Pyr
O 145-63 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
2-(4-MeO--Ph)-5-Pyr O 145-64 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 2-TfpO-5-Pyr O 145-65 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 4-Ph--Ph O 145-66 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 4-(4-HO--Ph)--Ph O 145-67 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 4-(4-MeO--Ph)--Ph O 145-68 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-Cl--PhO 4-(4-F--Ph)--Ph O 145-69 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-Cl--PhO 4-(4-Cl--Ph)--Ph O 145-70 H (CH.sub.2).sub.2
H Me CH.sub.2 4-Cl--PhO 4-(Pyr-2)-Ph O 145-71 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-Cl--PhO 4-(Pyr-3)-Ph O 145-72 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 4-(Pyr-4)-Ph O 145-73 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 4-(3-MeO-Pyr-6)-Ph O 145-74 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-Cl--PhO 4-(3-Dma-Pyr-6)-Ph O 145-75 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O
145-76 H (CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-77 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 2-Ph-5-Pyr O 145-78 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 2-(4-F--Ph)-5-Pyr O 145-79 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 2-(4-MeO--Ph)-5-Pyr O 145-80 H (CH.sub.2).sub.2
H Me CH.sub.2 4-Cl--PhO 2-TfpO-5-Pyr O 145-81 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-F--PhO 4-Ph--Ph O 145-82 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-F--PhO 4-(4-HO--Ph)--Ph O 145-83 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-F--PhO 4-(4-MeO--Ph)--Ph O 145-84 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-F--PhO 4-(4-F--Ph)--Ph O 145-85 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-F--PhO 4-(4-Cl--Ph)--Ph O 145-86 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-F--PhO 4-(Pyr-2)-Ph O 145-87 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-F--PhO 4-(Pyr-3)-Ph O 145-88 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-F--PhO 4-(Pyr-4)-Ph O 145-89 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-F--PhO 4-(3-MeO-Pyr-6)-Ph O 145-90 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-F--PhO 4-(3-Dma-Pyr-6)-Ph O 145-91 H (CH.sub.2).sub.2
H Me CH.sub.2 3-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-92 H
(CH.sub.2).sub.2 H Me ch.sub.2 3-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O
145-93 H (CH.sub.2).sub.2 H Me CH.sub.2 3-F--PhO 2-Ph-5-Pyr O
145-94 H (CH.sub.2).sub.2 H Me CH.sub.2 3-F--PhO 2-(4-F--Ph)-5-Pyr
O 145-95 H (CH.sub.2).sub.2 H Me CH.sub.2 3-F--PhO
2-(4-MeO--Ph)-5-Pyr O 145-96 H (CH.sub.2).sub.2 H Me CH.sub.2
3-F--PhO 2-TfpO-5-Pyr O 145-97 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CN--PhO 4-Ph--Ph O 145-98 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CN--PhO 4-(4-HO--Ph)--Ph O 145-99 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CN--PhO 4-(4-MeO--Ph)--Ph O 145-100 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-CN--PhO 4-(4-F--Ph)--Ph O 145-101 H (CH.sub.2).sub.2
H Me CH.sub.2 4-CN--PhO 4-(4-Cl--Ph)--Ph O 145-102 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 4-(Pyr-2)-Ph O 145-103 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 4-(Pyr-3)-Ph O 145-104 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 4-(Pyr-4)-Ph O 145-105 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 4-(3-MeO-Pyr-6)-Ph O
145-106 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO
4-(3-Dma-Pyr-6)-Ph O 145-107 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CN--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-108 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CN--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-109 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 2-Ph-5-Pyr O 145-110 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO 2-(4-F--Ph)-5-Pyr O
145-111 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CN--PhO
2-(4-MeO--Ph)-5-Pyr O 145-112 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CN--PhO 2-TfpO-5-Pyr O 145-113 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeS--PhO 4-Ph--Ph O 145-114 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeS--PhO 4-(4-HO--Ph)--Ph O 145-115 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeS--PhO 4-(4-MeO--Ph)--Ph O 145-116 H (CH.sub.2).sub.2
H Me CH.sub.2 4-MeS--PhO 4-(4-F--Ph)--Ph O 145-117 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 4-(4-Cl--Ph)--Ph O
145-118 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 4-(Pyr-2)-Ph O
145-119 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 4-(Pyr-3)-Ph O
145-120 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 4-(Pyr-4)-Ph O
145-121 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO
4-(3-MeO-Pyr-6)-Ph O 145-122 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeS--PhO 4-(3-Dma-Pyr-6)-Ph O 145-123 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeS--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-124 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 4-(3-0.sub.2N-Pyr-6)-Ph O
145-125 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO 2-Ph-5-Pyr O
145-126 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeS--PhO
2-(4-F--Ph)-5-Pyr O 145-127 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeS--PhO 2-(4-MeO--Ph)-5-Pyr O 145-128 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeS--PhO 2-TfpO-5-Pyr O 145-129 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeSO.sub.2--PhO 4-Ph--Ph O 145-130 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeSO.sub.2--PhO 4-(4-HO--Ph)--Ph O 145-131 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO 4-(4-MeO--Ph)--Ph
O 145-132 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO
4-(4-F--Ph)--Ph O 145-133 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeSO2--PhO 4-(4-Cl--Ph)--Ph O 145-134 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-MeSO.sub.2--PhO 4-(Pyr-2)-Ph O 145-135 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO 4-(Pyr-3)-Ph O
145-136 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO
4-(Pyr-4)-Ph O 145-137 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeSO.sub.2--PhO 4-(3-MeO-Pyr-6)-Ph O 145-138 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-MeSO.sub.2--PhO 4-(3-Dma-Pyr-6)-Ph O 145-139 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 145-140 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeSO.sub.2--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-141 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO 2-Ph-5-Pyr O
145-142 H (CH.sub.2).sub.2 H Me CH.sub.2 4-MeSO.sub.2--PhO
2-(4-F--Ph)-5-Pyr O 145-143 H (CH.sub.2).sub.2 H Me CH.sub.2
4-MeSO.sub.2--PhO 2-(4-MeO--Ph)-5-Pyr O 145-144 H (CH.sub.2).sub.2
H Me CH.sub.2 4-MeSO.sub.2--PhO 2-TfpO-5-Pyr O 145-145 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 4-Ph--Ph O 145-146 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 4-(4-HO--Ph)--Ph O
145-147 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO
4-(4-MeO--Ph)--Ph O 145-145 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4-di-F--PhO 4-(4-F--Ph)--Ph O 145-149 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,4-di-F--PhO 4-(4-Cl--Ph)--Ph O 145-150 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 4-(Pyr-2)-Ph O 145-151
H (CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 4-(Pyr-3)-Ph O
145-152 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 4-(Pyr-4)-Ph
O 145-153 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO
4-(3-MeO-Pyr-6)-Ph O 145-154 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4-di-F--PhO 4-(3-Dma-Pyr-6)-Ph O 145-155 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,4-di-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-156 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-157 H (CH.sub.2).sub.2 H Me ch.sub.2
3,4-di-F--PhO 2-Ph-5-Pyr O 145-158 H (CH.sub.2).sub.2 H Me ch.sub.2
3,4-di-F--PhO 2-(4-F--Ph)-5-Pyr O 145-159 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,4-di-F--PhO 2-(4-MeO--Ph)-5-Pyr O 145-160 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4-di-F--PhO 2-TfpO-5-Pyr O 145-161
H (CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 4-Ph--Ph O 145-162 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 4-(4-HO--Ph)--Ph O
145-163 H (CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO
4-(4-MeO--Ph)--Ph O 145-164 H (CH.sub.2).sub.2 H Me CH.sub.2
3,5-di-F--PhO 4-(4-F--Ph)--Ph O 145-165 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,5-di-F--PhO 4-(4-Cl--Ph)--Ph O 145-166 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 4-(Pyr-2)-Ph O 145-167
H (CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 4-(Pyr-3)-Ph O
145-168 H (CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 4-(Pyr-4)-Ph
O 145-169 H (CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO
4-(3-MeO-Pyr-6)-Ph O 145-170 H (CH.sub.2).sub.2 H Me CH.sub.2
3,5-di-F--PhO 4-(3-Dma-Pyr-6)-Ph O 145-171 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,5-di-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-172 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-173 H (CH.sub.2).sub.2 H Me CH.sub.2
3,5-di-F--PhO 2-Ph-5-Pyr O 145-174 H (CH.sub.2).sub.2 H Me CH.sub.2
3,5-di-F--PhO 2-(4-F--Ph)-5-Pyr O 145-175 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,5-di-F--PhO 2-(4-MeO--Ph)-5-Pyr O 145-176 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,5-di-F--PhO 2-TfpO-5-Pyr O 145-177
H (CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO 4-Ph--Ph O
145-178 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO
4-(4-HO--Ph)--Ph O 145-179 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4,5-tri-F--PhO 4-(4-MeO--Ph)--Ph O 145-180 H (CH.sub.2).sub.2 H
Me CH.sub.2 3,4,5-tri-F--PhO 4-(4-F--Ph)--Ph O 145-181 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO 4-(4-Cl--Ph)--Ph O
145-182 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO
4-(Pyr-2)-Ph O 145-183 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4,5-tri-F--PhO 4-(Pyr-3)-Ph O 145-184 H (CH.sub.2).sub.2 H Me
CH.sub.2 3,4,5-tri-F--PhO 4-(Pyr-4)-Ph O 145-185 H (CH.sub.2).sub.2
H Me CH.sub.2 3,4,5-tri-F--PhO 4-(3-MeO-Pyr-6)-Ph O 145-186 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO 4-(3-Dma-Pyr-6)-Ph
O 145-187 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 145-188 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4,5-tri-F--PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-189 H
(CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO 2-Ph-5-Pyr O
145-190 H (CH.sub.2).sub.2 H Me CH.sub.2 3,4,5-tri-F--PhO
2-(4-F--Ph)-5-Pyr O 145-191 H (CH.sub.2).sub.2 H Me CH.sub.2
3,4,5-tri-F--PhO 2-(4-MeO--Ph)-5-Pyr O 145-192 H (CH.sub.2).sub.2 H
Me CH.sub.2 3,4,5-tri-F--PhO 2-TfpO-5-Pyr O 145-193 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO 4-Ph--Ph O
145-194 H (CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(4-HO--Ph)--Ph O 145-195 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(4-MeO--Ph)--Ph O 145-196 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(4-F--Ph)--Ph O 145-197 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(4-Cl--Ph)--Ph O 145-198 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(Pyr-2)-Ph
O 145-199 H (CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(Pyr-3)-Ph O 145-200 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(Pyr-4)-Ph O 145-201 H (CH.sub.2).sub.2 H
Me CH.sub.2 2,3,4,5,6-penta-F--PhO 4-(3-MeO-Pyr-6)-Ph O 145-202 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(3-Dma-Pyr-6)-Ph O 145-203 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 4-(3-CF.sub.3-Pyr-6)-Ph O 145-204 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
4-(3-O.sub.2N-Pyr-6)-Ph O 145-205 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 2-Ph-5-Pyr O 145-206 H (CH.sub.2).sub.2 H Me
CH.sub.2 2,3,4,5,6-penta-F--PhO 2-(4-F--Ph)-5-Pyr O 145-207 H
(CH.sub.2).sub.2 H Me CH.sub.2 2,3,4,5,6-penta-F--PhO
2-(4-MeO--Ph)-5-Pyr O 145-208 H (CH.sub.2).sub.2 H Me CH.sub.2
2,3,4,5,6-penta-F--PhO 2-TfpO-5-Pyr O 145-209 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-PyrO 4-Ph--Ph O 145-210 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(4-HO--Ph)--Ph O 145-211 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(4-MeO--Ph)--Ph O 145-212 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(4-F--Ph)--Ph O 145-213 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(4-Cl--Ph)--Ph O 145-214 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(Pyr-2)-Ph O 145-215 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(Pyr-3)-Ph O 145-216 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(Pyr-4)-Ph O 145-217 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 4-(3-MeO-Pyr-6)-Ph O 145-218 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-PyrO 4-(3-Dma-Pyr-6)-Ph O
145-219 H (CH.sub.2).sub.2 H Me CH.sub.2 3-PyrO
4-(3-CF.sub.3-Pyr-6)-Ph O 145-220 H (CH.sub.2).sub.2 H Me CH.sub.2
3-PyrO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-221 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 2-Ph-5-Pyr O 145-222 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 2-(4-F--Ph)-5-Pyr O 145-223 H (CH.sub.2).sub.2 H Me
CH.sub.2 3-PyrO 2-(4-MeO--Ph)-5-Pyr O 145-224 H (CH.sub.2).sub.2 H
Me CH.sub.2 3-PyrO 2-TfpO-5-Pyr O 145-225 H (CH.sub.2).sub.2 H Me
CH.sub.2 BzO 4-Ph--Ph O 145-226 H (CH.sub.2).sub.2 H Me CH.sub.2
BzO 4-(4-HO--Ph)--Ph O 145-227 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(4-MeO--Ph)--Ph O 145-228 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(4-F--Ph)--Ph O 145-229 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(4-Cl--Ph)--Ph O 145-230 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(Pyr-2)-Ph O 145-231 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(Pyr-3)-Ph O 145-232 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(Pyr-4)-Ph O 145-233 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(3-MeO-Pyr-6)-Ph O 145-234 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(3-Dma-Pyr-6)-Ph O 145-235 H (CH.sub.2).sub.2 H Me CH.sub.2 BzO
4-(3-CF.sub.3-Pyr-6)-Ph O 145-236 H (CH.sub.2).sub.2 H Me CH.sub.2
BzO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-237 H (CH.sub.2).sub.2 H Me
CH.sub.2 BzO 2-Ph-5-Pyr O 145-238 H (CH.sub.2).sub.2 H Me CH.sub.2
BzO 2-(4-F--Ph)-5-Pyr O 145-239 H (CH.sub.2).sub.2 H Me CH.sub.2
BzO 2-(4-MeO--Ph)-5-Pyr O 145-240 H (CH.sub.2).sub.2 H Me CH.sub.2
BzO 2-TfpO-5-Pyr O 145-241 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS
4-Ph--Ph O 145-242 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS
4-(4-HO--Ph)--Ph O 145-243 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS
4-(4-MeO--Ph)--Ph O 145-244 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(4-F--Ph)--Ph O 145-245 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(4-Cl--Ph)--Ph O 145-246 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(Pyr-2)-Ph O 145-247 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(Pyr-3)-Ph O 145-248 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(Pyr-4)-Ph O 145-249 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 4-(3-MeO-Pyr-6)-Ph O 145-250 H (CH.sub.2).sub.2 H Me
CH.sub.2 2-BoxaS 4-(3-Dma-Pyr-6)-Ph O 145-251 H (CH.sub.2).sub.2 H
Me CH.sub.2 2-BoxaS 4-(3-CF.sub.3-Pyr-6)-Ph O 145-252 H
(CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS 4-(3-O.sub.2N-Pyr-6)-Ph O
145-253 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS 2-Ph-5-Pyr O
145-254 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS 2-(4-F--Ph)-5-Pyr
O 145-255 H (CH.sub.2).sub.2 H Me CH.sub.2 2-BoxaS
2-(4-MeO--Ph)-5-Pyr O 145-256 H (CH.sub.2).sub.2 H Me CH.sub.2
2-BoxaS 2-TfpO-5-Pyr O 145-257 H (CH.sub.2).sub.2 H Me CH.sub.2
4-(Pyr-2)-PhO 4-Ph--Ph O 145-258 H (CH.sub.2).sub.2 H Me CH.sub.2
4-(Pyr-2)-PhO 4-(4-HO--Ph)--Ph O 145-259 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-(Pyr-2)-PhO 4-(4-MeO--Ph)--Ph O 145-260 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO 4-(4-F--Ph)--Ph O
145-261 H (CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO
4-(4-Cl--Ph)--Ph O 145-262 H (CH.sub.2).sub.2 H Me CH.sub.2
4-(Pyr-2)-PhO 4-(Pyr-2)-Ph O 145-263 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-(Pyr-2)-PhO 4-(Pyr-3)-Ph O 145-264 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-(Pyr-2)-PhO 4-(Pyr-4)-Ph O 145-265 H (CH.sub.2).sub.2
H Me CH.sub.2 4-(Pyr-2)-PhO 4-(3-MeO-Pyr-6)-Ph O 145-266 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO 4-(3-Dma-Pyr-6)-Ph O
145-267 H (CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO
4-(3-CF.sub.3-Pyr-6)-Ph O 145-268 H (CH.sub.2).sub.2 H Me CH.sub.2
4-(Pyr-2)-PhO 4-(3-O.sub.2N-Pyr-6)-Ph O 145-269 H (CH.sub.2).sub.2
H Me CH.sub.2 4-(Pyr-2)-PhO 2-Ph-5-Pyr O 145-270 H (CH.sub.2).sub.2
H Me CH.sub.2 4-(Pyr-2)-PhO 2-(4-F--Ph)-5-Pyr O 145-271 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO 2-(4-MeO--Ph)-5-Pyr O
145-272 H (CH.sub.2).sub.2 H Me CH.sub.2 4-(Pyr-2)-PhO 2-TfpO-5-Pyr
O 145-273 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO
4-(4-Me--Ph)--Ph O 145-274 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(4-Dma-Ph)--Ph O 145-275 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-tBu--PhO 4-(4-CF.sub.3--Ph)--Ph O 145-276 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 4-(3-Me-Pyr-6)-Ph O
145-277 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO
4-(3-Et-Pyr-6)-Ph O 145-278 H (CH.sub.2).sub.2 H Me CH.sub.2
4-tBu--PhO 4-(3-EtO-Pyr-6)-Ph O 145-279 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-tBu--PhO 2-(4-Me--Ph)-5-Pyr O 145-280 H (CH.sub.2).sub.2
H Me CH.sub.2 4-tBu--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 145-281 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO 2-(4-Cl--Ph)-5-Pyr O
145-282 H (CH.sub.2).sub.2 H Me CH.sub.2 4-tBu--PhO
2-(4-Dma-Ph)-5-Pyr O 145-283 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 4-(4-Me--Ph)--Ph O 145-284 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-(4-Dma-Ph)--Ph O 145-285 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
4-(4-CF.sub.3--Ph)--Ph O 145-286 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 4-(3-Me-Pyr-6)-Ph O 145-287 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3--PhO 4-(3-Et-Pyr-6)-Ph O 145-288 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO 4-(3-EtO-Pyr-6)-Ph O
145-289 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
2-(4-Me--Ph)-5-Pyr O 145-290 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 145-291 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO 2-(4-Cl--Ph)-5-Pyr O
145-292 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3--PhO
2-(4-Dma-Ph)-5-Pyr O 145-293 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-(4-Me--Ph)--Ph O 145-294 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-CF.sub.3O--PhO 4-(4-Dma-Ph)--Ph O 145-295 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
4-(4-CF.sub.3--Ph)--Ph O 145-296 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 4-(3-Me-Pyr-6)-Ph O 145-297 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-CF.sub.3O--PhO 4-(3-Et-Pyr-6)-Ph O 145-298 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.30-PhO 4-(3-EtO-Pyr-6)-Ph O
145-299 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
2-(4-Me--Ph)-5-Pyr O 145-300 H (CH.sub.2).sub.2 H Me CH.sub.2
4-CF.sub.3O--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 145-301 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO 2-(4-Cl--Ph)-5-Pyr
O 145-302 H (CH.sub.2).sub.2 H Me CH.sub.2 4-CF.sub.3O--PhO
2-(4-Dma-Ph)-5-Pyr O 145-303 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 4-(4-Me--Ph)--Ph O 145-304 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-F--PhO 4-(4-Dma-Ph)--Ph O 145-305 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-F--PhO 4-(4-CF.sub.3--Ph)--Ph O 145-306 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 4-(3-Me-Pyr-6)-Ph O 145-307
H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 4-(3-Et-Pyr-6)-Ph O
145-308 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
4-(3-EtO-Pyr-6)-Ph O 145-309 H (CH.sub.2).sub.2 H Me CH.sub.2
4-F--PhO 2-(4-Me--Ph)-5-Pyr O 145-310 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-F--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 145-311 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO 2-(4-Cl--Ph)-5-Pyr O
145-312 H (CH.sub.2).sub.2 H Me CH.sub.2 4-F--PhO
2-(4-Dma-Ph)-5-Pyr O 145-313 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 4-(4-Me--Ph)--Ph O 145-314 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 4-(4-Dma-Ph)--Ph O 145-315 H (CH.sub.2).sub.2 H
Me CH.sub.2 4-Cl--PhO 4-(4-CF.sub.3--Ph)--Ph O 145-316 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO 4-(3-Me-Pyr-6)-Ph O
145-317 H (CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO
4-(3-Et-Pyr-6)-Ph O 145-318 H (CH.sub.2).sub.2 H Me CH.sub.2
4-Cl--PhO 4-(3-EtO-Pyr-6)-Ph O 145-319 H (CH.sub.2).sub.2 H Me
CH.sub.2 4-Cl--PhO 2-(4-Me--Ph)-5-Pyr O 145-320 H (CH.sub.2).sub.2
H Me CH.sub.2 4-Cl--PhO 2-(4-CF.sub.3--Ph)-5-Pyr O 145-322 H
(CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO 2-(4-Cl--Ph)-5-Pyr O
145-323 H (CH.sub.2).sub.2 H Me CH.sub.2 4-Cl--PhO
2-(4-Dma-Ph)-5-Pyr O
[0407]
144TABLE 146 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
146-1 H (CH.sub.2).sub.2 H H CH.sub.2 EtO 4-Ph-Ph O 146-2 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-2)-Ph O 146-3 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-3)-Ph O 146-4 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 4-(Pyr-4)-Ph O 146-5 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 2-Ph-5-Pyr O 146-6 H
(CH.sub.2).sub.2 H H CH.sub.2 EtO 3-Ph-6-Pyr O
[0408]
145TABLE 147 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
147-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pr 4-Ph-Ph O 147-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-2)-Ph O 147-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-3)-Ph O 147-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 4-(Pyr-4)-Ph O 147-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 2-Ph-5-Pyr O 147-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pr 3-Ph-6-Pyr O
[0409]
146TABLE 148 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
148-1 H (CH.sub.2).sub.2 H H CH.sub.2 Bu 4-Ph-Ph O 148-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-2)-Ph O 148-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-3)-Ph O 148-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 4-(Pyr-4)-Ph O 148-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 2-Ph-5-Pyr O 148-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Bu 3-Ph-6-Pyr O
[0410]
147TABLE 149 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
149-1 H (CH.sub.2).sub.2 H H CH.sub.2 Pen 4-Ph-Ph O 149-2 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-2)-Ph O 149-3 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-3)-Ph O 149-4 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 4-(Pyr-4)-Ph O 149-5 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 2-Ph-5-Pyr O 149-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Pen 3-Ph-6-Pyr O
[0411]
148TABLE 150 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
150-1 H (CH.sub.2).sub.2 H H CH.sub.2 MeS 4-Ph-Ph O 150-2 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-2)-Ph O 150-3 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-3)-Ph O 150-4 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 4-(Pyr-4)-Ph O 150-5 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 2-Ph-5-Pyr O 150-6 H
(CH.sub.2).sub.2 H H CH.sub.2 MeS 3-Ph-6-Pyr O
[0412]
149TABLE 151 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
151-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhO 4-Ph-Ph O 151-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-2)-Ph O 151-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-3)-Ph O 151-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 4-(Pyr-4)-Ph O 151-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 2-Ph-5-Pyr O 151-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhO 3-Ph-6-Pyr O
[0413]
150TABLE 152 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
152-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-Ph-Ph O 152-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-2)-Ph O 152-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-3)-Ph O 152-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 4-(Pyr-4)-Ph O 152-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 2-Ph-5-Pyr O 152-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-iPr-PhO 3-Ph-6-Pyr O
[0414]
151TABLE 153 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
153-1 H (CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 4-Ph-Ph O 153-2 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 4-(Pyr-2)-Ph O 153-3 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 4-(Pyr-3)-Ph O 153-4 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 4-(Pyr-4)-Ph O 153-5 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 2-Ph-5-Pyr O 153-6 H
(CH.sub.2).sub.2 H H CH.sub.2 4-MeO-PhO 3-Ph-6-Pyr O
[0415]
152TABLE 154 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
154-1 H (CH.sub.2).sub.2 H H CH.sub.2 PhS 4-Ph-Ph O 154-2 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-2)-Ph O 154-3 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-3)-Ph O 154-4 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 4-(Pyr-4)-Ph O 154-5 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 2-Ph-5-Pyr O 154-6 H
(CH.sub.2).sub.2 H H CH.sub.2 PhS 3-Ph-6-Pyr O
[0416]
153TABLE 155 Ex. No. Comp. R.sup.1 R.sup.2 R.sup.3 R.sup.4 Z W X Y
155-1 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 4-Ph-Ph O
155-2 H (CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3
4-(Pyr-2)-Ph O 155-3 H (CH.sub.2).sub.2 H H CH.sub.2
Ph(CH.sub.2).sub.3 4-(Pyr-3)-Ph O 155-4 H (CH.sub.2).sub.2 H H
CH.sub.2 Ph(CH.sub.2).sub.3 4-(Pyr-4)-Ph O 155-5 H (CH.sub.2).sub.2
H H CH.sub.2 Ph(CH.sub.2).sub.3 2-Ph-5-Pyr O 155-6 H
(CH.sub.2).sub.2 H H CH.sub.2 Ph(CH.sub.2).sub.3 3-Ph-6-Pyr O
[0417] In the above tables,
[0418] (1) the following compounds are preferred: compounds
Nos.
[0419] 1-15, 1-16, 1-17, 1-19, 1-21, 1-35, 1-37, 1-39, 1-90, 1-92,
1-93, 1-94, 1-95, 1-96, 1-97, 1-98, 1-99, 1-100, 1-101, 1-102,
1-103, 1-104, 1-105, 1-106, 1-107, 1-108, 1-109, 1-110, 1-111,
1-112, 1-143, 1-150, 1-179, 1-189, 1-190, 1-191, 1-204, 1-205,
1-206, 1-207, 1-208, 1-209, 1-210, 1-211, 1-212, 1-213, 1-214,
1-215, 1-216, 1-217, 1-218, 1-219, 1-220, 1-221, 1-222, 1-223,
1-224, 1-225, 1-226, 1-227, 1-228, 1-229, 1-230, 1-231, 1-232,
1-233, 1-234, 1-235, 1-236, 1-242, 1-243, 1-244, 1-246,
[0420] 3-15, 3-16, 3-17, 3-19, 3-21, 3-35, 3-37, 3-39, 3-90, 3-92,
3-93, 3-94, 3-95, 3-96, 3-97, 3-98, 3-99, 3-100, 3-101, 3-102,
3-103, 3-104, 3-105, 3-106, 3-107, 3-108, 3-109, 3-110, 3-111,
3-112, 3-143, 3-150, 3-179, 3-189, 3-190, 3-191, 3-204, 3-205,
3-206, 3-207, 3-208, 3-209, 3-210, 3-211, 3-212, 3-213, 3-214,
3-215, 3-216, 3-217, 3-218 3-219, 3-220, 3-221, 3-222, 3-223,
3-224, 3-225, 3-226, 3-227, 3-228, 3-229, 3-230, 3-231, 3-232,
3-233, 3-234, 3-235, 3-236, 3-242, 3-243, 3-244, 3-246,
[0421] 4-15, 4-16, 4-17, 4-19, 4-21, 4-35, 4-37, 4-39, 4-90, 4-92,
4-93, 4-94, 4-95, 4-96, 4-97, 4-98, 4-99, 4-100, 4-101, 4-102,
4-103, 4-104, 4-105, 4-106, 4-107, 4-108, 4-109, 4-110, 4-111,
4-112, 4-143, 4-150, 4-179, 4-189, 4-190, 4-191, 4-193, 4-204,
4-205, 4-206, 4-207, 4-208, 4-209, 4-210, 4-211, 4-212, 4-213,
4-214, 4-215, 4-216, 4-217, 4-218, 4-219, 4-220, 4-221, 4-222,
4-223, 4-224, 4-225, 4-226, 4-227, 4-228, 4-229, 4-230, 4-231,
4-232, 4-233, 4-234, 4-235, 4-236, 4-242, 4-243, 4-244, 4-246,
[0422] 5-15, 5-16, 5-17, 5-19, 5-21, 5-35, 5-37, 5-39, 5-90, 5-92,
5-93, 5-94, 5-95, 5-96, 5-97, 5-98, 5-99, 5-100, 5-101, 5-102,
5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5-109, 5-110, 5-111,
5-112,
[0423] 6-15, 6-16, 6-17, 6-19, 6-21, 6-35, 6-37, 6-39, 6-90, 6-92,
6-93, 6-94, 6-95, 6-96, 6-97, 6-98, 6-99, 6-100, 6-101, 6-102,
6-103, 6-104, 6-105, 6-106, 6-107, 6-108, 6-109, 6-110, 6-111,
6-112, 6-143, 6-150, 6-179, 6-189, 6-190, 6-191, 6-204, 6-205,
6-206, 6-207, 6-208, 6-209, 6-210, 6-211, 6-212, 6-213, 6-214,
6-215, 6-216, 6-217, 6-218, 6-219, 6-220, 6-221, 6-222, 6-223,
6-224, 6-225, 6-226, 6-227, 6-228, 6-229, 6-230, 6-231, 6-232,
6-233, 6-234, 6-235, 6-236, 6-242, 6-243, 6-244, 6-246,
[0424] 7-15, 7-16, 7-17, 7-19, 7-21, 7-35, 7-37, 7-39, 7-90, 7-92,
7-93, 7-94, 7-95, 7-96, 7-97, 7-98, 7-99, 7-100, 7-101, 7-102,
7-103, 7-104, 7-105, 7-106, 7-107, 7-108, 7-109, 7-110, 7-111,
7-112, 7-143, 7-150, 7-179, 7-189, 7-190, 7-191, 7-204, 7-205,
7-206, 7-207, 7-208, 7-209, 7-210, 7-211, 7-212, 7-213,
7-214,7-215, 7-216, 7-217, 7-218, 7-219, 7-220, 7-221, 7-222,
7-223, 7-224,7-225, 7-226,7-227, 7-228, 7-229, 7-230, 7-231, 7-232,
7-233, 7-234, 7-235, 7-236, 7-242, 7-243, 7-244, 7-246,
[0425] 8-15, 8-16, 8-17, 8-19, 8-21, 8-35, 8-37, 8-39, 8-90, 8-92,
8-93, 8-94, 8-95, 8-96, 8-97, 8-98, 8-99, 8-100, 8-101, 8-102,
8-103, 8-104, 8-105, 8-106, 8-107, 8-1088-109, 8-110, 8-111, 8-112,
8-143, 8-150, 8-179, 8-189, 8-190,8-191, 8-204, 8-205, 8-206,
8-207, 8-208, 8-209, 8-210, 8-211, 8-212, 8-213, 8-214, 8-215,
8-216, 8-217, 8-218, 8-219, 8-220, 8-221, 8-222, 8-223, 8-224,
8-225, 8-226, 8-227, 8-228, 8-229, 8-230, 8-231, 8-232, 8-233,
8-234, 8-235, 8-236, 8-242, 8-243, 8-244, 8-246,
[0426] 9-15, 9-16, 9-17, 9-19, 9-21, 9-35, 9-37, 9-39, 9-90, 9-92,
9-93, 9-94, 9-95, 9-96, 9-97, 9-98, 9-99, 9-100, 9-101, 9-102,
9-103, 9-104, 9-105, 9-106, 9-107, 9-108, 9-109, 9-110, 9-111,
9-112,
[0427] 10-11, 10-15, 10-16, 10-17, 10-19, 10-21, 10-35, 10-37,
10-39, 10-90, 10-92, 10-93, 10-94, 10-95, 10-96, 10-97, 10-98,
10-99, 10-100, 10-101, 10-102, 10-103, 10-104, 10-105, 10-106,
10-107, 10-108, 10-109, 10-110, 10-111, 10-112,
[0428] 11-5, 11-11, 11-12, 11-13, 11-37,
[0429] 12-5, 12-11, 12-12, 12-13, 12-37,
[0430] 13-5, 13-11, 13-12, 13-13, 13-37,
[0431] 14-5, 14-11, 14-12, 14-13, 14-37, 14-42, 14-43, 14-44,
14-45, 14-46, 14-47, 14-48, 14-49, 14-50, 14-51, 14-52, 14-53,
14-54, 14-55, 14-61, 14-62, 14-64, 14-65, 14-66, 14-67, 14-68,
14-69, 14-70, 14-73, 14-74, 14-75, 14-76, 14-77, 14-78, 14-84,
14-85, 14-86, 14-88,
[0432] 15-5, 15-11, 15-12, 15-13, 15-37, 15-42, 15-43, 15-44,
15-45, 15-46, 15-47, 15-48, 15-49, 15-50, 15-51, 15-52, 15-53,
15-54, 15-55, 15-61, 15-62, 15-64, 15-65, 15-66, 15-67, 15-68,
15-69, 15-70, 15-73, 15-74, 15-75, 15-76, 15-77, 15-78, 15-84,
15-85, 15-86, 15-88,
[0433] 16-5, 16-11, 16-12, 16-13, 16-37,
[0434] 17-5, 17-11, 17-12, 17-13, 17-37,
[0435] 18-2, 18-3, 18-4, 18-5, 18-16,
[0436] 19-2, 19-3, 19-4, 19-5, 19-16,
[0437] 20-2, 20-3, 20-4, 20-5, 20-16, 20-30, 20-33, 20-37, 20-39,
20-42, 20-52, 20-53, 20-70, 20-71, 20-79, 20-80,
[0438] 23-2, 23-3, 23-4, 23-5, 23-16,
[0439] 24-2, 24-3, 24-4, 24-5, 24-16,
[0440] 25-2, 25-3, 25-4, 25-5, 25-16,
[0441] 28-2, 28-3, 28-4, 28-5, 28-16, 28-17, 28-18, 28-19, 28-20,
28-21, 28-22, 28-23, 28-b 24, 28-25, 28-31, 28-32, 28-33, 28-34,
28-35, 28-36, 28-37, 28-38, 28-39, 28-40, 28-41, 28-42,28-43,
[0442] 29-2, 29-3, 29-4, 29-5, 29-16, 29-17, 29-18, 29-19, 29-20,
29-21, 29 -22, 29-23, 29-24, 29-25, 29-31, 29-32, 29-33, 29-34,
29-35, 29-36, 29-37, 29-38, 29-39, 29-40, 29-41, 29-42, 29-43,
[0443] 30-2, 30-3, 30-4, 30-5, 30-16, 30-17, 30-18, 30-19, 30-20,
30-21, 30-22, 30-23, 30-24, 30-25, 30-31, 30-32, 30-33, 30-34,
30-35, 30-36, 30-37, 30-38, 30-39, 30-40, 30-41, 30-42, 30-43,
[0444] 31-2, 31-3, 31-4, 31-5, 31-16, 31-17, 32-2, 32-3, 32-4,
32-5, 32-16, 32-17,
[0445] 33-2, 33-3, 33-4, 33-5, 33-16, 33-17, 33-18, 33-19, 33-20,
33-21, 33-22, 33-23, 33-24, 33-25, 33-31, 33-32, 33-33, 33-34,
33-35, 33-36, 33-37, 33-38, 33-39, 33-40, 33-41, 33-42, 33-43,
33-49, 33-50, 33-51, 33-53,
[0446] 34-2, 34-3, 34-4, 34-5, 34-16, 34-17, 34-18, 34-19, 34-20,
34-21, 34-22, 34-23, 34-24, 34-25, 34-31, 34-32, 34-33, 34-34,
34-35, 34-36, 34-37, 34-38, 34-39, 34-40, 34-41, 34-42, 34-43,
34-49, 34-50, 34-51, 34-53,
[0447] 35-2, 35-3, 35-4, 35-5, 35-16, 35-17, 35-18, 35-19, 35-20,
35-21, 35-22, 35-23, 35-24, 35-25, 35-31, 35-32, 35-33, 35-34,
35-35, 35-36, 35-37, 35-38, 35-39, 35-40, 35-41, 35-42, 35-43,
35-49, 35-50, 35-51, 35-53,
[0448] 36-2, 36-3, 36-4, 36-5, 36-16, 36-17,
[0449] 37-2, 37-3, 37-4, 37-5, 37-16, 37-17,
[0450] 38-2, 38-3, 38-4, 38-5, 38-31, 38-34, 38-38, 38-40,
38-43,
[0451] 39-2, 39-3, 39-4, 39-5, 39-31, 39-34, 39-38, 39-40,
39-43,
[0452] 40-2, 40-3, 40-4, 40-5, 40-31, 40-34, 40-38, 40-40,
40-43,
[0453] 43-2, 43-3, 43-4, 43-5, 43-31, 43-34, 43-38, 43-40,
43-43,
[0454] 44-2, 44-3, 44-4, 44-5, 44-31, 44-34, 44-38, 44-40,
44-43,
[0455] 45-2, 45-3, 45-4, 45-5, 45-31, 45-34, 45-38, 45-40,
45-43,
[0456] 58-2, 58-3, 58-4, 58-5, 58-16, 58-17,
[0457] 59-2, 59-3, 59-4, 59-5, 59-16, 59-17,
[0458] 60-2, 60-3, 60-4, 60-5, 60-16, 60-17,
[0459] 63-2, 63-3, 63-4, 63-5, 63-16, 63-17,
[0460] 64-2, 64-3, 64-4, 64-5, 64-16, 64-17,
[0461] 65-2, 65-3, 65-4, 65-5, 65-16, 65-17,
[0462] 77-2, 77-3, 77-4, 77-5,
[0463] 78-2, 78-3, 78-4, 78-5, 78-16, 78-17,
[0464] 79-2, 79-3, 79-4, 79-5, 79-16, 79-17,
[0465] 80-2, 80-3, 80-4, 80-5, 80-16, 80-17,
[0466] 83-2, 83-3, 83-4, 83-5, 83-16, 83-17,
[0467] 84-2, 84-3, 84-4, 84-5, 84-16, 84-17,
[0468] 85-2, 85-3, 85-4, 85-5, 85-16, 85-17,
[0469] 88-1, 88-2, 88-3, 88-4, 88-5, 88-6,
[0470] 89-1, 89-2, 89-3, 89-4, 89-5, 89-6,
[0471] 90-1, 90-2, 90-3, 90-4, 90-5, 90-6,
[0472] 93-1, 93-2, 93-3, 93-4, 93-5, 93-6,
[0473] 94-1, 94-2, 94-3, 94-4, 94-5, 94-6,
[0474] 95-1, 95-2, 95-3, 95-4, 95-5, 95-6,
[0475] 98-1, 98-2, 98-3, 98-4, 98-5, 98-6,
[0476] 103-1, 103-2, 103-3, 103-4, 103-5, 103-6,
[0477] 104-1, 104-2, 104-3, 104-4, 104-5, 104-6,
[0478] 105-1, 105-2, 105-3, 105-4, 105-5, 105-6,
[0479] 138-2, 138-3, 138-4, 138-5, 138-6, 138-7, 138-8, 138-9,
138-10,138-11, 138-12, 138-13, 138-14, 138-15, 138-16, 138-17,
138-18, 138-19, 138-20, 138-21, 138-22, 138-23, 138-24, 138-25,
138-26, 138-27, 138-28, 138-29, 138-30, 138-31, 138-32, 138-33,
138-34, 138-35, 138-36, 138-37, 138-38, 138-39, 138-40, 138-41,
138-42, 138-43, 138-44, 138-45, 138-46, 138-47, 138-48, 138-49,
138-50, 138-51, 138-52, 138-53, 138-54, 138-55, 138-56, 138-57,
138-58, 138-59, 138-60, 138-61, 138-62, 138-63, 138-64, 138-65,
138-66, 138-67, 138-68, 138-69, 138-70, 138-71, 138-72, 138-73,
138-74, 138-75, 138-76, 138-77, 138-78, 138-79, 138-80, 138-81,
138-82, 138-83, 138-84, 138-85, 138-86, 138-87, 138-88, 138-89,
138-90, 138-91, 138-92, 138-93, 138-94, 138-95, 138-96, 138-97,
138-98, 138-99, 138-104, 138-105, 138-106, 138-107, 138-108,
138-111, 138-112, 138-113, 138-114, 138-115, 138-120, 138-121,
138-122, 138-123, 138-124, 138-127, 138-128, 138-129, 138-130,
138-131, 138-136, 138-137, 138-138, 138-139, 138-140, 138-143,
138-144, 138-145, 138-146, 138-147, 138-152, 138-153, 138-154,
138-155, 138-156, 138-159, 138-160, 138-161, 138-162, 138-163,
138-168, 138-169, 138-170, 138-171, 138-172, 138-175, 138-176,
138-177, 138-178, 138-179, 138-184, 138-185, 138-186, 138-187,
138-188, 138-191, 138-192, 138-193, 138-194, 138-195, 138-200,
138-201, 138-202, 138-203, 138-204, 138-207, 138-208, 138-209,
138-210, 138-211, 138-216, 138-217, 138-218, 138-219, 138-220,
138-223, 138-224, 138-225, 138-226, 138-227, 138-232, 138-233,
138-234, 138-235, 138-236, 138-239, 138-240, 138-241, 138-242,
138-243, 138-248, 138-249, 138-250, 138-251, 138-252, 138-255,
138-256, 138-257, 138-258, 138-259, 138-264, 138-265, 138-266,
138-267, 138-268, 138-271, 138-272, 138-273, 138-274, 138-275,
138-285, 138-295, 138-305, 138-315, 138-325,
[0480] 139-24, 139-31,
[0481] 140-2, 140-31,
[0482] 141-23, 141-30,
[0483] 142-23, 142-30,
[0484] 143-23, 143-30,
[0485] 144-8, 144-13, 144-18, 144-28, 144-33, 144-63,
[0486] 145-1, 145-6, 145-7, 145-8, 145-9, 145-10, 145-13, 145-14,
145-15, 145-16, 145-17, 145-22, 145-23, 145-24, 145-25, 145-26,
145-29, 145-30, 145-31, 145-32, 145-33, 145-38, 145-39, 145-40,
145-41, 145-42, 145-45, 145-46, 145-47, 145-48, 145-49, 145-54,
145-55, 145-56, 145-57, 145-58, 145-61, 145-62, 145-63, 145-64,
145-65, 145-70, 145-71, 145-72, 145-73, 145-74, 145-77, 145-78,
145-79, 145-80, 145-81, 145-86, 145-87, 145-88, 145-89, 145-90,
145-93, 145-94, 145-95, 145-96, 145-97, 145-102, 145-111, 145-112,
145-118, 145-127, 145-128, 145-134, 145-143, 145-144, 145-150,
145-159, 145-160, 145-166, 145-175, 145-176, 145-182, 145-191,
145-192, 145-198, 145-207, 145-208, 145-214, 145-223, 145-224,
145-230, 145-239, 145-240, 145-246, 145-255, 145-256, 145-262,
145-271, 145-272, 145-273, 145-283, 145-293, 145-303, and
145-313;
[0487] (2) the following compounds are more preferred: compounds
Nos.
[0488] 1-15, 1-35, 1-37, 1-39, 1-95, 1-110, 1-179, 1-189, 1-190,
1-191, 1-204, 1-205, 1-206, 1-207, 1-208, 1-209, 1-210, 1-212,
1-213, 1-219, 1-222, 1-223, 1-224, 1-225, 1-226, 1-227, 1-228,
1-229, 1-230, 1-231, 1-232, 1-233, 1-234, 1-235, 1-236, 1-242,
1-243, 1-244,
[0489] 3-15, 3-35, 3-37, 3-39, 3-95, 3-110, 3-179, 3-189, 3-190,
3-191, 3-204, 3-205, 3-206, 3-207, 3-208, 3-209, 3-210, 3-212,
3-213, 3-219, 3-222, 3-223, 3-224, 3-225, 3-226, 3-227, 3-228,
3-229, 3-230, 3-231, 3-232, 3-233, 3-234, 3-235, 3-236, 3-242,
3-243,
[0490] 4-15, 4-35, 4-37, 4-39, 4-95, 4-96, 4-98, 4-106, 4-110,
4-143, 4-150, 4-179, 4-189, 4-190, 4-191, 4-193, 4-204, 4-205,
4-206, 4-207,4-208, 4-209, 4-210, 4-211, 4-212, 4-213, 4-214,
4-215, 4-216, 4-217, 4-218, 4-219, 4-220, 4-221, 4-222, 4-223,
4-224, 4-225, 4-226, 4-227, 4-228, 4-229, 4-230, 4-231, 4-232,
4-233, 4-234, 4-235, 4-236, 4-242, 4-243, 4-244,
[0491] 5-15, 5-35, 5-37, 5-39, 5-95, 5-110,
[0492] 6-15, 6-35, 6-37, 6-39, 6-95, 6-96, 6-110, 6-179, 6-189,
6-190, 6-191, 6-204, 6-205, 6-206, 6-207, 6-208, 6-209, 6-210,
6-212, 6-213, 6-219, 6-222, 6-223, 6-224, 6-225, 6-226, 6-227,
6-228, 6-229, 6-230, 6-231, 6-232, 6-233, 6-234, 6-235, 6-236,
6-242, 6-243, 6-244,
[0493] 7-15, 7-35, 7-37, 7-39, 7-95, 7-110, 7-179, 7-189, 7-190,
7-191, 7-204, 7-206, 7-207, 7-208, 7-209, 7-210, 7-212, 7-213,
7-219, 7-222, 7-223, 7-224, 7-225, 7-226, 7-227, 7-228, 7-229,
7-230, 7-231, 7-232, 7-233, 7-234, 7-235, 7-236, 7-242, 7-243,
7-244,
[0494] 8-15, 8-35, 8-37, 8-39, 8-95, 8-110, 8-179, 8-189, 8-190,
8-191, 8-204, 8-205, 8-206, 8-207, 8-208, 8-209, 8-210, 8-212,
8-213, 8-219, 8-222, 8-223, 8-224, 8-225, 8-226, 8-227, 8-228,
8-229, 8-230, 8-231, 8-232, 8-233, 8-234, 8-235, 8-236, 8-242,
8-243, 8-244,
[0495] 9-15, 9-35, 9-37, 9-39, 9-95, 9-110,
[0496] 14-5, 14-11, 14-12, 14-13, 14-37, 14-44, 14-45, 14-47,
14-64, 14-67, 14-73, 14-75, 14-78, 14-84, 14-85, 14-86,
[0497] 15-5, 15-11, 15-12, 15-13, 15-37, 15-44, 15-45, 15-47,
15-64, 15-67, 15-73, 15-75, 15-78, 15-84, 15-85, 15-86,
[0498] 17-11,
[0499] 20-53, 20-71, 20-80,
[0500] 28-2, 28-3, 28-4, 28-5, 28-16, 28-17, 28-19, 28-22, 28-31,
28-34, 28-38, 28-40, 28-43,
[0501] 30-3,
[0502] 33-2, 33-3, 33-4, 33-5, 33-16, 33-17, 33-19, 33-22, 33-31,
33-34, 33-38, 33-40, 33-43,
[0503] 33-49, 33-50, 33-51,
[0504] 34-2, 34-3, 34-4, 34-5, 34-16, 34-1734-19, 34-22, 34-31,
34-34, 34-38, 34-40, 34-43, 35-49, 35-50, 35-51, 35-2, 35-3, 35-4,
35-5, 35-16, 35-17, 35-19, 35-22, 35-31, 35-34, 35-38, 35-40,
35-43, 35-49, 35-50, 35-51,
[0505] 37-3,
[0506] 38-2, 38-3, 38-4, 38-5,
[0507] 39-2, 39-3, 39-4, 39-5,
[0508] 40-2, 40-3, 40-4, 40-5,
[0509] 43-2, 43-3, 43-4, 43-5,
[0510] 44-2, 44-3, 44-4, 44-5,
[0511] 45-2, 45-3, 45-4, 45-5,
[0512] 77-3,
[0513] 138-2, 138-3, 138-8, 138-9, 138-10, 138-11, 138-12, 138-15,
138-16, 138-17, 138-18, 138-19, 138-24, 138-25, 138-26, 138-27,
138-28, 138-31, 138-32, 138-33, 138-34, 138-35, 138-40, 138-41,
138-42, 138-43, 138-44, 138-47, 138-48, 138-49, 138-50, 138-51,
138-56, 138-57, 138-58, 138-59, 138-60, 138-63, 138-64, 138-65,
138-66, 138-67, 138-72, 138-73, 138-74, 138-75, 138-76, 138-79,
138-80, 138-81, 138-82, 138-83, 138-88, 138-89, 138-90, 138-91,
138-92, 138-95, 138-96, 138-97, 138-98, 138-104, 138-120, 138-136,
138-152, 138-168, 138-184, 138-200, 138-216, 138-232, 138-248,
138-264, 138-275, 138-285, 138-295, 138-305, 138-315, 138-325,
[0514] 139-24, 139-31,
[0515] 140-2, 140-31,
[0516] 141-23, 141-30,
[0517] 142-23, 142-30,
[0518] 143-23, 143-30,
[0519] 144-13, 144-63,
[0520] 145-6, 145-15, 145-16, 145-22, 145-31, 145-32, 145-47,
145-48, 145-54, 145-63, 145-64, 145-70, 145-79, 145-80, 145-86,
145-95, 145-96, 145-102, 145-118, 145-134, 145-150, 145-166,
145-182, 145-198, 145-214, 145-230, 145-246, 145-262, 145-273,
145-283, 145-293, 145-303 and 145-313;
[0521] (3) Much more preferred compounds are selected from the
group of the following compounds:
[0522] 1)
2-ethoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]propi-
onic acid
[0523] 2)
3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]-2-propylpropi-
onic acid
[0524] 3) 2-butyl-3- [4-
[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]prop- ionic acid
[0525] 4)
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-butylpropioni- c
acid
[0526] 5)
2-butyl-3-[4-[2-(4'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl-
]propionic acid
[0527] 6)
2-butyl-3-[4-[2-(4'-dimethylaminomethylbiphenyl-4-carbonylamino)-
ethoxy]phenyl]propionic acid
[0528] 7)
2-butyl-3-[4-[2-(4'-carboxybiphenyl-4-carbonylamino)ethoxy]pheny-
l]propionic acid
[0529] 8)
2-butyl-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy]pheny-
l]propionic acid
[0530] 9)
2-butyl-3-[4-[2-(3'-hydroxybiphenyl-4-carbonylamino)ethoxy]pheny-
l]propionic acid
[0531] 10)
2-butyl-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)ethoxy]phen-
yl]propionic acid
[0532] 11)
2-butyl-3-[4-[2-(4'-hydroxy-3,5-dimethylbiphenyl-4-carbonylamin-
o)ethoxy]phenyl]propionic acid
[0533] 12)
2-butyl-3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]pheny-
l]propionic acid
[0534] 13)
2-butyl-3-[4-[2-(4-diethylaminobenzoylamino)ethoxy]phenyl]propi-
onic acid
[0535] 14)
2-butyl-3-[4-[3-(4-pyridyl-2-ylbenzoylamino)propoxy]phenyl]prop-
ionic acid
[0536] 15)
2-phenoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionic acid
[0537] 16)
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropi-
onic acid
[0538] 17)
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phe-
noxypropionic acid
[0539] 18)
3-[4-[2-(4'-chlorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phe-
noxypropionic acid
[0540] 19)
3-[4-[2-(4'-trifluoromethylbiphenyl-4-carbonylamino)ethoxy]phen-
yl]-2-phenoxypropionic acid
[0541] 20)
2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)etho-
xy]phenyl]propionic acid
[0542] 21)
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropyl-
phenoxy)propionic acid
[0543] 22)
2-(4-isopropylphenoxy)-3-[4-[2-(2-phenylpyridine-5-carbonylamin-
o)ethoxy]phenyl]propionic acid
[0544] 23)
2-(4-isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-c-
arbonylamino)ethoxy]phenyl]propionic acid
[0545] 24)
3-[4-[2-[2-(4-fluorophenyl)pyridine-5-carbonylamino]ethoxy]phen-
yl]-2-(4-isopropylphenoxy)propionic acid
[0546] 25)
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino-
]ethoxy]phenyl]-2-(4-isopropylphenoxy)propionic acid
[0547] 26)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-trifluoromethylpyridine-6--
yl)benzoylamino]ethoxy]phenyl]propionic acid
[0548] 27)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-nitropyridine-6-yl)benzoyl-
amino]ethoxy]phenyl]propionic acid
[0549] 28)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-methoxypyridine-6-yl)benzo-
ylamino]ethoxylphenyl]propionic acid
[0550] 29)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-dimethylaminopyridine-6-yl-
)benzoylamino]ethoxy)phenyl]propionic acid
[0551] 30)
2-(4-methoxyphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy-
]phenyl]propionic acid
[0552] 31)
2-(3-phenylpropyl)-3[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]ph-
enyl]propionic acid
[0553] 32)
2-(4-methylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0554] 33)
2-(4-t-butylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy-
]phenyl]propionic acid
[0555] 34)
2-(4-fluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0556] 35)
2-(4-chlorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0557] 36)
2-(4-trifluoromethylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamin-
o)ethoxy]phenyl]-propionic acid
[0558] 37)
2-(4-trifluoromethoxyphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylami-
no)ethoxy]phenyl]propionic acid
[0559] 38) 2-(3
-fluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy-
]phenyl]propionic acid
[0560] 39)
2-(3,5-difluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)eth-
oxy]phenyl]-propionic acid
[0561] 40)
2-(3,4-difluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)eth-
oxy]phenyl]-propionic acid
[0562] 41)
2-(3,4,5-trifluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)-
ethoxy]phenyl]propionic acid
[0563] 42)
2-(2,3,4,5,6-pentafluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoyl-
amino)ethoxy]phenyl]propionic acid
[0564] 43)
2-methyl-2-phenoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]p-
henyl]propionic acid
[0565] 44)
2-(4-isopropylphenoxy)-2-methyl-3-[4-[2-(4-pyridyl-2-ylbenzoyla-
mino)ethoxy]phenyl]propionic acid
[0566] 45)
2-(4-isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-c-
arbonylamino]-ethoxy]phenyl]-2-methylpropionic acid and
[0567] 46)
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino-
]ethoxy]phenyl]-2-(4-isopropylphenoxy)-2-methylpropionic acid
[0568] and pharmaceutically acceptable salts and esters
thereof.
[0569] (4) Most preferred compounds are selected from the group of
the following compounds:
[0570] 1)
2-ethoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]propi-
onic acid
[0571] 2)
3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]-2-propylpropi-
onic acid
[0572] 3)
2-butyl-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]propio-
nic acid
[0573] 4)
2-butyl-3-[4-[2-(4'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl-
]propionic acid
[0574] 5)
2-butyl-3-[4-[2-(4'-hydroxy-3,5-dimethybiphenyl-4-carbonylamino)-
ethoxy]-phenyl]propionic acid
[0575] 6)
2-phenoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionic acid
[0576] 7)
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropio-
nic acid
[0577] 8)
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phen-
oxypropionic acid
[0578] 9)
3-[4-[2-(4'-chlorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phen-
oxypropionic acid
[0579] 10)
2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)etho-
xy]phenyl]propionic acid
[0580] 11)
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropyl-
phenoxy) propionic acid
[0581] 12)
2-(4-isopropylphenoxy)-3-[4-[2-(2-phenylpyridine-5-carbonylamin-
o)ethoxy]phenyl]propionic acid
[0582] 13)
2-(4-isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-c-
arbonylamino]ethoxy]phenyl]propionic acid
[0583] 14)
3-[4-[2-[2-(4-fluorophenyl)pyridine-5-carbonylamino]ethoxy]phen-
yl]-2-(4-isopropylphenoxy)propionic acid
[0584] 15)
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino-
]ethoxy]phenyl]-2-(4-isopropylphenoxy)propionic acid
[0585] 16)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-methoxypyridine-6-yl)-benz-
oylamino]ethoxy]phenyl]propionic acid
[0586] 17)
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-dimethylaminopyridine-6-yl-
)benzoylamino]ethoxy]phenyl]propionic acid
[0587] 18)
2-(4-methoxyphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy-
]phenyl]propionic acid
[0588] 19)
2-(4-methylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0589] 20)
2-(4-t-butylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy-
]phenyl]propionic acid
[0590] 21)
2-(4-fluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0591] 22)
2-(4-chlorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0592] 23)
2-(4-trifluoromethylphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamin-
o)ethoxy]phenyl ]propionic acid
[0593] 24)
2-(4-trifluoromethoxyphenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylami-
no)ethoxy]phenyl]propionic acid
[0594] 25)
2-(3-fluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]-
phenyl]propionic acid
[0595] 26)
2-(3,4,5-trifluorophenoxy)-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)-
ethoxy]phenyl]propionic acid
[0596] 27)
2-methyl-2-phenoxy-3-[4-[2-(4-pyridyl-2-ylbenzoylamino)ethoxy]p-
henyl]propionic acid
[0597] 28)
2-(4-isopropylphenoxy)-2-methyl-3-[4-[2-(4-pyridyl-2-yl-benzoyl-
amino)ethoxy]phenyl]propionic acid
[0598] 29)
2-(4-isopropylphenoxy)-[4-[2-[2-(4-methoxyphenyl)pyridine-5-car-
bonylamino]ethoxy]phenyl]-2-methylpropionic acid and
[0599] 30)
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino-
]ethoxy]phenyl]-2-(4-isopropylphenoxy)-2-methylpropionic acid
[0600] and pharmaceutically acceptable salts and esters
thereof.
[0601] In the nomenclature herein, reference to a
"(4-pyridyl-2-ylbenzoyla- mino)" group should have correctly named
the "(4-pyridine-2-ylbenzoylamino- )" group.
[0602] The amidocarboxylic acid derivatives of formula (I) of the
present invention, pharmacologically acceptable salts thereof or
pharmacologically acceptable esters thereof are easily prepared
according to the following method A:
[0603] <<Method A>> 5
[0604] wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, W, X, Y and Z
have the same meanings as defined above; W.sup.1 represents an
amino group protected by a conventional protecting group such as
t-butoxycarbonyl in the case where W represents a primary or
secondary amino group and W.sup.1 has the same meaning as defined
for W in the case where W.sup.1 represents other groups; and in the
case where the amidocarboxylic acid of formula (I) forms an ester,
M represents the ester residue.
[0605] Step A
[0606] Step A1 is to prepare a compound of formula (III) and the
compound is prepared by acylating a compound of formula (II).
[0607] The present reaction is a reaction for forming an amide bond
well known in organic synthetic chemistry and is preferably usually
carried out in the presence of a solvent.
[0608] The solvent employed here is not particularly limited so
long as it has no adverse effect on the reaction and includes, for
example, an inert solvent, preferably halogenated hydrocarbons such
as dichloromethane and chloroform; esters such as ethyl acetate;
ethers such as tetrahydrofuran and dioxane; and amides such as
N,N-dimethylacetamide and N,N-dimethylformamide.
[0609] The reaction is carried out by treatment with a condensation
agent.
[0610] The condensation agent employed here includes carbodiimides
such as N,N-dicyclohexylcarbodiimide and
1-(3-dimethylaminopropyl)-3-ethylcarbodi- imide hydrochloride;
phosphoryl compounds such as diphenylphosphoryl azide and
diethylphosphoryl cyanide; carbonyldiimidazole; and
triphenylphosphine-diethyl azodicarbonate; preferably
carbonyldiimidazole and carbodiimides. In the case where phosphoryl
compounds are employed, the reaction is preferably carried out in
the presence of a tertiary amine such as triethylamine and
N-methylmorpholine.
[0611] Alternatively the present reaction is accomplished by
reacting the carboxylic acid used in the present reaction or a salt
thereof with a lower alkyl ester of chloroformic acid such as ethyl
chloroformate and isobutyl chloroformate in the presence of a
tertiary amine such as triethylamine and N-methylmorpholine to form
a mixed acid anhydride or by reacting the carboxylic acid used in
the present reaction or a salt thereof with N-hydroxysuccinimide,
N-hydroxybenzotriazole or p-nitrophenol in the presence of
carbodiimides such as N,N-dicyclohexylcarbodiimide to form the
corresponding activated ester, and thereafter, by condensing these
compounds with amines.
[0612] The reaction is preferably usually carried out in the
presence of a solvent. The solvent employed here is not
particularly limited so long as it has no adverse effect on the
reaction and includes, for example, an inert solvent, preferably
halogenated hydrocarbons such as dichloromethane and chloroform;
ethers such as tetrahydrofuran and dioxane; and aromatic
hydrocarbons such as benzene and toluene.
[0613] As a further alternative, the compound is obtained by
reacting the carboxylic acid used in the present reaction or a salt
thereof with a halogenating agent, preferably phosphorus
pentachloride, oxalyl chloride or thionyl chloride to afford the
corresponding acyl halide and then by reacting the acyl halide with
amines in a similar manner to that described above.
[0614] The reaction is preferably usually carried out in the
presence of a solvent. The solvent employed here is not
particularly limited so long as it has no adverse effect on the
present reaction and includes, for example, an inert solvent,
preferably halogenated hydrocarbons such as dichloromethane; ethers
such as tetrahydrofuran and dioxane; and aromatic hydrocarbons such
as benzene and toluene.
[0615] The reaction is carried out at -20.degree. C. to 100.degree.
C., preferably at -5.degree. C. to 50.degree. C.
[0616] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to
24 hours, preferably 1 hour to 16 hours.
[0617] Step A2
[0618] Step A2 is to prepare a phenylalkylcarboxylic acid
derivative of formula (I) and is carried out by removal of an ester
residue from the compound of formula (III).
[0619] The present step is accomplished by hydrolysis with a base
in the presence of a solvent.
[0620] In the present reaction, the solvent employed here is not
particularly limited so long as it has no adverse effect on the
reaction and preferably includes, for example, ethers such as
diethyl ether, tetrahydrofuran and dioxane; alcohols such as
methanol, ethanol and methoxyethanol; water; or a mixture of these
solvents.
[0621] The base employed in the reaction includes, for example,
alkali metal hydroxides such as lithium hydroxide, sodium hydroxide
and potassium hydroxide; and alkali metal carbonates such as
lithium carbonate, sodium carbonate and potassium carbonate;
preferably the alkali metal hydroxides.
[0622] The reaction temperature varies depending on the solvent and
the base used but is 0.degree. C. to 140.degree. C., preferably
10.degree. C. to 120.degree. C.
[0623] While the reaction time varies depending on the solvent, the
base and the reaction temperature employed, it is usually 10
minutes to 24 hours, preferably 30 minutes to 16 hours.
[0624] Alternatively, in the case where the ester residue is a
t-butyl group, a diphenylmethyl group or a p-methoxybenzyl group,
the present step is carried out by reacting the ester with an
organic acid such as formic acid, acetic acid trifluoroacetic acid,
methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid
and trifluoromethanesulfonic acid or a mineral acid such as
hydrochloric acid and sulfuric acid, preferably trifluoroacetic
acid or hydrochloric acid in the presence or absence of a
solvent.
[0625] In the case where a solvent is used in the present reaction,
the solvent is not particularly limited so long as it has no
adverse effect on the reaction and includes. for example,
hydrocarbons such as benzene, toluene, xylene, hexane and heptane;
halogenated hydrocarbons such as chloroform, methylene chloride and
carbon tetrachloride; ethers such as diethyl ether, tetrahydrofuran
and dioxane; alcohols such as methanol and ethanol; amides such as
N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; esters such as methyl acetate and
ethyl acetate; water; or a mixture of these solvents; preferably
ethers.
[0626] While the reaction temperature varies depending on the acid
used, it is -10.degree. C. to 120.degree. C., preferably 0.degree.
C. to 100.degree. C.
[0627] While the reaction time varies depending on the acid used
and the reaction temperature, it is usually 10 minutes to 24 hours,
preferably 30 minutes to 16 hours.
[0628] As a further alternative, the present step is accomplished
by carrying out a catalytic hydrogenation reaction on the compound
of the formula (III) in the case where the ester residue is an
aralkyl group such as a benzyl group or a diphenylmethyl group. The
catalyst employed here includes, for example, palladium on carbon,
palladium black, platinum oxide and platinum black, preferably
palladium on carbon.
[0629] The reaction is preferably usually carried out in the
presence of a solvent. The solvent employed here is not
particularly limited so long as it has no adverse effect on the
reaction and includes, for example, hydrocarbons such as benzene,
toluene, xylene, hexane and heptane; halogenated hydrocarbons such
as chloroform, methylene chloride and carbon tetrachloride; ethers
such as diethyl ether, tetrahydrofuran and dioxane; alcohols such
as methanol, ethanol and isopropanol; amides such as
N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; carboxylic acids such as formic acid
and acetic acid; or a mixture of these solvents; preferably
alcohols.
[0630] The reaction temperature is 10.degree. C. to 140.degree. C.,
preferably 20.degree. C. to 120.degree. C.
[0631] The reaction time varies depending on the reagent, the
reaction temperature and the solvent and is usually 30 minutes to 3
days, preferably 1 hour to 24 hours.
[0632] As another alternative, in the case where W.sup.1 represents
a primary or secondary amino group protected by a conventional
protecting group such as a t-butoxycarbonyl, after the above
reaction, deprotection can be carried out according to a known
method. for example, by reacting the protected amino compound with
an acid such as hydrochloric acid at room temperature for 30
minutes to 2 hours.
[0633] In the formula (II) of Method A, the compound (IIa) in which
R.sup.1 has the hydrogen atom can be also prepared according to
Method B or Method C.
[0634] <<Method B>> 6
[0635] wherein R.sup.2, R.sup.3, R.sup.4, Y, Z, W.sup.1 and M have
the same meanings as defined above.
[0636] P represents a conventional protecting group for a hydroxyl
group such as a 2-tetrahydropyranyl group or a methoxymethyl group:
U represents a hydroxyl group, a halogen atom (preferably a
chlorine atom, a bromine atom or an iodine atom) or a group of the
formula: --O--SO.sub.2--R.sup.6 (wherein R.sup.6 represents an
alkyl group having from 1 to 6 carbon atoms such as a methyl or
ethyl group; a halogenated alkyl group having from 1 to 4 carbon
atoms such as a trifluoromethyl group; or an aryl group having from
6 to 10 carbon atoms which may have an alkyl group having from 1 to
4 carbon atoms, a nitro group or halogen atom as a substituent,
such as a phenyl, p-tolyl, p-nitrophenyl or p-bromophenyl group).
U.sup.1 represents a halogen atom or a group of formula:
--O--SO.sub.2--R.sup.6 (wherein R.sup.6 has the same meaning as
defined above for U).
[0637] Step B1
[0638] Step B1 in Method B is to prepare a compound of formula (VI)
and the compound is prepared by reacting a compound of formula (IV)
with a compound of formula (V).
[0639] In the case where U is a hydroxyl group, the reaction is
carried out according to the conventional Mitsunobu reaction [O.
Mitsunobu, Synthesis, page 1, (1981)].
[0640] The reaction is usually carried out by contacting azo
compounds with phosphines in the presence of a solvent. As the azo
compound of the reagent, C.sub.1-C.sub.4 alkyl azodicarboxylates
such as diethyl azodicarboxylate and azodicarboxamides such as
1,1'-(azodicarbonyl)dipipe- ridine are used. As the phosphines,
triarylphosphines such as triphenylphosphine and tri
(C.sub.1-C.sub.4 alkyl)phosphines such as tributylphosphine are
used.
[0641] The reaction is preferably usually carried out in the
presence of a solvent. The solvent employed here is not
particularly limited so long as it has no adverse effect on the
present reaction and includes, for example, hydrocarbons such as
benzene, toluene, xylene, hexane and heptane; halogenated
hydrocarbons such as chloroform, methylene chloride, carbon
tetrachloride and 1,2-dichloroethane; ethers such as diethyl ether,
tetrahydrofuran and dioxane; amides such as N,N-dimethylformamide,
N,N-dimethylacetamide and hexamethylphosphoric triamide; or a
mixture of these solvents; preferably the hydrocarbons, halogenated
hydrocarbons or ethers. The reaction temperature is 10.degree. C.
to 100.degree. C., preferably 20.degree. C. to 80.degree. C.
[0642] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 1 hour to 3
days, preferably 5 hours to 2 days.
[0643] In the case where U represents a halogen atom or a group of
formula: --O--SO.sub.2--R.sup.6 (wherein R.sup.6 has the same
meaning as defined above), the reaction is carried out in an inert
solvent in the presence of a base.
[0644] The base employed here preferably includes alkali metal
carbonates such as sodium carbonate and potassium carbonate; alkali
metal hydrides such as sodium hydride, potassium hydride and
lithium hydride; alkali metal alkoxides such as sodium methoxide,
sodium ethoxide, potassium t-butoxide and lithium methoxide; alkyl
lithiums such as butyl lithium and methyl lithium; lithium amides
such as lithium diethylamide, lithium diisopropylamide and lithium
bis(trimethylsilyl)amide; alkali metal hydrogencarbonates such as
sodium hydrogencarbonate and potassium hydrogencarbonate; and
tertiary organic amines such as 1,5-diazabicyclo[4.3.0]non-5-ene,
1,8-diazabicyclo[5.4.0]undec-7-ene and N,N-diisopropylethylamine;
more preferably alkali metal carbonates, alkali metal hydrides or
alkali metal alkoxides.
[0645] The inert solvent used in the reaction is not particularly
limited so long as it has no adverse effect on the reaction and
includes hydrocarbons such as benzene and toluene; ethers such as
tetrahydrofuran and dioxane; alcohols such as methanol, ethanol and
t-butanol; amides such as N,N-dimethylformamide,
N,N-dimethylacetamide and N-methylpyrrolidinone; ketones such as
acetone and 2-butanone; nitrites such as acetonitrile; sulfoxides
such as dimethyl sulfoxide; or mixtures thereof; preferably ethers,
amides, ketones or sulfoxides.
[0646] In the case where the present reaction is carried out in the
presence of a phase transfer catalyst such as
benzyltriethylammonium iodide and tetrabutylammonium iodide, alkali
metal hydroxides such as sodium hydroxide and potassium hydroxide
are used as the base and the reaction is carried out in a solvent
which is a two-layer system of water and a halogenated hydrocarbon
such as methylene chloride and chloroform.
[0647] The reaction temperature is -10.degree. C. to 120.degree.
C., preferably 10.degree. C. to 100.degree. C.
[0648] While the reaction time varies depending on the reagent used
and the reaction temperature, it is usually 30 minutes to 48 hours,
preferably 1 hour to 16 hours.
[0649] Step B2
[0650] Step B2 is to prepare a compound of formula (VII) and is
carried out by removal of the hydroxy protecting group such as a
2-tetrahydropyranyl group from the compound of the formula
(VI).
[0651] The present reaction is carried out in a similar manner to
the method of deprotection using an acid described in Step A2 of
Method A.
[0652] Step B3
[0653] Step B3 is to prepare a compound of formula (VIII) and is
carried out by converting the hydroxyl group of the compound of
formula (VII) to a halogen atom or a group of formula:
--O--SO.sub.2--R.sup.6 (wherein R.sup.6 has the same meaning as
defined above).
[0654] The halogenation is carried out by reaction of compound
(VII) with a hydrohalogenic acid such as hydrochloric acid and
hydrobromic acid; halides of inorganic acids such as thionyl
chloride, thionyl bromide, phosphorus trichloride, phosphorus
tribromide, phosphorus pentachloride and phosphorus oxychloride;
Vilsmeier reagents such as N,N-dimethylchloroforminium and
N,N-dimethylbromoforminium; or halogenation reagents containing a
phosphorus compound such as triphenylphosphine and carbon
tetrachloride or carbon tetrabromide, and triethylphosphine
dichloride and triethylphosphine dibromide in an inert solvent or
without a solvent.
[0655] The solvent employed here is not particularly limited so
long as it has no adverse effect on the reaction and includes, for
example, hydrocarbons such as benzene, toluene, xylene, hexane and
heptane; halogenated hydrocarbons such as chloroform, methylene
chloride, carbon tetrachloride and 1,2-dichloroethane; ethers such
as diethyl ether, tetrahydrofuran and dioxane; amides such as
N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; and mixtures thereof; preferably
hydrocarbons, halogenated hydrocarbons or ethers.
[0656] The reaction temperature is -50.degree. C. to 150.degree.
C., preferably 0.degree. C. to 80.degree. C.
[0657] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to 3
days, preferably 1 hour to 24 hours.
[0658] The sulfonation reaction is carried out by reaction of
compound (VII) with a reagent of formula:
R.sup.6--SO.sub.2--U.sup.2 or (R.sup.6--SO.sub.2).sub.2 (wherein
R.sup.6 has the same meaning as defined above and U.sup.2
represents a halogen atom (preferably a chlorine atom)) in an inert
solvent in the presence of a base.
[0659] The solvent employed here is not particularly limited so
long as it has no adverse effect on the present reaction and
includes, for example, hydrocarbons such as benzene, toluene,
xylene, hexane and heptane; halogenated hydrocarbons such as
chloroform, methylene chloride, carbon tetrachloride and
1,2-dichloroethane; ethers such as diethyl ether, tetrahydrofuran
and dioxane; amides such as N,N-dimethylformamide,
N,N-dimethylacetamide and hexamethylphosphoric triamide;
nitrogen-containing aromatic compounds such as pyridine and
collidine; or mixtures thereof; preferably halogenated hydrocarbons
or nitrogen-containing aromatic compounds.
[0660] The base employed here includes alkali metal carbonates such
as sodium carbonate and potassium carbaonate; alkali metal
hydrogencarbonates such as sodium hydrogencarbonate and potassium
hydrogencarbonate; or tertiary organic amines such as
triethylamine, N-methylmorpholine, N,N-diisopropylethylamine,
1,5-diazabicyclo[4.3.0]non- -5-ene and
1,8-diazabicyclo[5.4.0]undec-7-ene; preferably tertiary organic
amines.
[0661] The reaction temperature is -70.degree. C. to 100.degree.
C., preferably 0.degree. C. to 80.degree. C.
[0662] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to
48 hours, preferably 1 hour to 16 hours.
[0663] Step B4
[0664] Step B4 is to prepare a compound of formula (IX) and is
carried out by converting the halogen atom or group of formula:
--O--SO.sub.2--R.sup.6 (wherein R.sup.6 has the same meaning as
defined above) of the compound of formula (VIII) to an azide
group.
[0665] The present reaction is carried out by reacting a metal
azide such as sodium azide or an organic azide such as
tetrabutylammonium azide in an inert solvent.
[0666] The solvent employed here is not particularly limited so
long as it has no adverse effect on the present reaction and
includes, for example, hydrocarbons such as benzene, toluene,
xylene, hexane and heptane; halogenated hydrocarbons such as
chloroform, methylene chloride, carbon tetrachloride and
1,2-dichloroethane; ethers such as diethyl ether, tetrahydrofuran
and dioxane; amides such as N,N-dimethylformamide,
N,N-dimethylacetamide and hexamethylphosphoric triamide; or
mixtures thereof; preferably ethers or amides.
[0667] The reaction temperature is 0.degree. C. to 150.degree. C.,
preferably 20.degree. C. to 100.degree. C.
[0668] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 1 hour to 3
days, preferably 1 hour to 24 hours.
[0669] Step B5
[0670] Step B5 is to prepare a compound of formula (IIa) and is
carried out by converting the azide group of the compound of
formula (IX) to an amino group.
[0671] The present reaction is accomplished by carrying out a
catalytic reduction using palladium on carbon, Raney nickel,
Lindlar catalyst, etc. as a catalyst or a reduction using
triphenylphosphine, etc. in an inert solvent.
[0672] The solvent employed here is not particularly limited so
long as it has no adverse effect on the present reaction and
includes, for example, hydrocarbons such as benzene, toluene,
xylene, hexane and heptane; alcohols such as methanol and ethanol;
ethers such as diethyl ether, tetrahydrofuran and dioxane; amides
such as N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; and mixtures thereof; preferably
alcohols or ethers.
[0673] The reaction temperature is 0.degree. C. to 150.degree. C.,
preferably 20.degree. C. to 100.degree. C. While the reaction time
varies depending on the reagent, the reaction temperature and the
solvent, it is usually 1 hour to 3 days, preferably 1 hour to 24
hours.
[0674] <<Method C>> 7
[0675] wherein
[0676] R.sup.2, R.sup.3, R.sup.4, U, X, Y, W.sup.1 and M have the
same meanings as defined above;
[0677] R.sup.7 represents a hydrogen atom; R.sup.8 represents an
amino protecting group; or R.sup.7 and R.sup.8 each represent an
amino protecting group; or R.sup.7, together with R.sup.8 represent
an amino protecting group.
[0678] The amino protecting group of R.sup.7 or R.sup.8 is a
protecting group well-known in organic synthetic chemistry and
includes, for example, a C.sub.7-C.sub.14 aralkyl group such as
benzyl, diphenylmethyl and trityl; a C.sub.1-C.sub.4 aliphatic acyl
group which may be substituted with fluorine such as formyl and
trifluoroacetyl; a C.sub.1-C.sub.4 alkoxycarbonyl group such as
t-butoxycarbonyl; a benzyloxycarbonyl group which may be
substituted with methoxy or nitro such as benzyloxycarbonyl,
p-methoxybenzyloxycarbonyl or p-nitrobenzyloxycarbonyl. In the case
where R.sup.7, together with R.sup.8 represent an amino protecting
group, the protecting group includes, for example, a phthaloyl
group, etc.; preferably a t-butoxycarbonyl, benzyloxycarbonyl or
phthaloyl group.
[0679] Step C.sub.1
[0680] Step C.sub.1 is to prepare a compound of formula (XI) and is
carried out by reacting a compound of formula (X) with a compound
of formula (V).
[0681] The present step is carried out in a similar manner to that
described in Step B1 of Method B.
[0682] Step C2
[0683] Step C2 is to prepare a compound of formula (IIa) and is
carried out by removal of the amino protecting group from the
compound of formula (XI).
[0684] In the case where the protecting group R.sup.7 or R.sup.8 is
a group which can be removed by catalytic reduction such as an
aralkyl group and an aralkyloxycarbonyl group or a group which can
be removed using an acid such as a trityl group and a
t-butoxycarbonyl group, the deprotecting reation is carried out in
a similar manner to that described in Step A2 of Process A.
[0685] In the case where the protecting group R.sup.7 or R.sup.8 is
an aliphatic acyl group such as formyl and trifluoroacetyl, the
protecting group is removed under basic conditions.
[0686] The base employed here includes alkali metal hydroxides such
as sodium hydroxide, potassium hydroxide and lithium hydroxide; and
alkali metal carbonates such as sodium carbonate and potassium
carbonate; preferably alkali metal hydroxides.
[0687] The present reaction is preferably carried out in an inert
solvent, for example, alcohols such as methanol and ethanol; water;
ethers such as tetrahydrofuran and dioxane; and mixtures thereof;
more preferably alcohols.
[0688] The reaction temperature is 0.degree. C. to 100.degree. C.,
preferably 10.degree. C. to 80.degree. C.
[0689] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to
24 hours, preferably 1 hour to 16 hours.
[0690] In the case where R.sup.7, together with R.sup.8 represent
an amino protecting group and it is a phthaloyl group, the
protecting group can be removed by treating it with hydrazines or
primary amines.
[0691] The hydrazines employed here include, for example,
hydrazine, methylhydrazine and phenylhydrazine, preferably
hydrazine. The primary amines employed here includes methylamine,
ethylamine, propylamine, butylamine, isobutylamine, pentylamine and
hexylamine, preferably propylamine or butylamine.
[0692] In the present reaction an inert solvent, for example,
alcohols such as methanol and ethanol; ethers such as
tetrahydrofuran and dioxane; halogenated hydrocarbons such as
methylene chloride and chloroform; and mixtures thereof are
preferably used. The alcohols are more preferably employed.
[0693] The reaction temperature is 0.degree. C. to 100.degree. C.,
preferably 10.degree. C. to 80.degree. C.
[0694] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to
24 hours, preferably 1 hour to 16 hours.
[0695] In the formula (II) in Method A, a compound in which R.sup.1
is an alkyl group or an aralkyl group can also be prepared
according to Method D or Method E.
[0696] <<Method D>> 8
[0697] wherein R.sup.2, R.sup.3, R.sup.4, U.sup.1, Y, W.sup.1 and M
have the same meanings as defined above. R.sup.1-1 represents a
straight or branched chain alkyl group having from 1 to 6 carbon
atoms or an aralkyl group having from 7 to 12 carbon atoms.
[0698] Step D1
[0699] Step D1 is to prepare a compound of formula (IIb) and is
carried out by reacting a compound of formula (VIII) with an amine
of formula (XII).
[0700] The present reaction is carried out in an inert solvent in
the presence or absence of a base.
[0701] The solvent employed here is not particularly limited so
long as it has no adverse effect on the present reaction and
includes, for example, hydrocarbons such as benzene, toluene,
xylene, hexane and heptane; alcohols such as methanol and ethanol;
ethers such as diethyl ether, tetrahydrofuran and dioxane; amides
such as N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; or mixtures thereof; preferably
ethers or amides.
[0702] The base employed here includes alkali metal carbonates such
as sodium carbonate and potassium carbonate; alkali metal
hydrogencarbonates such as sodium hydrogencarbonate and potassium
hydrogencarbonate; and tertiary organic amines such as
triethylamine, N-methylmorpholine, N,N-diisopropylethylamine,
1,5-diazabicyclo[4.3.0]non-5-ene and
1,8-diazabicyclo[5.4.0]undec-7-ene; preferably alkali metal
carbonates or tertiary organic amines.
[0703] The reaction temperature is 0.degree. C. to 150.degree. C.,
preferably 20.degree. C. to 100.degree. C.
[0704] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 1 hour to 3
days, preferably 1 hour to 24 hours.
[0705] <<Method E>> 9
[0706] wherein
[0707] R.sup.1-1, R.sup.2, R.sup.3, R.sup.4, Y, Z, W.sup.1 and M
have the same meanings as defined above.
[0708] R.sup.9 represents a straight or branched chain alkyl group
having from 1 to 6 carbon atoms or an aralkyl group having from 7
to 12 carbon atoms and R.sup.10 represents a straight or branched
chain alkyl group having from 1 to 6 carbon atoms, an aralkyl group
having from 7 to 12 carbon atoms or a hydrogen atom.
[0709] Step E1
[0710] Step E1 is to prepare a compound of formula (IIb) and is
carried out by reacting a compound of formula (IIa) with a carbonyl
compound of formula (XIII).
[0711] The present reaction is carried out in an inert solvent
under reduction conditions using a metal hydride such as sodium
borohydride and sodium cyanoborohydride or under catalytic
reduction conditions using palladium on carbon or Raney nickel as a
catalyst.
[0712] The solvent employed here is not particularly limited so
long as it has no adverse effect on the present reaction and
includes hydrocarbons such as benzene, toluene, xylene, hexane and
heptane; alcohols such as methanol and ethanol; ethers such as
diethyl ether, tetrahydrofuran and dioxane; amides such as
N,N-dimethylformamide, N,N-dimethylacetamide and
hexamethylphosphoric triamide; or mixtures thereof; preferably
alcohols or amides.
[0713] The reaction temperature is 0.degree. C. to 150.degree. C.,
preferably 20.degree. C. to 100.degree. C.
[0714] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent it is usually 1 hour to 3
days, preferably 1 hour to 24 hours.
[0715] In the formula (III) in Method A, the compound (lIla) in
which W is an aryloxy group, a hetero aryloxy group, an arylthio
group or a hetero arylthio group can be also prepared according to
Method F.
[0716] <<Method F>> 10
[0717] wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, U, X, Y, Z and M
have the same meanings as defined above. W.sup.2 represents an
aryloxy group, an hetero aryl group, an arylthio group or an hetero
arylthio group in W described above.
[0718] Step F1
[0719] Step F1 in Method F is to prepare a compound of formula
(IIIa) and the compound is prepared by reacting a compound of
formula (XIV) with a compound of formula (XV).
[0720] The present step is carried out in a similar manner to that
described in Step B1 of Process B.
[0721] In the formula (XI) in Method C, the compound (XIa) in which
W is an aryloxy group, a hetero aryloxy group, an arylthio group or
a hetero arylthio group can be also prepared according to Method
G.
[0722] <<Method G>> 11
[0723] wherein R.sup.2, R.sup.3, R.sup.4, R.sup.7, R.sup.8, U,
W.sup.2, Y, Z and M have the same meanings as defined above.
[0724] Step G1
[0725] Step G1 in Method G is to prepare a compound of formula
(XIa) and the compound is prepared by reacting a compound of
formula (XVI) with a compound of formula (XV).
[0726] The present step is carried out in a similar manner to that
described in Step B1 of Process B.
[0727] In the formula (I) in Method A, a compound (Ia) in which
R.sup.4 is a hydrogen atom can be also prepared according to Method
H.
[0728] <<Method H>> 12
[0729] wherein R.sup.1, R.sup.2, R.sup.3, U.sup.1, W, W.sup.1, Y, Z
and M have the same meanings as defined above.
[0730] Step H1
[0731] Step H1 in Method H is to prepare a compound of formula
(XIX) and the compound is prepared by reacting a compound of
formula (XVII) with a compound of formula (XVIII).
[0732] The present reaction is carried out by reacting the
compounds in an inert solvent in the presence of a base.
[0733] The base employed here preferably includes alkali metal
hydrides such as sodium hydride, potassium hydride and lithium
hydride; alkali metal alkoxides such as sodium methoxide, sodium
ethoxide, potassium t-butoxide and lithium methoxide; alkyl
lithiums such as butyl lithium and methyl lithium; lithium amides
such as lithium diethylamide, lithium diisopropylamide and lithium
bis(trimethylsilyl)amide; or tertiary organic amines such as
1,5-diazabicyclo[4.3.0]non-5-ene and
1,8-diazabicyclo[5.4.0]undec-7-ene; more preferably alkali metal
hydrides, alkali metal alkoxides or lithium amides.
[0734] The inert solvent employed in the reaction is not
particularly limited so long as it has no adverse effect on the
reaction and includes, for example, hydrocarbons such as benzene
and toluene; ethers such as tetrahydrofuran and dioxane: alcohols
such as methanol, ethanol and t-butanol; amides such as
N,N-dimethylformamide, N,N-dimethylacetamide and
N-methylpyrrolidinone; ketones such as acetone and 2-butanone;
nitrites such as acetonitrile; sulfoxides such as dimethyl
sulfoxide; and mixtures thereof; preferably ethers, amides, ketones
or sulfoxides.
[0735] In the case where the present reaction is carried out in the
presence of a phase transfer catalyst such as
benzyltriethylammonium iodide and tetrabutylammonium iodide, the
present reaction is carried out in a two-layer solvent system of
water and a halogenated hydrocarbon such as methylene chloride and
chloroform using an alkali metal hydroxide such as sodium hydroxide
and potassium hydroxide as the base.
[0736] The reaction temperature is -10.degree. C. to 120.degree.
C., preferably 10.degree. C. to 100.degree. C.
[0737] While the reaction time varies depending on the reagent used
and the reaction temperature, it is usually 30 minutes to 48 hours,
preferably 1 hour to 16 hours.
[0738] Step H2
[0739] Step H2 is to prepare a phenylalkylcarboxylic acid
derivative of formula (Ia) and is carried out by removal of the
ester residues of the malonic acid diester derivative of formula
(XIX), and then by decarboxylation.
[0740] The removal of the ester residue in the present step is
accomplished by carrying out it in a similar manner to that
described in Step A2 of Method A.
[0741] The step of decarboxylation is accomplished by heating the
malonic acid derivative produced by removal of the ester residues
of the compound of formula (XIX) in the presence of a solvent.
[0742] The solvent employed in the present step is not particularly
limited so long as it has no adverse effect on the reaction and
includes, for example, hydrocarbons such as benzene, toluene,
xylene and heptane; halogenated hydrocarbons such as chloroform and
carbon tetrachloride; ethers such as tetrahydrofuran and dioxane;
alcohols such as ethanol, propanol, methoxyethanol and ethylene
glycol; amides such as N,N-dimethylformamide, N,N-dimethylacetamide
and hexamethylphosphoric triamide; and mixtures thereof; preferably
hydrocarbons or alcohols.
[0743] The reaction temperature is 60.degree. C. to 180.degree. C.,
preferably 80.degree. C. to 150.degree. C.
[0744] While the reaction time varies depending on the reagent, the
reaction temperature and the solvent, it is usually 30 minutes to 2
days, preferably 1 hour to 24 hours.
[0745] In the formula (I) of Method A, a compound (Ib) in which W
is an alkylamino group, a dialkylamino group or an aralkylamino
group can be also prepared according to Method I.
[0746] <<Method I>> 13
[0747] wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, Y, Z and M
have the same meanings as defined above. W.sup.3 represents a
straight or branched chain monoalkylamino group having from 1 to 4
carbon atoms, a straight or branched chain dialkylamino group in
which each alkyl group may be the same or different and each has
from 1 to 4 carbon atoms or an aralkylamino group having from 7 to
12 carbon atoms.
[0748] Step I1
[0749] Step I1 is to prepare a compound of formula (IIIc) and is
carried out by alkylation or aralkylation of a compound of formula
(IIIb).
[0750] The present reaction is carried out in a similar manner to
that described in Step B1 of Method B in the case where an alkyl
halide, aralkyl halide, alkyl sulfonate or aralkyl sulfonate is
used as an alkylation reagent.
[0751] In the case where the alkylation is reductively carried out
using a carbonyl compound, it is carried out in a similar manner to
that described in Step E1 of Method E.
[0752] Step I2
[0753] Step I2 is to prepare a compound of formula (Ib) and is
carried out by removal of the ester residue of the compound of
formula (IIIc).
[0754] The present step is carried out in a similar manner to that
described in Step A2 of Method A.
[0755] The desired compound obtained by each step described above
can be purified, if necessary, by conventional methods, for
example, column chromatography, recrystallization and
reprecipitation after the reaction. For example, the reaction
mixture is appropriately neutralized, a solvent is added to the
reaction mixture to extract it and the solvent is distilled off
from the extract. The residue thus obtained is purified by
subjecting it to column chromatography using silica gel to obtain
the purified product of the desired compound.
[0756] The amidocarboxylic acid derivatives of formula (I), the
pharmacologically acceptable salts thereof or the pharmacologically
acceptable esters thereof have some excellent effects of lowering
glucose, reducing lipid, ameliorating insulin resistance,
alleviating inflammatory disease, immunoregulation, inhibiting
aldose reductase, inhibiting 5-lipoxygenase, suppressing generation
of lipid peroxide, activating PPAR and alleviating osteoporosis and
are useful as preventive and/or therapeutic agents (particularly
therapeutic agents) for diseases caused by insulin resistance such
as diabetes mellitus, hyperlipemia, obesity, impaired glucose
torelance, insulin resistant non-impaired glucose torelance,
hypertension, fatty liver, diabetic complications (e.g.,
retinopathy, nephropathy, neurosis, cataracts, coronary artery
diseases, etc.), arteriosclerosis, gestational diabetes mellitus
and polycystic ovary syndrome, cell injury induced by
atherosclerosis and ischemic heart diseases (e.g., brain injury
caused by apoplexy); inflammatory diseases such as arthrosteitis,
pain, pyrexia, rheumatic arthritis, inflammatory enteritis, acne,
sunburn, psoriasis, eczema, allergic diseases, asthma, GI ulcers,
cancer, cachexia, autoimmune diseases and panceatitis;
osteoporosis; and cataracts, etc.
[0757] The amidocarboxylic acid derivatives of formula (I) of the
present invention, pharmacologically acceptable salts thereof or
esters thereof are administered in various forms. The
administration form is not particularly limited and is determined
depending on various kinds of pharmaceutical formulation forms,
age, sex and other conditions, the degree of disease of the
patient, etc. For example, the compound may be orally administered,
in the case of tablets, pills, powders, granules, syrups,
solutions, suspensions, emulsions, granules and capsules.
Meanwhile, in the case of injections, it is intravenously
administered singly or in a mixture with a usual adjuvant solution
such as glucose, an amino acid, etc. Furthermore, if necessary, it
may be singly administered intramuscularly, intracutaneously,
subcutaneously or intraperitoneally. In the case of suppositories,
it is intrarectally administered. Oral administration is
preferable. The various kinds of these pharmaceutical formulations
can be prepared using known adjuvants usually used in the known
pharmaceutical formulation field such as excipients, binders,
disintegrators, lubricants, solubilizers, corrigents, and coating
agents for a principal agent according to a conventional
method.
[0758] When the present component is molded into the form of
tablets, carriers known to one of ordinary skill in the art can be
widely used, and includes excipients such as lactose, sucrose,
sodium chloride, glucose, urea, starch, calcium carbonate, kaolin,
crystalline cellulose and silicic acid; binders such as water,
ethanol, propanol, single syrup, glucose solution, starch solution,
gelatin solution, carboxymethyl cellulose, shellac, methyl
cellulose, potassium phosphate, and polyvinylpyrrolidone;
disintegrators such as dry starch, sodium alginate, agar powder,
laminaran powder, sodium hydrogencarbonate, calcium carbonate,
polyoxyethylenesorbitan aliphatic acid ester, sodium lauryl
sulfate, stearic acid monoglyceride, starch and lactose;
disintegration inhibiting agents such as sucrose, stearic acid,
cacao butter and hydrogenated oil; absorption accelerating agents
such as a quaternary ammonium base and sodium lauryl sulfate;
humectants such as glycerin and starch; adsorbents such as starch,
lactose, kaolin, bentonite and colloidal silicic acid; and
lubricants such as purified talc, a stearate, boric acid powder and
polyethylene glycol. Further, the tablets can be made, if
necessary, as tablets to which is applied a coating film, for
example, a sugar coating tablet, a gelatin coating tablet, an
enteric coated tablet, a film coating tablet, a double layer tablet
or a multilayer tablet.
[0759] When the present compound is molded into the form of pills,
carriers known to one of ordinary skill in the art can be widely
used, and include, for example, excipients such as glucose,
lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin
and talc; binders such as gum Arabic powder, tragacanth powder,
gelatin and ethanol; and disintegrants such as laminaran agar. When
the present compound is molded into the form of suppositories,
carriers known to one of ordinary skill in the art can be widely
used, and include, for example, polyethylene glycol, cacao butter,
higher alcohols, esters of higher alcohol, gelatin and
semi-synthetic glyceride.
[0760] In the case where the present compound is formulated as an
injection, it is preferable that the solvents and suspending agents
are sterilized and are isotonic to blood. When the present compound
is formulated into such solutions, emulsions and suspensions, all
diluents conventionally used in this field can be used, and
include, for example, water, ethyl alcohol, propylene glycol,
ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol and
polyoxyethylenesorbitan aliphatic acid ester. Incidentally, in this
case, a sufficient amount of NaCl, glucose or glycerin in order to
prepare an isotonic solution may be contained in the pharmaceutical
formulations. Further, conventional solubility improving agents,
buffers and soothing agents may also be added thereto.
[0761] Further, colorants, preservatives, flavors, sweeteners and
other pharmaceuticals may be contained therein, if necessary.
[0762] The amount of the active ingredient contained in the
above-mentioned pharmaceutical formulations is not particulaly
limited and is appropriately selected from a wide range, and it is
preferable that the content is usually from 1 to 70% by weight in
all compositions, more preferably from 1 to 30% by weight.
[0763] While the does will vary depending on the animal's symptoms,
age and body weight, and on the administration methods and form of
the pharmaceutical formulations, it is usually administered in an
amount of 0.000002 mg/kg (preferably 0.00002 mg/kg, more preferably
0.0002 mg/kg) as a lower limit and 40 mg/kg (preferably 4 mg/kg,
more preferably 0.4 mg/kg) as an upper limit. For adult humans, it
is usually administered in an amount of 0.0001 mg (preferably 0.001
mg, more preferably 0.01 mg) as a lower limit and 2000 mg
(preferably 200 mg, more preferably 20 mg) as an upper limit from
once to several times per day to an adult.
[0764] The following examples, reference examples, test examples
and formulation examples are intended to further illustrate the
present invention and are intended in no way to limit the scope of
the invention.
[0765] All .sup.1H-NMR spectra were determined in the solvents
indicated and chemical shifts are reported in .delta. units
downfield from the internal standard tetramethylsilane (TMS) and
interproton coupling constants are reported in Hertz (Hz).
EXAMPLE 1
Ethyl
2-ethoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propiona-
te (ethyl ester of exemplification No. 1-35 compound)
[0766] Hydrazine-hydrate (80%, 0.125 ml) was added to a solution of
ethyl 2-ethoxy-3-[4-(2-phthaloyliminoethoxy)phenyl]propionate (760
mg), which is the product of reference example 1, in methanol (5
ml) and the mixture was allowed to stand at room temperature for
1.5 hours. At the end of this time the reaction mixture was
concentrated. The residue was partitioned between ethyl acetate and
water and the layers were separated. The ethyl acetate layer was
dried over anhydrous sodium sulfate and concentrated by evaporation
in vacuum to afford an amino derivative.
[0767] Separately, carbonyldiimidazole (400 mg) was added to a
suspension of 4-pyridine-2-ylbenzoic acid (400 mg) in anhydrous
dichloromethane (10 ml) and the mixture was stirred at room
temperature for 1.5 hours to give a clear solution. To this clear
solution, a solution of the amino derivative produced as described
above in dichloromethane (5 ml) was added and the mixture was
stirred at room temperature for 30 minutes. To this reaction
mixture 4-pyridine-2-ylbenzoic acid (200 mg) and
carbonyldiimidazole (170 mg) were added. After the mixture was
allowed to stand overnight, the reaction mixture was concentrated
by evaporation in vacuum. The residue was partitioned between ethyl
acetate and water and the layers were separated. The organic layer
was dried over anhydrous magnesium sulfate and evaporated under
reduced pressure. The residue was purified via chromatography on a
silica gel column using dichloromethane/methanol=20/1 as the eluant
to afford the title compound (135 mg) as a gum.
[0768] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.08-1.29
(6H, m), 2.95 (2H, d, J=6.5 Hz), 3.35 (1H, quintuplet, J=7.0 Hz),
3.60 (1H, quintuplet, J=7.0 Hz), 3.83-4.30 (7H, m), 6.72 (1H, t,
J=4.5 Hz), 6.86 (1H, t, J=8.5 Hz), 7.17 (2H, d, J=8.5 Hz),
7.25-7.40 (1H, m), 7.72-8.01 (4H, m), 8.07 (2H, d, J=8.5 Hz),
8.70-8.80 (1H,m).
EXAMPLE 2
Sodium
2-ethoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propion-
ate (exemplification No. 1-35 compound)
[0769] To a solution of ethyl
2-ethoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (135 mg), which is the product of
Example 1, in methanol (2 ml) an aqueous solution of sodium
hydroxide (1N, 0.55 ml) was added. The mixture was stirred at room
temperature for 2 hours. At the end of this time the methanol was
evaporated under reduced pressure and an aqueous solution of
hydrogen chloride (1N, 0.55 ml) and ethyl acetate were added to the
residue. The ethyl acetate layer was separated and dried over
anhydrous magnesium sulfate and then concentrated under reduced
pressure to afford the desired compound (121 mg) as a gum.
[0770] An aqueous 1N sodium hydroxide solution (0.28 ml) was added
to a solution of the desired compound in methanol (3 ml) and the
mixture was concentrated in vacuum to give the title compound (128
mg) as an amorphous solid.
[0771] .sup.1H-NMR (270 MHz, deuterated dimethylsulfoxide): .delta.
ppm 1.00 (3H, t, J=7.0 Hz), 2.66 (2H, dd, J=9.0, 14.0 Hz), 2.88
(2H, dd, J=3.5, 14.0 Hz), 3.42-3.70 (5H, m), 4.05-4.13 (1H, m),
6.83 (2H, d, J=8.5 Hz), 7.14 (2H, d, J=8.5 Hz), 7.32-41 (1H, m),
7.85-8.09 (4H, m), 8.17 (2H, d, J=8.5 Hz), 8.69 (1H, d, J=4.0 Hz),
8.80 (1H, t, J=5.5 Hz).
EXAMPLE 3
Ethyl
2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 9-35 compound)
[0772] In a similar manner to that described in Example 1, a
reaction was carried out using ethyl
2-(3-phenylpropyl)-3-[4-(2-phthaloyliminoethoxy)p- henyl]propionate
(1.50 g), which is the product of Reference example 2,
4-pyridine-2-ylbenzoic acid (285 mg) and carbonyldiimidazole (255
mg) and the reaction mixture was treated, to give the title
compound (984 mg) as a gum.
[0773] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.14 (3H, t,
J=7.0 Hz), 1.47-1.73 (4H, m), 2.50-2.70 (4H, m), 2.80-2.92 (1H, m),
3.89 (2H, dt, J=5.0, 5.0 Hz), 4.04 (2H, q, J=7.0 Hz), 4.15 (2H, t,
J=5.0 Hz), 6.67 (1H, t, J=5.0 Hz), 6.84 (2H, d, J=8.5 Hz), 7.07
(2H, d, J=8.5 Hz), 7.10-7.20 (3H, m), 7.20-7.31 (3H, m), 7.73-7.79
(2H, m), 7.90 (2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.71 (1H,
d, J=5.0 Hz).
EXAMPLE 4
2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionic acid (exemplification No. 9-35 compound)
[0774] In a similar manner to that described in Example 2, ethyl
2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate (767 mg), which is the product of Example 3, was reacted
with an aqueous sodium hydroxide solution (1N, 2.86 ml) and the
reaction mixture was treated. The residue was crystallized from a
mixture of diisopropyl ether and ethyl acetate to give the title
compound (361 mg) as colorless crystals.
[0775] mp 114-116.degree. C.
[0776] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.50-1.79
(4H, m), 2.57-2.75 (4H, m), 2.80-2.94 (1H, m), 3.85 (2H, q, J=5.5
Hz), 4.13-4.20 (2H, m), 6.69 (1H, t, J=5.5 Hz), 6.83 (2H, d, J=8.5
Hz), 7.07 (2H, d, J=8.5 Hz), 7.10-7.20 (3H, m), 7.22-7.32 (3H, m),
7.70-7.84 (4H, m), 7.97 (2H, d, J=8.5 Hz), 8.67-8.71 (1H, m).
EXAMPLE 5
Ethyl
2-(2-phenoxyethyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 138-2
compound)
[0777] Carbonyldiimidazol (272 mg) was added to a suspension of
4-pyridine-2-ylbenzoic acid (279 mg) in dichloromethane (8 ml). The
mixture was stirred at ambient temperature for 30 minutes to afford
a clear solution. To this solution, a solution of ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(2-phenoxyethyl)propionate (476 mg),
which is the product of Reference example 3, in methylene chloride
(5 ml) was added and the mixture was stirred at ambient temperature
for 30 minutes and allowed to stand overnight. At the end of this
time the reaction mixture was concentrated and the residue was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and dried over anhydrous magnesium sulfate and
then concentrated under reduced pressure. The residue was purified
via chromatography on silica gel column using dichloromethane/ethyl
acetate=1/1 as the eluant to give the title compound (374 mg) as a
gum.
[0778] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.14 (3H, t,
J=7.0 Hz), 1.90-2.21 (2H, m), 2.76-3.10 (3H, m), 3.87-4.19 (8H, m),
6.65-6.69 (1H, m), 6.82-6.89 (4H, m), 6.93 (1H, t, J=7.5 Hz), 7.12
(2H, d, J=8.5 Hz), 7.23-7.32 (3H, m), 7.76-7.83 (2H, m), 7.90 (2H,
d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz), 8.72-8.75 (1H, m).
EXAMPLE 6
2-(2-Phenoxyethyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionic acid (exemplification No. 138-2 compound)
[0779] An aqueous solution of potassium hydroxide (85%, 0.13 g) was
added to a solution of ethyl
2-(2-phenoxyethyl)-3-[4-[2-(4-pyridine-2-ylbenzoyl-
amino)ethoxy]phenyl]propionate (350 mg) in ethanol (8 ml). The
mixture was stirred at 80.degree. C. for 3 hours. At the end of
this time the ethanol was evaporated under reduced pressure. An
aqueous solution of hydrogen chloride (1N, 2.0 ml) and ethyl
acetate was added to the residue. The ethyl acetate layer was
separated and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure to give the title compound (260
mg) as a mass of foam.
[0780] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.93-2.22
(2H, m), 2.78-3.02 (3H, m), 3.86 (2H, dt, J=5.0, 5.5 Hz), 4.00-4.08
(2H, m), 4.16-4.21 (2H, m), 6.65-6.69 (1H, m), 6.82-6.97 (5H, m),
7.12 (2H, d, J=8.5 Hz), 7.22-7.34 (3H, m), 7.72-7.85 (4H, m), 7.97
(2H, d, J=8.5 Hz), 8.68-8.71 (1H, m).
[0781] An aqueous sodium hydroxide solution (1N, 0.51 ml) was added
to a solution of the mass of foam in ethanol (3 ml). The mixture
was concentrated to give a solid which was washed with diethyl
ether to afford the title compound (203 mg) as an amorphous
solid.
EXAMPLE 7
Ethyl
2-phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propion-
ate (ethyl ester of exemplification No. 6-35 compound)
[0782] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (660 mg), which is
the product of Reference example 4, 4-pyridine-2ylbenzoic acid (428
mg) and carbonyldiimidazole (418 mg) and the reaction mixture was
treated to give the title compound (367 mg) as a white powder.
[0783] mp 118.5-120.degree. C.
[0784] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.17-3.22 (2H, m), 3.89 (2H, dt, J=5.0, 5.5 Hz),
4.13-4.22 (4H, m), 4.74 (1H, dd, J=5.5, 7.0 Hz), 6.63-6.69 (1H, m),
6.84 (2H, d, J=9.0 Hz), 6.87 (2H, d, J=9.0 Hz), 6.94 (1H, t, J=7.5
Hz), 7.20-7.30 (5H, m), 7.75-7.80 (2H, m), 7.90 (2H, d, J=8.5 Hz),
8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 8
2-Phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 6-35 compound)
[0785] In a similar manner to that described in Example 6, ethyl
2-phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(327 mg), which is the product of Example 7, was reacted with
aqueous potassium hydroxide solution (85%, 200 mg) and the reaction
mixture was treated to give the title compound (280 mg) as
colorless crystals.
[0786] mp 149-151.degree. C.
[0787] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.21 (2H, d,
J=7.0 Hz), 3.87 (2H, dt, J=5.0, 5.5 Hz), 4.14-4.18 (2H, m), 4.73
(1H, t, J=7.0 Hz), 6.84-6.94 (6H, m), 7.19-7.31 (5H, m), 7.75-7.80
(2H, m), 7.88 (2H, d, J=8.5 Hz), 8.05 (2H, d, J=8.5 Hz), 8.71 (1H,
d, J=4.5 Hz).
EXAMPLE 9
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]p-
henyl]propionate (ethyl ester of exemplification No. 7-35
compound)
[0788] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy- )propionate
(13.52 g), which is the product of Reference example 5,
4-pyridine-2-ylbenzoic acid (7.97 g) and carbonyldiimidazole (6.49
g) and the reaction mixture was treated and then the residue was
crystallized from diisopropyl ether to give the title compound
(8.38 g) as colorless crystals.
[0789] mp 77-79.degree. C.
[0790] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.14-1.25
(9H, m), 2.72-2.90 (1H, m), 3.12-3.19 (2H, m), 3.89 (2H, dt, J=5.0,
5.5 Hz), 4.11-4.22 (4H, m), 4.69 (1H, dd, J=5.5, 7.5 Hz), 6.65 (1H,
brt), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.08 (2H, d,
J=8.5 Hz), 7.20-7.31 (3H, m), 7.76-7.81 (2H, m), 7.88 (2H, d, J=8.5
Hz), 8.07 (2H, d, J=8.5 Hz), 8.69-8.75 (1H, m).
EXAMPLE 10
2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-
propionic acid (exemplification No. 7-35 compound)
[0791] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl-
]propionate (8.38 g), which is the product of Example 9, was
reacted with aqueous sodium hydroxide solution (IN, 30.32 ml) and
the reaction mixture was treated to give the title compound (7.95
g) as a white powder.
[0792] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.16 (6H, d,
J=7.0 Hz), 2.70-2.88 (1H, m), 3.19 (2H, d, J=6.0 Hz), 3.80-3.89
(2H, m), 4.11-4.18 (2H, m), 4.77 (1H, t, J=6.0 Hz), 6.77-6.88 (5H,
m), 7.07 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 7.25-7.35 (1H,
m), 7.70 (1H, d, J=8.5 Hz), 7.75-7.86 (3H, m), 7.89 (2H, d, J=8.5
Hz), 8.70-8.77 (1H, m).
EXAMPLE 11
Ethyl
2-butyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionat-
e (ethyl ester of exemplification No. 4-35 compound)
[0793] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (1.49 g), which is
the product of Reference example 6, 4-pyridine-2-ylbenzoic acid
(996 mg) and carbonyldiimidazole (810 mg) and the reaction mixture
was treated to give the title compound (1.04 g) as a white
powder.
[0794] mp 112-115.degree. C.
[0795] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=6.5 Hz), 1.16 (3H, t, J=7.0 Hz), 1.20-1.37 (4H, m), 1.39-1.68
(2H, m), 2.35-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.89 (2H, t, J=5.0 Hz), 4.06 (2H, q,
J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.66 (1H, brs), 6.84 (2H, d,
J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.21-7.31 (1H, m), 7.77-7.79
(2H, m), 7.89 (2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.72 (1H,
d, J=4.5 Hz).
EXAMPLE 12
2-butyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-35 compound)
[0796] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(0.92 g), which is the product of Example 11, was reacted with
aqueous sodium hydroxide solution (1N, 3.80 ml) and the reaction
mixture was treated to give the title compound (1.06 g) as a white
powder.
[0797] mp 137-139.degree. C.
[0798] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.21-1.42 (4H, m), 1.45-1.70 (2H, m), 2.57-2.80 (1H, m),
2.70 (1H, dd, J=5.0, 13.5 Hz), 2.87 (1H, dd, J=9.0, 13.5 Hz), 3.86
(2H, t, J=5.0 Hz), 4.17 (2H, t, J=5.0 Hz), 6.77 (1H, brs), 6.83
(2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.23-7.38 (1H, m),
7.72-7.75 (2H, m), 7.79 (2H, d, J=8.5 Hz), 7.98 (2H, d, J=8.5 Hz),
8.70 (1H, d, J=4.5 Hz).
EXAMPLE 13
Ethyl
2-methyl-2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-yl-benzoylamino)et-
hoxy]phenyl]propionate (ethyl ester of exemplification No. 37-3
compound)
[0799] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-(3-phenylp- ropyl)propionate
(796 mg), which is the product of Reference example 7,
4-pyridine-2-ylbenzoic acid (438 mg) and carbonyldiimidazole (428
mg) and the reaction mixture was treated to give the title compound
(285 mg) as a colorless oil.
[0800] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.05 (3H, s),
1.24 (3H, t, J=7.0 Hz), 1.38-1.80 (4H, m), 2.56-2.65 (3H, m), 2.94
(1H, d, J=13.0 Hz), 3.89 (2H, dt, J=5.0, 5.5 Hz), 4.07-4.18 (4H,
m), 6.65 (1H, brs), 6.80 (2H, d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz),
7.14-7.30 (6H, m), 7.75-7.79 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.08
(2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 14
Sodium
2-methyl-2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-yl-benzoylamino)e-
thoxy]phenyl]propionate (exemplification No. 37-3 compound)
[0801] In a similar manner to that described in Example 6, ethyl
2-methyl-2-(3-phenylpropyl)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]p-
henyl]propionate (0.131 mg), which is the product of Example 13,
was reacted with aqueous potassium hydroxide solution (85%, 0.24 g)
and the reaction mixture was treated. The residue was subjected to
chromatography on a silica gel column using
dichloromethane/methanol=20/1 as the eluant to afford the desired
compound. An aqueous solution of sodium hydroxide (1N, 0.37 ml) was
added to the desired compound and the mixture was concentrated to
afford a solid. The solid was washed with diisopropyl ether to give
the title compound (177 mg) as a white powder.
[0802] mp 108-111.degree. C.
[0803] .sup.1H-NMR (270 MHz, deuterated dimethylsulfoxide): .delta.
ppm 1.01 (3H, s), 1.15-1.85 (4H, m), 2.55-2.78 (3H, m), 3.03 (1H,
d, J=13.0 Hz), 3.71-3.93 (2H, m), 4.13-4.38 (2H, m), 6.97 (2H, d,
J=8.5 Hz), 7.21-7.69 (8H, m), 8.08-8.45 (6H, m), 8.86-8.98 (1H, m),
9.09-9.15 (1H, m).
EXAMPLE 15
Ethyl
2-methyl-2-phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 33-3 compound)
[0804] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-phenoxypro- pionate (760
mg), which is the product of Reference example 8,
4-pyridine-2-ylbenzoic acid (460 mg) and carbonyldiimidazole (440
mg) and the reaction mixture was treated to give the title compound
(930 mg) as a syrup.
[0805] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 1.40 (3H, s), 3.11 (1H, d, J=14.0 Hz), 3.29 (1H, d,
J=14.0 Hz), 3.89 (2H, dt, J=5.0, 5.5 Hz), 4.10-4.25 (2H, m), 4.18
(2H, q, J=7.0 Hz), 6.71 (1H, brs), 6.75-6.86 (4H, m), 6.97 (1H, t,
J=7.0 Hz), 7.13-7.33 (5H, m), 7.74-7.84 (2H, m), 7.89 (2H, d, J=8.5
Hz), 8.07 (2H, d, J=8.5 Hz), 8.71 (1H, d, J=5.0 Hz).
EXAMPLE 16
2-Methyl-2-phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionic acid (exemplification No. 33-3 compound)
[0806] In a similar manner to that described in Example 2, ethyl
2-methyl-2-phenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate (930 mg), which is the product of Example 15, was reacted
with aqueous sodium hydroxide solution (1N, 3.60 ml) at 70.degree.
C. and the reaction mixture was treated to give the title compound
(545 mg) as a white powder.
[0807] mp 76-79.degree. C.
[0808] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.44 (3H, s),
3.15 (1H, d, J=14.0 Hz), 3.28 (1H. d, J=14.0 Hz), 3.87 (2H, t J=5.0
Hz), 4.16 (2H, t, J=5.0 Hz), 6.75 (1H, brs), 6.84 (2H, d, J=8.5
Hz), 6.92 (2H, d, J=8.5 Hz), 6.97 (1H, t, J=7.0 Hz), 7.15-7.34 (5H,
m), 7.70-7.88 (4H, m), 7.97 (2H, d, J=8.5 Hz), 8.73 (1H, d, J=4.0
Hz).
EXAMPLE 17
Ethyl
2-(4-isopropylphenoxy)-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino-
)ethoxy]phenyl]propionate (ethyl ester of exemplification No. 34-3
compound)
[0809] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy-
)-2-methylpropionate (510 mg), which is the product of Reference
example 9, 4-pyridine-2-ylbenzoic acid (279 mg) and
carbonyldiimidazole (272 mg) and the reaction mixture was treated
to give the title compound (487 mg) as a colorless oil.
[0810] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.37 (3H, s), 2.83 (1H, septet,
J=7.0 Hz), 3.10 (1H, d, J=13.5 Hz ), 3.26 (1H, d, J=13.5 Hz), 3.90
(2H, dt, J=5.0, 5.0 Hz), 4.17 (2H, t, J=5.0 Hz), 4.21 (2H, q, J=7.0
Hz), 6.69 (1H, brt, J=5.0 Hz), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d,
J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz), 7.19 (2H, d, J=8.5 Hz),
7.25-7.32 (1H, m), 7.76-7.79 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07
(2H, d, J=8.5 Hz), 8.71-8.73 (1H, m).
EXAMPLE 18
2-(4-Isopropylphenoxy)-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethox-
y]phenyl]propionic acid (exemplification No. 34-3 compound)
[0811] In a similar manner to that described in Example 6, ethyl
2-(4-isopropylphenoxy)-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)etho-
xy]phenyl]propionate (486 mg), which is the product of Example 17,
was reacted with aqueous potassium hydroxide solution (85%, 0.17 g)
and the reaction mixture was treated. The residue was washed with
diisopropyl ether to give the title compound (335 mg) as a white
powder.
[0812] mp 141-143.degree. C.
[0813] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.43 (3H, s), 2.84 (1H, septet, J=7.0 Hz), 3.15 (1H, d,
J=14.0 Hz), 3.25 (1H, d, J=14.0 Hz), 3.83-3.93 (2H, m), 4.17 (2H,
t, J=5.0 Hz), 6.70 (1H, brt, J=6.0 Hz), 6.85 (2H, d, J=8.5 Hz),
6.86 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5
Hz), 7.27-7.33 (1H, m), 7.72-7.80 (2H, m), 7.83 (2H, d, J=8.5 Hz),
8.00 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 19
Ethyl
2-butyl-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-
propionate (ethyl ester of exemplification No. 30-3 compound)
[0814] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butyl-2-methylpropi- onate (2.42 g),
which is the product of Reference example 10,
4-pyridine-2-ylbenzoic acid (1.72 g) and carbonyldiimidazole (1.69
g) and the reaction mixture was treated to give the title compound
(970 mg) as a white powder.
[0815] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.12-1.46 (8H, m), 1.60-1.77 (1H, m), 2.63
(1H, d, J=13.5 Hz), 2.97 (1H, d, J=13.5 Hz), 3.86-3.93 (2H, m),
4.07-4.18 (4H, m), 6.68 (1H, brt, J=5.0 Hz), 6.82 (2H, d, J=8.5
Hz), 7.03 (2H, d, J=8.5 Hz), 7.24-7.31 (1H, m), 7.76-7.80 (2H, m),
7.89 (2H, d. J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.71-8.73 (1H,
m).
EXAMPLE 20
2-Butyl-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propio-
nic acid (exemplification No. 30-3 compound)
[0816] In a similar manner to that described in Example 6, ethyl
2-butyl-2-methyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propi-
onate (350 mg), which is the product of Example 19, was reacted
with aqueous sodium hydroxide solution (1N, 2.00 ml) and aqueous
potassium hydroxide solution (85%, 0.1 g) and the reaction mixture
was treated. The residue was subjected to chromatography on a
silica gel column using dichlorometane/methanol=19/1 as the eluant
to afford a solid which was washed with a mixture of diisopropyl
ether and hexane to give the title compound (133 mg) as a white
powder.
[0817] mp 105.5-107.5.degree. C.
[0818] .sup.1H-NMR (270 MHz, CDCl1.sub.3): .delta. ppm 0.91 (3H, t,
J=7.0 Hz), 1.09 (3H, s), 1.20-1.48 (5H, m), 1.66-1.78 (1H, m), 2.64
(1H, d, J=13.5 Hz), 3.00 (1H, d, J=13.5 Hz), 3.83-3.93 (2H, m),
4.09-4.18 (2H, m), 6.79-6.83 (1H, m), 6.81 (2H, d, J=8.5 Hz), 7.07
(2H, d, J=8.5 Hz), 7.25-7.32 (1H, m), 7.73-7.83 (2H, m), 7.87 (2H,
d, J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz), 8.71 (1H, d, J=5.0 Hz).
EXAMPLE 21
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-butylpropionate
(ethyl ester of exemplification No. 4-15 compound)
[0819] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (666 mg), which is
the product of Reference example 6, biphenyl-4-carboxylic acid (450
mg) and carbonyldiimidazole (442 mg) and the reaction mixture was
treated to give the title compound (705 mg) as a yellow powder.
[0820] mp 89-90.degree. C.
[0821] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.32 (4H, m), 1.40-1.69
(2H, m), 2.53-2.63 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.89 (2H, q, J=5.0 Hz), 4.07 (2H, q,
J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.63 (1H, t, J=5.0 Hz), 6.85
(2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.37-7.50 (3H, m),
7.60-7.68 (4H, m), 7.86 (2H, d, J=8.5 Hz).
EXAMPLE 22
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-butylpropionic
acid (exemplification No. 4-15 compound)
[0822] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-butylpropionate
(450 mg), which is the product of Example 21, was reacted with
aqueous sodium hydroxide solution (1N, 3.00 ml) and the reaction
mixture was treated to give the title compound (388 mg) as a white
powder.
[0823] mp 130-131.degree. C.
[0824] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.88 (3H, t,
J=7.0 Hz), 1.25-1.43 (4H, m), 1.46-1.73 (2H, m), 2.58-2.66 (1H, m),
2.72 (1H, dd, J=6.5, 13.5 Hz), 2.89 (1H, dd, J=8.5, 13.5 Hz), 3.87
(2H, q, J=5.0 Hz), 4.13 (2H, t, J=5.0 Hz), 6.71 (1H, t, J=5.0 Hz),
6.84 (2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.35-7.49 (3H, m),
7.58-7.70 (4H, m), 7.85 (2H, d, J=8.5 Hz).
EXAMPLE 23
Ethyl
2-butyl-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-179 compound)
[0825] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (540 mg), which is
the product of Reference example 6, 4'-methoxybiphenyl-4-carboxylic
acid (420 mg) and carbonyldiimidazole (370 mg) and the reaction
mixture was treated to give the title compound (486 mg) as a white
powder.
[0826] mp 121-123.degree. C.
[0827] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.38 (4H, m), 1.42-1.70
(2H, m), 2.51-2.72 (2H, m), 2.80-2.92 (1H, m), 3.86 (3H, s),
3.87-3.92 (2H, m), 4.07 (2H, q, J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz),
6.62 (1H, t, J=5.5 Hz), 6.84 (2H, d, J=8.5 Hz), 7.00 (2H, d, J=8.5
Hz), 7.09 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz), 7.62 (2H, d,
J=8.5 Hz), 7.83 (2H, d, J=8.5 Hz).
EXAMPLE 24
2-Butyl-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-179 compound)
[0828] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (400 mg), which is the product of Example 23, was reacted with
aqueous sodium hydroxide solution (1N, 4.00 ml) and the reaction
mixture was treated to give the title compound (350 mg) as a pale
orange powder.
[0829] mp 166.5-168.degree. C.
[0830] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.23-1.40 (4H, m), 1.43-1.71 (2H, m), 2.57-2.78 (2H, m),
2.85-2.97 (1H, m), 3.86 (3H, s), 3.82-3.90 (2H, m), 4.13 (2H, t,
J=5.0 Hz), 6.69 (1H, t, J=5.5 Hz), 6.83 (2H, d, J=8.5 Hz), 6.98
(2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz),
7.60 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz).
EXAMPLE 25
Ethyl
2-butyl-3-[4-[2-(4'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-206 compound)
[0831] 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
(359 mg) and 1-hydroxybenzotriazole monohydrate (287 mg) were added
to a suspension of 4'-hydroxybiphenyl-4-carboxylic acid (383 mg) in
dichloromethane (10 ml) at ambient temperature. The mixture was
stirred for 4 hours at ambient temperature. A solution of ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (500 mg), which is
the product of Reference example 6, in dichloromethane (10 ml) was
then added to the reaction mixture. The mixture was stirred at
ambient temperature for 2 hours and then allowed to stand
overnight. At the end of this time the reaction mixture was
concentrated by evaporation. The residue was partioned between
ethyl acetate and water. The layers were separated. The ethyl
acetate layer was washed with aqueous hydrogen chloride solution
(0.5N), saturated aqueous sodium bicarbonate solution and saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and then concentrated under reduced pressure. The residue
was purified via chromatography on a silica gel column using
dichloromethane/ethyl acetate=5/1 as the eluant to give the title
compound (270 mg) as a colorless oil.
[0832] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.21-1.37 (4H, m), 1.40-1.70
(2H, m), 2.55-2.64 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.88 (2H, q, J=5.0 Hz), 4.05 (2H, q,
J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz), 6.36 (1H, brs), 6.65 (1H, t,
J=5.0 Hz), 6.83 (2H, d, J=8.5 Hz), 6.93 (2H, d, J=8.5 Hz), 7.08
(2H, d, J=8.5 Hz), 7.49 (2H, d, J=8.5 Hz), 7.60 (2H, d, J=8.5 Hz),
7.82 (2H, d, J=8.5 Hz).
EXAMPLE 26
2-Butyl-3-[4-[2-(4'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-206 compound)
[0833] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (260 mg), which is the product of Example 25, was reacted with
aqueous sodium hydroxide solution (1N, 2.20 ml) and the reaction
mixture was treated to give the title compound (230 mg) as a white
powder.
[0834] mp 182-184.degree. C.
[0835] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 0.79 (3H, t, J=6.5 Hz), 1.15-1.30 (4H, m), 1.34-1.53
(2H, m), 2.40-2.50 (1H, m), 2.57 (1H, dd, J=6.0, 13.5 Hz), 2.71
(1H, dd, J=8.5, 13.5 Hz), 3.59 (2H, q, J=5.5 Hz), 4.05 (2H, t,
J=5.5 Hz), 6.83 (4H, d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz), 7.53
(2H, d, J=8.5 Hz), 7.63 (2H, d, J=8.5 Hz), 7.87 (2H, d, J=8.5 Hz),
8.63 (1H, t, J=5.5 Hz), 9.61 (1H, s).
EXAMPLE 27
2-Butyl-3-[4-[2-(4'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-207 compound)
[0836] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4'-dimethoxymethylbiphenyl-4-carbonylamino)ethoxy]phenyl-
]propionate (1.88 g), which is the product of Reference example 11,
was reacted with aqueous sodium hydroxide solution (1N, 6.80 ml)
and the reaction mixture was treated to give
2-butyl-3-[4-[2-(4'-dimethoxymethylb-
iphenyl-4-carbonylamino)ethoxy]phenyl]propionic acid (1.78 g) as a
pale brown solid.
[0837] To a solution of this compound (521 mg) in acetone (15 ml),
water (0.17 ml) was added and then amberlyst 15 (100 mg) was added
at ambient temperature. The mixture was allowed to stand for 40
minute. The amberlyst 15 was removed by filtration and the filtrate
was concentrated. The residue was purified via chromatography on
silica gel column using dichloromethane/methanol=20/1 as the eluant
to give the title compound (336 mg) as a white solid.
[0838] mp 122-124.degree. C.
[0839] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.88 (3H, t,
J=7.0 Hz), 1.20-1.37 (4H, m), 1.40-1.59 (1H, m), 1.61-1.71 (1H, m),
2.58-2.69 (1H, m), 2.72 (1H, dd, J=6.5, 13.5 Hz), 2.90 (1H, dd,
J=8.5, 13.5 Hz), 3.89 (2H, q, J=5.0 Hz), 4.15 (2H, t, J=5.0 Hz),
6.71 (1H, brt), 6.84 (2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz),
7.69 (2H, d, J=8.5 Hz), 7.76 (2H, d, J=8.5 Hz), 7.89 (2H, d, J=8.5
Hz), 7.97 (2H, d, J=8.5 Hz), 10.08 (1H, s).
EXAMPLE 28
2-Butyl-3-[4-[2-(4'-hydroxymethylbiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionic acid (exemplification No. 4-211 compound)
[0840] Sodium borohydride (95%, 34 mg) was added to a solution of
2-butyl-3-[4-[2-(4'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (366 mg) in ethanol (10 ml) at ambient temperature. The
mixture was stirred for 1.5 hours. At the end of this time 50%
acetic acid was added to the reaction mixture. The mixture was
concentrated under reduced pressure. The residue was partitioned
between ethyl acetate and water. The ethyl acetate layer was
separated and washed with saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate and then
concentrated under reduced pressure. Diisopropyl ether was added to
the residue to give the title compound (331 mg) as colorless
crystals.
[0841] mp 111-113.degree. C.
[0842] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 0.88
(3H, t, J=7.0 Hz), 1.22-1.39 (4H, m), 1.40-1.65 (2H, m), 2.52-2.61
(1 H, m), 2.67 (1H, dd, J=6.5, 13.5 Hz), 2.86 (1H, dd, J=8.0, 13.5
Hz), 3.80 (2H, t, J=5.5 Hz), 4.16 (2H, t, J=5.5 Hz), 4.68 (2H, s),
6.87 (2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.46 (2H, d, J=8.5
Hz), 7.63 (2H, d, J=8.5 Hz), 7.70 (2H, d, J=8.5 Hz), 7.90 (2H, d,
J=8.5 Hz).
EXAMPLE 29
2-Butyl-3-[4-[2-(4'-dimethylaminomethylbiphenyl-4-carbonyl
amino)ethoxy]phenyl]propionic acid (exemplification No. 4-208
compound)
[0843] To triethylamine (0.56 ml), dimethylamine hydrochloride (167
mg) and titanium tetraisopropoxide (0.59 ml) was added a suspension
of
2-butyl-3-[4-[2-(4'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (474 mg) in ethanol (20 ml) at ambient temperature to afford
a clear solution. Sodium borohydride (60 mg) was added to the
solution and the mixture was stirred under nitrogen atmosphere for
18 hours. At the end of this time 50% acetic acid was added to the
reaction mixture. This mixture was concentrated under reduced
pressure. The residue was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and washed with
saturated aqueous sodium chloride solution and dried over anhydrous
magnesium sulfate and then concentrated under reduced pressure.
Diisopropyl ether was added to the residue to give the title
compound (135 mg) as colorless crystals.
[0844] mp 125-127.degree. C.
[0845] .sup.1H-NMR (400 MHz, deuterated methanol): .delta. ppm 0.87
(3H, t, J=6.5 Hz), 1.22-1.38 (4H, m), 1.41-1.62 (2H, m), 2.50-2.59
(1H, m), 2.66 (1H, dd, J=6.0, 13.5 Hz), 2.82 (1H, dd, J=8.5, 13.5
Hz), 2.86 (6H, s), 3.78 (2H, t, J=5.5 Hz), 4.15 (2H, t, J=5.5 Hz),
4.33 (2H, s), 6.87 (2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.60
(2H, d, J=8.5 Hz), 7.76 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz),
7.93 (2H, d, J=8.5 Hz).
EXAMPLE 30
2-Butyl-3-[4-[2-(4'-carboxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-210 compound)
[0846] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4'-methoxycarbonylbiphenyl-4-carbonylamino)ethoxy]phenyl-
]propionate (243 mg), which is the product of Reference example 12,
was reacted with aqueous sodium hydroxide solution (1N, 1.83 ml)
and the reaction mixture was treated to give the title compound
(163 mg) as a white powder.
[0847] mp 199-201.degree. C.
[0848] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 0.83 (3H, t, J=6.5 Hz), 1.18-1.31 (4H, m), 1.37-1.52
(2H, m), 2.40-2.50 (1H, m), 2.61 (1H, dd, J=6.0, 13.5 Hz), 2.74
(1H, dd, J=8.5, 13.5 Hz), 3.66 (2H, t, J=5.5 Hz), 4.10 (2H, t,
J=5.5 Hz), 6.87 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.85
(2H, d, J=8.0 Hz), 7.87 (2H, d, J=8.0 Hz), 7.99 (2H, d, J=8.5 Hz),
8.05 (2H, dd, J=2.5, 8.5 Hz), 8.78 (1H, d, J=5.5 Hz).
EXAMPLE 31
Ethyl
2-butyl-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-212 compound)
[0849] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (620 mg), which is
the product of Reference example 6, 3'-methoxybiphenyl-4-carboxylic
acid (456 mg) and carbonyldiimidazole (389 mg) and the reaction
mixture was treated to give the title compound (740 mg) as a
colorless oil.
[0850] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.31 (4H, m), 1.41-1.68
(2H, m), 2.53-2.64 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.87 (3H, s), 3.88 (2H, q, J=5.0 Hz),
4.05 (2H, q, J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.62 (1H, t, J=5.0
Hz), 6.84 (2H, d, J=8.5 Hz), 6.92-6.95 (1H, m), 7.09 (2H, d, J=8.5
Hz), 7.11-7.14 (1H, m), 7.18-7.21 (1H, m), 7.38 (1H, t, J=8.0 Hz),
7.65 (2H, d, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz).
EXAMPLE 32
2-Butyl-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-212 compound)
[0851] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (730 mg), which is the product of Example 31, was reacted with
aqueous sodium hydroxide solution (1N, 4.50 ml) and the reaction
mixture was treated to give the title compound (520 mg) as a white
powder.
[0852] mp 107-109.degree. C.
[0853] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.21-1.38 (4H, m), 1.45-1.71 (2H, m), 2.58-2.67 (1H, m),
2.71 (1H, dd, J=6.5, 13.5 Hz), 2.90 (1H, dd, J=8.5, 13.5 Hz),
3.83-3.90 (5H, m), 4.13 (2H, t, J=5.0 Hz), 6.71 (1H, t, J=5.0 Hz),
6.83 (2H, d, J=8.5 Hz), 6.93 (1H, dd, J=2.5, 8.0 Hz), 7.10 (2H, d,
J=8.5 Hz), 7.12 (1H, d, J=2.5 Hz), 7.18 (2H, d, J=8.0 Hz), 7.37
(1H, t, J=8.0 Hz), 7.64 (2H, d, J=8.5 Hz), 7.85 (2H, d, J=8.5
Hz).
EXAMPLE 33
Ethyl 2-butyl-3-[4-[2-(3
'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]p- ropionate (ethyl
ester of exemplification No. 4-213 compound)
[0854] In a similar manner to that described in Example 25, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (678 mg), which is
the product of Reference example 6, 3'-hydroxybiphenyl-4-carboxylic
acid (450 mg), which is the product of Reference example 13,
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (443
mg) and 1-hydroxybenzotriazole monohydrate (354 mg) and the
reaction mixture was treated to give the title compound (291 mg) as
a white powder.
[0855] mp 76-77.5.degree. C.
[0856] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.36 (4H, m), 1.40-1.69
(2H, m), 2.52-2.65 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.89 (2H, q, J=5.0 Hz), 4.06 (2H, q,
J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz), 6.10 (1H, s), 6.70 (1H, t, J=5.0
Hz), 6.83 (2H, d, J=8.5 Hz), 6.83-6.91 (1H, m), 7.08 (2H, d, J=8.5
Hz), 7.09-7.16 (2H, m), 7.31 (1H, t, J=8.0 Hz), 7.58 (2H, d, J=8.5
Hz), 7.83 (2H, d, J=8.5 Hz).
EXAMPLE 34
2-Butyl-3-[4-[2-(3'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-213 compound)
[0857] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(3'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (350 mg), which is the product of Example 33, was reacted with
aqueous sodium hydroxide solution (1N, 2.85 ml) and the reaction
mixture was treated to give the title compound (290 mg) as a white
powder.
[0858] mp 98-100.degree. C.
[0859] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.84-0.89
(3H, m), 1.21-1.40 (4H, m), 1.45-1.68 (2H, m), 2.51-2.90 (3H, m),
3.80-3.88 (2H, m), 4.12-4.20 (2H, m), 6.82-6.92 (3H, m), 7.04-7.15
(4H, m), 7.27 (1H, t, J=8.0 Hz), 7.55-7.70 (3H, m), 7.90 (2H, d,
J=8.0 Hz), 8.91-9.08 (1H, brs).
EXAMPLE 35
2-Butyl-3-[4-[2-(3'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-214 compound)
[0860] In a similar manner to that described in Example 27, ethyl
2-butyl-3-[4-[2-(3'-dimethoxymethylbiphenyl-4-carbonylamino)ethoxy]phenyl-
]propionate (1.46 g), which is the product of Reference example 14,
was reacted with aqueous sodium hydroxide solution (1N, 5.40 ml)
and the reaction mixture was treated to give
2-butyl-3-[4-[2-(3'-dimethoxymethylb-
iphenyl-4-carbonylamino)ethoxy]phenyl]propionic acid (1.39 g) as a
syrup. This compound (365 mg) was reacted and the reaction mixture
was treated in a similar manner to that described in Example 27 to
give the title compound (335 mg) as a yellowish brown solid.
[0861] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.88 (3H, t,
J=6.5 Hz), 1.18-1.38 (4H, m), 1.40-1.78 (2H, m), 2.61-2.68 (1H, m),
2.73 (1H, dd, J=6.5, 13.5 Hz), 2.92 (1H, dd, J=8.0, 13.5 Hz), 3.89
(2H, q, J=5.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.69 (1H, brt), 6.85
(2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz), 7.64 (1H, t, J=8.0 Hz),
7.69 (2H, d, J=8.5 Hz), 7.86-7.91 (2H, m), 7.89 (2H, d, J=8.5 Hz),
8.12 (1H, s), 10.10 (1H, s).
EXAMPLE 36
Sodium
2-butyl-3-[4-[2-(3'-hydroxymethylbiphenyl-4-carbonylamino)ethoxy]ph-
enyl]propionic acid (exemplification No. 4-218 compound)
[0862] A dioxane solution of hydrogen chloride (4N, 1.2 ml) was
added to a suspension of sodium
2-butyl-3-[4-[2-(3'-methoxymethoxymethylbiphenyl-4-c-
arbonylamino)ethoxy]phenyl]propionate (238 mg), which is the
product of Reference example 15, in ethanol (20 ml) at ambient
temperature. The mixture was allowed to stand overnight. At the end
of this time the reaction mixture was concentrated under reduced
pressure. The residue was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and washed with
saturated aqueous sodium chloride solution and dried over anhydrous
magesium sulfate and then concentrated under reduced pressure. The
residue was purified via chromatography on a silica gel column
using dichloromethane/methanol=20/1-10/1 as the eluant to give the
free acid. The title compound (140 mg)was obtained by reaction of
the free acid with sodium hydroxide as a yellowish brown solid.
[0863] mp 124-126.degree. C.
[0864] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 0.87
(3H, t, J=7.0 Hz), 1.18-1.39 (4H, m), 1.44-1.63 (2H, m), 2.32-2.47
(1H, m), 2.51 (1H, dd, J=7.0, 13.5 Hz), 2.85 (1H, dd, J=6.0, 13.5
Hz), 3.76 (2H, t, J=5.5 Hz), 4.14 (2H, t, J=5.5 Hz), 4.68 (2H, s),
6.84 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 7.36 (1H, d, J=7.5
Hz), 7.44 (1H, t, J=7.5 Hz), 7.56 (1H, d, J=7.5 Hz), 7.66 (1H, s),
7.72 (2H, d, J=8.5 Hz), 7.90 (2H, d, J=8.5 Hz).
EXAMPLE 37
Ethyl
2-butyl-3-[4-[2-(3'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 4-214 compound)
[0865] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (683 mg), which is
the product of Reference example 6, 3'-formylbiphenyl-4-carboxylic
acid (635 mg) and carbonyldiimidazole (500 mg) and the reaction
mixture was treated to give the title compound (506 mg) as a pale
brown oil.
[0866] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.39 (4H, m), 1.41-1.73
(2H, m), 2.53-2.66 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.90 (2H, q, J=5.0 Hz), 4.06 (2H, q,
J=7.0 Hz), 4.16 (2H, t, J=5.0 Hz), 6.64 (1H, brt), 6.84 (2H, d,
J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.64 (1H, t, J=7.5 Hz), 7.70
(2H, d, J=8.5 Hz), 7.86-7.92 (2H, m), 7.90 (2H, d, J=8.5 Hz), 8.12
(1H, s), 10.10 (1H, s).
EXAMPLE 38
Ethyl
2-butyl-3-[4-[2-(3'-dimethylaminomethylbiphenyl-4-carbonylamino)etho-
xy]phenyl]propionate (ethyl ester of exemplification No. 4-215
compound)
[0867] In a similar manner to that described in Example 29, a
reaction was carried out using ethyl
2-butyl-3-[4-[2-(3'-formylbiphenyl-4-carbonylamin-
o)ethoxy]phenyl]propionate (415 mg), which is the product of
Example 37, triethylamine (0.23 ml), dimethylamine hydrochloride
(139 mg), titanium tetraisopropoxide (0.49 ml) and sodium
borohydride (56 mg) and then the reaction mixture was treated to
give the title compound (263 mg) as a colorless syrup.
[0868] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86(3H, t,
J=7.0Hz), 1.16(3H, t, J=7.0Hz), 1.20-1.37 (4H, m), 1.39-1.75 (2H,
m), 2.23 (6H, s), 2.55-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz),
2.86 (1H, dd, J=8.5, 13.5 Hz), 3.52 (2H, s), 3.89 (2H, q, J=5.0
Hz), 4.06 (2H, q, J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.63 (1H,
brt), 6.84 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.34 (1H, d,
J=7.5 Hz), 7.42 (1H, t, J=7.5 Hz), 7.52 (1H, d, J=7.5 Hz), 7.58
(1H, s), 7.68 (2H, d, J=8.5 Hz), 7.84 (2H, d, J=8.5 Hz).
EXAMPLE 39
2-Butyl-3-[4-[2-(3'-dimethylaminomethylbiphenyl-4-carbonylamino)ethoxy]phe-
nyl]propionic acid (exemplification No. 4-215 compound)
[0869] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(3'-dimethylaminomethylbiphenyl-4-carbonylamino)ethoxy]ph-
enyl]propionate (263 mg), which is the product of Example 38, was
reacted with aqueous sodium hydroxide solution (1N, 1.00 ml) and
the reaction mixture was treated to give the title compound (121
mg) as a white powder.
[0870] mp 95-97.degree. C.
[0871] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 0.86
(3H, t, J=7.0 Hz), 1.14-1.34 (4H, m), 1.35-1.61 (2H, m), 2.46-2.57
(1H, m), 2.62 (1H, dd, J=6.5, 13.5 Hz), 2.77 (6H, s), 2.81 (1H, dd,
J=8.5, 13.5 Hz), 3.76 (2H, t, J=5.5 Hz), 4.15 (2H, t, J=5.5 Hz),
4.25 (2H, s), 6.86 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.49
(1H, d, J=7.5 Hz), 7.57 (1H, t, J=7.5 Hz), 7.74-7.79 (1H, m), 7.75
(2H, d, J=8.5 Hz), 7.82 (1H, s), 7.91 (2H, d, J=8.5 Hz).
EXAMPLE 40
Ethyl
2-butyl-3-[4-[2-(3'-carboxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-217 compound)
[0872] Sodium dihydrogenphosphate dihydrate (24 mg) and water (0.3
ml) was added to a solution of ethyl
2-butyl-3-[4-[2-(3'-formylbiphenyl-4-carbony-
lamino)ethoxy]phenyl]propionate (390 mg), which is the product of
Example 37, in acetonitrile (6 ml). Aqueous hydrogen peroxide
solution (30%, 0.12 ml) and an aqueous solution (0.3 ml) of sodium
chlorite (104 mg) was added to the mixture in an ice bath. The
mixture was stirred for 1 hour in an ice bath and then stirred for
2.5 hours at ambient temperature. After this, the reaction was
quenched with sodium thiosulfate and the reaction mixture was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
chloride and dried over anhydrous magnesium sulfate and then
concentrated under reduced pressure. Diisopropyl ether was added to
the residue to give the title compound (217 mg) as a white
solid.
[0873] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=6.5 Hz), 1.15 (3H, t, J=7.0 Hz), 1.20-1.39 (4H, m), 1.40-1.51
(1H, m), 1.53-1.68 (1H, m), 2.51-2.63 (1H, m), 2.68 (1H, dd, J=6.5,
13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.83-3.95 (2H, m), 4.05
(2H, q, J=7.0 Hz), 4.12-4.20 (2H, m), 6.70 (1H, brt), 6.84 (2H, d,
J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.53-7.61 (1H, m), 7.63-7.77
(2H, m), 7.79-7.94 (3H, m), 8.08-8.19 (1H, m), 8.36 (1H, s).
EXAMPLE 41
2-Butyl-3-[4-[2-(3'-carboxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-217 compound)
[0874] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(3'-carboxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (273 mg), which is the product of Example 40, was reacted with
aqueous sodium hydroxide solution (1N, 1.10 ml) and the reaction
mixture was treated to give the title compound (196 mg) as
colorless crystals.
[0875] mp 142-143.degree. C.
[0876] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 0.87
(3H, t, J=7.0 Hz), 1.20-1.44 (4H, m), 1.44-1.65 (2H, m), 2.49-2.60
(1H, m), 2.66 (1H, dd, J=6.0, 13.5 Hz), 2.82 (1H, dd, J=8.5, 13.5
Hz), 3.77 (2H, q, J=5.5 Hz), 4.15 (2H, t, J=5.5 Hz), 6.87 (2H, d,
J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.58 (1H, t, J=7.5 Hz), 7.75
(2H, d, J=8.5 Hz), 7.90 (1H, d, J=7.5 Hz), 7.93 (2H, d, J=8.5 Hz),
8.04 (1H, d, J=7.5 Hz), 8.30 (1H, s), 8.72 (1H, brt).
EXAMPLE 42
Ethyl
2-butyl-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-219 compound)
[0877] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (643 mg), which is
the product of Reference example 6, 2'-methoxybiphenyl-4-carboxylic
acid (500 mg) and carbonyldiimidazole (426 mg) and the reaction
mixture was treated to give the title compound (750 mg) as a pale
yellow oil.
[0878] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.91 (3H, t,
J=6.5 Hz), 1.20 (3H, t, J=7.0 Hz), 1.28-1.40 (4H, m), 1.45-1.73
(2H, m), 2.59-2.79 (2H, m), 2.85-2.97 (1H, ), 3.86 (3H, s), 3.93
(2H, q, J=5.0 Hz), 4.10 (2H, q, J=7.0 Hz), 4.18 (2H, t, J=5.0 Hz),
6.67 (1H, t, J=5.0 Hz), 6.86 (2H, d, J=8.5 Hz), 7.06 (2H, t, J=8.0
Hz), 7.13 (2H, d, J=8.5 Hz), 7.35-7.44 (2H, m), 7.65 (2H, d, J=8.0
Hz), 7.86 (2H, d, J=8.0 Hz).
EXAMPLE 43
2-Butyl-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propioni-
c acid (exemplification No. 4-219 compound)
[0879] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (750 mg), which is the product of Example 42, was reacted with
aqueous sodium hydroxide solution (1N, 5.00 ml) and the reaction
mixture was treated to give the title compound (625 mg) as a pale
orange powder.
[0880] mp 190-192.degree. C.
[0881] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.21-1.38 (4H, m), 1.43-1.71 (2H, m), 2.58-2.78 (2H, m),
2.85-2.97 (1H, m), 3.80 (3H, s), 3.87 (2H, q, J=5.0 Hz), 4.13 (2H,
t, J=5.0 Hz), 6.67 (1H, t, J=5.0 Hz), 6.83 (2H, d, J=8.5 Hz),
6.98-7.06 (2H, m), 7.10 (2H, d, J=8.5 Hz), 7.28-7.38 (2H, m), 7.59
(2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz).
EXAMPLE 44
Ethyl
2-butyl-3-[4-[2-(2'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]pr-
opionate (ethyl ester of exemplification No. 4-220 compound)
[0882] In a similar manner to that described in Example 25, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (249 mg), which is
the product of Reference example 6, 2'-hydroxybiphenyl-4-carboxylic
acid (200 mg), which is the product of Reference example 16,
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (195
mg) and 1-hydroxybenzotriazole monohydrate (138 mg) and the
reaction mixture was treated to give the title compound (386 mg) as
a colorless oil.
[0883] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=6.5 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.32 (4H, m), 1.40-1.69
(2H, m), 2.53-2.72 (2H, m), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.89
(2H, q, J=5.0 Hz), 4.01-4.18 (4H, m), 5.27 (1H, s), 6.61-6.69 (1H,
m), 6.83 (2H, d, J=8.5 Hz), 6.95-7.11 (4H, m), 7.21-7.28 (2H, m),
7.58 (2H, d, J=8.0 Hz), 7.88 (2H, d, J=8.0 Hz).
EXAMPLE 45
Sodium
2-butyl-3-[4-[2-(2'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]p-
ropionate (exemplification No. 4-220 compound)
[0884] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2'-hydroxybiphenyl-4-carbonylamino)ethoxy]phenyl]propion-
ate (345 mg), which is the product of Example 44, was reacted with
aqueous sodium hydroxide solution (1N, 2.82 ml) and the reaction
mixture was treated to afford the crude free acid which was
subjected to chromatography on a silica gel thin layer plate using
dichloromethane/methanol=10/1 as the eluant. The product was
converted to the sodium salt to give the title compound (200 mg) as
colorless crystals.
[0885] mp 153-156.degree. C.
[0886] .sup.1H-NMR of the free acid (270 MHz, CDCl.sub.3): .delta.
ppm 0.88 (3H, t, J=7.0 Hz), 1.25-1.37 (4H, m), 1.44-1.71 (2H, m),
2.55-2.78 (2H, m), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.83 (2H, q,
J=5.0 Hz), 4.10 (2H, t, J=5.0 Hz), 6.69-6.79 (1H, m), 6.80 (2H, d,
J=8.5 Hz), 6.95-7.10 (4H, m), 7.22-7.30 (2H, m), 7.55 (2H, d, J=8.0
Hz), 7.80 (2H, d, J=8.5 Hz).
EXAMPLE 46
Ethyl
2-butyl-3-[4-[2-(2'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 4-221 compound)
[0887] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (414 mg), which is
the product of Reference example 6, 2'-formylbiphenyl-4-carboxylic
acid (350 mg) and carbonyldiimidazole (296 mg) and the reaction
mixture was treated to give the title compound (314 mg) as a
colorless oil.
[0888] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.19-1.33 (4H, m), 1.41-1.68
(2H, m), 2.53-2.72 (2H, m), 2.87 (1H, dd, J=8.5, 13.5 Hz), 3.91
(2H, q, J=5.0 Hz), 4.01-4.20 (4H, m), 6.65-6.72 (1H, m), 6.84 (2H,
d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.42-7.59 (4H, m), 7.63-7.70
(1H, m), 7.89 (2H, d, J=8.0 Hz), 8.04 (1H, d, J=7.5 Hz), 9.96 (1H,
s).
EXAMPLE 47
2-Butyl-3-[4-[2-(2'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-221 compound)
[0889] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2'-formylbiphenyl-4-carbonylamino)ethoxy]phenyl]propiona-
te (314 mg), which is the product of Example 46, was reacted with
aqueous sodium hydroxide solution (1N, 2.50 ml) and the reaction
mixture was treated to afford the crude free acid which was
subjected to chromatography on a silica gel thin layer plate using
dichloromethane/methanol=10/1 as the eluant to give the title
compound (152 mg) as a mass of foam.
[0890] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.22-1.40 (4H, m), 1.42-1.70 (2H, m), 2.55-2.78 (2H, m),
2.88 (1H, dd, J=8.5, 13.5 Hz), 3.83-3.93 (2H,m), 4.07-4.18 (2H, m),
6.81 (2H, d, J=8.0 Hz), 6.95-7.06 (1H, m), 7.09 (2H, d, J=8.5 Hz),
7.38-7.46 (3H, m), 7.48-7.56 (1H, m), 7.61-7.69 (1H, m), 7.89 (2H,
d, J=8.0 Hz), 8.02 (1H, d, J=7.5 Hz), 9.92 (1H, s).
EXAMPLE 48
Sodium
2-butyl-3-[4-[2-(4'-hydroxy-3',5'-dimethylbiphenyl-4-carbonylamino)-
ethoxy]phenyl]propionate (exemplification No. 4-205 compound)
[0891] In a similar manner to that described in Example 36,
2-butyl-3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carbonylamino-
)ethoxy]phenyl]propionic acid (1.00 g), which is the product of
Reference example 17, was reacted with a dioxane solution of
hydrogen chloride (4N, 0.69 ml) and the reaction mixture was
treated to give the title compound (528 mg) as a pale brown
solid.
[0892] mp 137-139.degree. C.
[0893] .sup.1H-NMR (270 MHz, a mixture of CDCl.sub.3 and deuterated
methanol (10/3)): .delta. ppm 0.85 (3H, t, J=7.0 Hz), 1.20-1.40
(5H, m), 1.43-1.60 (1H, m), 2.27 (6H, s), 2.34-2.47 (1H, m), 2.52
(1H, dd, J=7.5, 13.5 Hz), 2.85 (1H, dd, J=7.5, 13.5 Hz), 3.74 (2H,
t, J=5.5 Hz), 4.13(2H, t, J=5.5 Hz), 6.84 (2H, d, J=8.5 Hz), 7.12
(2H, d, J=8.5 Hz), 7.62 (2H, d, J=8.5 Hz), 7.84 (2H, d, J=8.5
Hz).
EXAMPLE 49
Ethyl-2-butyl-3-[4-[2-(2-hydroxypyridine-5-carbonylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 4-193 compound)
[0894] In a similar manner to that described in Example 25, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (843 mg), which is
the product of Reference example 6, 6-hydroxynicotinic acid (400
mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
(660 mg) and 1-hydroxybenzotriazole monohydrate (528 mg) and the
reaction mixture was treated to give the title compound (636 mg) as
a white powder.
[0895] mp 102-104.degree. C.
[0896] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.17 (3H, t, J=7.0 Hz), 1.21-1.32 (4H, m), 1.40-1.70
(2H, m), 2.53-2.72 (2H, m), 2.80-2.91 (1H, m), 3.81 (2H, q, J=5.0
Hz), 4.02-4.12 (4H, m), 6.42-6.52 (1H, m), 6.56 (1H, d, J=9.5 Hz),
6.81 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.80 (1H, dd,
J=2.5, 9.5 Hz), 8.00 (1H, d, J=2.5 Hz).
EXAMPLE 50
2-Butyl-3-[4-[2-(2-hydroxypyridine-5-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-193 compound)
[0897] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2-hydroxypyridine-5-carbonylamino)ethoxy]phenyl]propiona-
te (300 mg), which is the product of Example 49, was reacted with
aqueous sodium hydroxide solution (1N, 3.00 ml) and the reaction
mixture was treated to give the title compound (240 mg) as a pale
yellow powder.
[0898] mp 69-71.degree. C.
[0899] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.30-1.45 (4H, m), 1.50-1.79 (2H, m), 2.57-2.68 (1H, m),
2.77 (1H d, J=7.5 Hz), 3.68-3.77 (2H, m), 4.00-4.09 (2H, m), 6.42
(1H, d, J=10.0 Hz), 6.71 (2H, d, J=8.5 Hz), 7.05 (2H, d, J=8.5 Hz),
7.10-7.20 (1H, m), 7.75-7.80 (2H, m).
EXAMPLE 51
Ethyl
2-butyl-3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 4-96 compound)
[0900] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (766 mg), which is
the product of Reference example 6, 6-methoxynicotinic acid (400
mg) and carbonyldiimidazole (508 mg) and the reaction mixture was
treated to give the title compound (783 mg) as colorless
crystals.
[0901] mp 129-130.degree. C.
[0902] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87(3H, t,
J=7.0Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.33 (4H, m), 1.40-1.70 (2H,
m), 2.52-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86 (1H, dd,
J=8.5, 13.5 Hz), 3.85 (2H, q, J=5.0 Hz), 4.00 (3H, s), 4.06 (2H, q,
J=7.0 Hz), 4.12 (2H, t, J=5.0 Hz), 6.46-6.55 (1H, m), 6.78 (1H, d,
J=8.5 Hz), 6.82 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.99
(1H, dd, J=2.5, 8.5 Hz), 8.59 (1H, d, J=2.5 Hz).
EXAMPLE 52
2-Butyl-3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-96 compound)
[0903] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]phenyl]propiona-
te (500 mg), which is the product of Example 51, was reacted with
aqueous sodium hydroxide solution (1N, 4.00 ml) and the reaction
mixture was treated to give the title compound (293 mg) as a white
powder.
[0904] mp 144-145.degree. C.
[0905] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.24-1.40 (4H, m), 1.47-1.75 (2H, m), 2.62-2.90 (3H, m),
3.71-3.97 (2H, m), 3.98 (3H, s), 4.11-4.26 (2H, m), 6.48-6.60 (1H,
m), 6.78 (1H, d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz), 7.11 (2H, d,
J=8.5 Hz), 8.03 (1H, dd, J=2.5, 8.5 Hz), 8.31 (1H, d, J=2.5
Hz).
EXAMPLE 53
Ethyl
2-butyl-3-[4-[2-(2-isopropoxypyridine-5-carbonylamino)ethoxy]phenyl]-
propionate (ethyl ester of exemplification No. 4-98 compound)
[0906] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (156 mg), which is
the product of Reference example 6, 6-isopropoxynicotinic acid (106
mg), which is the product of Reference example 18, and
carbonyldiimidazole (112 mg) and the reaction mixture was treated
to give the title compound (170 mg) as a colorless oil.
[0907] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.20-1.40 (10H, m), 1.41-1.71
(2H, m), 2.61-2.73 (2H, m), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.83
(2H, q, J=5.0 Hz), 4.05 (2H, q, J=7.0 Hz), 4.11 (2H, t, J=5.0 Hz),
5.35 (2H, septet, J=6.0 Hz), 6.56-6.62 (1H, m), 6.69 (1H, d, J=8.5
Hz), 6.81 (2H, d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz), 7.97 (1H, dd,
J=2.5, 8.5 Hz), 8.58 (1H, d, J=2.5 Hz).
EXAMPLE 54
2-Butyl-3-[4-[2-(2-isopropoxypyridine-5-carbonylamino)ethoxy]phenyl]propio-
nic acid (exemplification No. 4-98 compound)
[0908] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2-isopropoxypyridine-5-carbonylamino)ethoxy]phenyl]propi-
onate (170 mg), which is the product of Example 53, was reacted
with aqueous sodium hydroxide solution (1N, 0.75 ml) and the
reaction mixture was treated to give the title compound (137 mg) as
colorless crystals.
[0909] mp 117-118.degree. C.
[0910] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.22-1.40 (9H, m), 1.46-1.80 (3H, m), 2.59-2.82 (2H, m),
2.85 (1H, dd, J=9.0, 13.5 Hz), 3.73-3.96 (2H, m), 4.10-4.22 (2H,
m), 5.31 (2H, septet, J=6.0 Hz), 6.48-6.57 (1H, m), 6.70 (1H, d,
J=8.5 Hz), 6.84 (2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz), 8.00
(1H, dd, J=2.5, 8.5 Hz), 8.35 (1H, d, J=2.5 Hz).
EXAMPLE 55
Ethyl
2-butyl-3-[4-[2-(2-phenoxypyridine-5-carbonylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 4-106 compound)
[0911] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (158 mg), which is
the product of Reference example 6, 6-phenoxynicotinic acid (125
mg) and carbonyldiimidazole (112 mg) and the reaction mixture was
treated to give the title compound (225 mg) as a colorless oil.
[0912] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.20-1.36 (4H, m), 1.41-1.70
(2H, m), 2.52-2.72 (2H, m), 2.85 (1H, dd, J=8.5, 13.5 Hz),
3.78-3.89 (2H, m), 4.01-4.15 (4H, m), 6.65-6.82 (3H, m), 6.92 (1H,
d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz), 7.13 (2H, d, J=7.5 Hz),
7.20-7.26 (1H, m), 7.38-7.45 (2H, m), 8.12 (1H, dd, J=2.5 8.5 Hz),
8.58 (1H, d, J=2.5 Hz).
EXAMPLE 56
2-Butyl-3-[4-[2-(2-phenoxypyridine-5-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-106 compound)
[0913] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(2-phenoxypyridine-5-carbonylamino)ethoxy]phenyl]propiona-
te (215 mg), which is the product of Example 55, was reacted with
aqueous sodium hydroxide solution (1N, 1.32 ml) and the reaction
mixture was treated to afford the crude free acid which was
subjected to chromatography on a silica gel thin layer plate using
dichloromethane/methanol=10/1 as the eluant to give the title
compound (137 mg) as colorless crystals.
[0914] mp 124-125.degree. C.
[0915] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.85-0.95
(3H, m), 1.25-1.39 (4H, m), 1.40-1.71 (2H, m), 2.53-2.88 (3H, m),
3.70-3.97 (2H, m), 4.08-4.28 (2H, m), 6.58-6.68 (1H, m), 6.81 (2H,
d, J=8.5 Hz), 6.93 (1H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.13
(2H, d, J=8.5 Hz), 7.20-7.29 (1H, m), 7.39-7.48 (2H, m), 8.15 (1H,
dd, J=8.5 Hz), 8.29 (1H, s).
EXAMPLE 57
Ethyl
2-butyl-3-[4-[2-(quinoline-3-carbonylamino)ethoxy]phenyl]propionate
(ethyl ester of exemplification No. 4-150 compound)
[0916] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (529 mg), which is
the product of Reference example 6, quinoline-3-carboxylic acid
(312 mg) and carbonyldiimidazole (350 mg) and the reaction mixture
was treated to give the title compound (760 mg) as a yellow
oil.
[0917] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=6.5 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.37 (4H, m), 1.40-1.70
(2H, m), 2.55-2.63 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.95 (2H, q, J=5.0 Hz), 4.06 (2H, q,
J=7.0 Hz), 4.19 (2H, t, J=5.0 Hz), 6.76-6.82 (1H, m), 6.85 (2H, d,
J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.63 (1H, t, J=8.0 Hz),
7.78-7.85 (1H, m) 7.92 (1H, d, J=8.0 Hz), 8.16 (1H, d, J=8.0 Hz),
8.60 (1H, d, J=2.5 Hz), 9.28 (1H, d, J=2.5 Hz).
EXAMPLE 58
Sodium
2-butyl-3-[4-[2-(quinoline-3-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-150 compound)
[0918] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(quinoline-3-carbonylamino)ethoxy]phenyl]propionate
(760 mg), which is the product of Example 57, was reacted with
aqueous sodium hydroxide solution (1N, 6.00 ml) and the reaction
mixture was treated to give the title compound (386 mg) as a white
powder.
[0919] mp 245-248.degree. C.
[0920] .sup.1H-NMR of the free acid (270 MHz, CDCl.sub.3): .delta.
ppm 0.90 (3H, t, J=7.0 Hz), 1.28-1.48 (4H, m), 1.50-1.80 (2H, m),
2.58-2.90 (3H, m), 3.80-4.07 (2H, m), 4.20-4.39 (2H, m), 6.68-6.84
(1H, m), 6.87 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 7.62 (1H,
t, J=8.0 Hz), 7.81 (1H, t, J=8.0 Hz), 7.91 (1H, d, J=8.0 Hz), 8.13
(1H, d, J=8.0 Hz), 8.70 (1H, s), 8.81 (1H, s).
EXAMPLE 59
Ethyl
2-butyl-3-[4-[2-(indole-3-carbonylamino)ethoxy]phenyl]propionate
(ethyl ester of exemplification No. 4-143 compound)
[0921] In a similar manner to that described in Example 25, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (546 mg), which is
the product of Reference example 6, indole-3-carboxylic acid (300
mg), 1-(3-dimethylaminopropyl)-3-ethylcarbo- diimide hydrochloride
(428 mg) and 1-hydroxybenzotriazole monohydrate (342 mg)and the
reaction mixture was treated to give the title compound (650 mg) as
a yellow oil.
[0922] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.22-1.32 (4H, m), 1.40-1.68
(2H, m), 2.55-2.64 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.91 (2H, q, J=5.0 Hz), 4.05 (2H, q,
J=7.0 Hz), 4.17 (2H, t, J=5.0 Hz), 6.44 (1H, t, J=5.0 Hz), 6.86
(2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.24-7.29 (2H, m),
7.41-7.45 (1H, m), 7.74 (1H, d, J=3.0 Hz), 7.95-7.99 (1H, m),
8.59-8.70 (1H, m).
EXAMPLE 60
2-Butyl-3-[4-[2-(indole-3-carbonylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-143 compound)
[0923] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(indole-3-carbonylamino)ethoxy]phenyl]propionate
(650 mg), which is the product of Example 59, was reacted with
aqueous sodium hydroxide solution (1N, 5.00 ml) and the reaction
mixture was treated to give the title compound (500 mg) as a white
powder.
[0924] mp 171-173.degree. C.
[0925] .sup.1H-NMR of the free acid (270 MHz, CDCl.sub.3): .delta.
ppm 0.86 (3H, t, J=7.0 Hz), 1.22-1.37 (4H, m), 1.40-1.68 (2H, m),
2.40-2.62 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.90 (1H, dd,
J=8.5, 13.5 Hz), 3.88 (2H, q, J=5.0 Hz), 4.17 (2H, t, J=5.0 Hz),
6.73 (1H, t, J=5.0 Hz), 6.85 (2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5
Hz), 7.17-7.24 (2H, m), 7.42-7.47 (1H, m), 7.78 (1H, d, J=3.0 Hz),
8.00-8.05 (1H, m).
EXAMPLE 61
Ethyl
2-butyl-3-[4-[2-(4-N,N-diethylaminobenzoylamino)ethoxy]phenyl]propio-
nate (ethyl ester of exemplification No. 4-230 compound)
[0926] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (455 mg), which is
the product of Reference example 6, 4-N,N-diethylaminobenzoic acid
(300 mg) and carbonyldiimidazole (302 mg) and the reaction mixture
was treated to give the title compound (346 mg) as a colorless
oil.
[0927] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.13-1.20 (9H, m), 1.24-1.37 (4H, m), 1.40-1.70 (2H, m),
2.53-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86 (1H, dd,
J=8.5, 13.5 Hz), 3.39 (4H, q, J=7.0 Hz), 3.83 (2H, q, J=5.5 Hz),
4.01-4.14 (4H, m), 6.40 (1H, t, J=5.5 Hz), 6.63 (2H, d, J=8.5 Hz),
6.82 (2H, d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz), 7.66 (2H, d, J=8.5
Hz).
EXAMPLE 62
2-Butyl-3-[4-[2-(4-N,N-dietylaminobenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-230 compound)
[0928] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4-N,N-diethylaminobenzoylamino)ethoxy]phenyl]propionate
(340 mg), which is the product of Example 61, was reacted with
aqueous sodium hydroxide solution (1N, 2.20 ml) and the reaction
mixture was treated to give the title compound (257 mg) as a white
powder.
[0929] mp 76-78.degree. C.
[0930] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.17 (6H, t, J=7.0 Hz), 1.11-1.21 (4H, m), 1.45-1.70
(2H, m), 2.57-2.65 (1H, m), 2.70 (1H, dd, J=6.5, 13.5 Hz), 2.90
(1H, dd, J=8.0, 13.5 Hz), 3.38 (4H, q, J=7.0 Hz), 3.80 (2H, q,
J=5.0 Hz), 4.08 (2H, t, J=5.0 Hz), 6.48 (1H, t, J=5.0 Hz), 6.62
(2H, d, J=8.5 Hz), 6.82 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz),
7.65 (2H, d, J=8.5 Hz).
EXAMPLE 63
Ethyl
2-butyl-3-[4-[2-(4-piperidine-1-ylbenzoylamino)ethoxy]phenyl]propion-
ate (ethyl ester of exemplification No. 4-229 compound)
[0931] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (428 mg), which is
the product of Reference example 6, 4-piperidine-1-ylbenzoic acid
(300 mg) and carbonyldiimidazole (284 mg) and the reaction mixture
was treated to give the title compound (420 mg) as a white
powder.
[0932] mp 87-89.degree. C.
[0933] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.20-1.37 (4H, m), 1.40-1.73
(8H, m), 2.52-2.61 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.26-3.33 (4H, m), 3.83 (2H, q, J=5.0
Hz), 4.01-4.16 (4H, m), 6.48 (1H, t, J=5.0 Hz), 6.82 (2H, d, J=8.5
Hz), 6.87 (2H, d, J=9.0 Hz), 7.07 (2H, d, J=8.5 Hz), 7.67 (2H, d,
J=9.0 Hz).
EXAMPLE 64
2-Butyl-3-[4-[2-(4-piperidine-1-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 4-229 compound)
[0934] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(4-piperidine-1-ylbenzoylamino)ethoxy]phenyl]propionate
(370 mg), which is the product of Example 63, was reacted with
aqueous sodium hydroxide solution (1N, 2.30 ml) and the reaction
mixture was treated to give the title compound (324 mg) as a white
powder.
[0935] mp 112.5-114.degree. C.
[0936] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=6.5 Hz), 1.28-1.44 (4H, m), 1.48-1.77 (8H, m), 2.61-2.69 (1H, m),
2.73 (1H, dd, J=6.5, 13.5 Hz), 2.92 (1H, dd, J=8.0, 13.5 Hz),
3.27-3.33 (4H, m), 3.84 (2H, q, J=5.0 Hz), 4.11 (2H, t, J=5.0 Hz),
6.54 (1H, t, J=5.0 Hz), 6.84 (2H, d, J=8.5 Hz), 6.89 (2H, d, J=9.0
Hz), 7.12 (2H, d, J=8.5 Hz), 7.70 (2H, d, J=9.0 Hz).
EXAMPLE 65
Ethyl
2-butyl-3-[4-[2-(N-(3-phenylpropyl)-(4-pyridine-2-ylbenzoyl)amino)et-
hoxy]phenyl]propionate (ethyl ester of exemplification No. 20-71
compound)
[0937] Triethylamine (0.37 ml) was added to a solution of ethyl
2-butyl-3-[4-[2-(3-phenylpropylamino)ethoxy]phenyl]propionate (460
mg), which is the product of Reference example 19, and
4-pyridine-2-ylbenzoylc- hloride hydrochloride (341 mg) in
dichloromethane (10 ml) at ambient temperature. After the mixture
was stirred for 5 hours at ambient temperature, the solvent was
distilled off under reduced pressure. The residue was partitioned
between ethyl acetate and water and the ethyl acetate layer was
separated and dried over anhydrous magnesium sulfate and then
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using
dichloromethane/methanol=- 19/1 as the eluant to give the title
compound (275 mg) as a colorless oil.
[0938] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.12-2.05 (l 1H, m), 2.42-2.91 (5H, m), 3.35-4.30 (8H,
m), 6.70-6.88 (2H, m), 7.00-7.60 (10H, m), 7.73-7.85 (2H, m),
7.99-8.06 (2H, m), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 66
2-Butyl-3-[4-[2-(N-(3-phenylpropyl)-(4-pyridine-2-ylbenzoyl)amino)ethoxy]p-
henyl]propionic acid hydrochloride (exemplification No. 20-71
compound)
[0939] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-(N-(3-phenylpropyl)-(4-pyridine-2-ylbenzoyl)amino)ethoxy]-
phenyl]propionate (275 mg), which is the product of Example 65, was
reacted with aqueous sodium hydroxide solution (1N, 1.00 ml) and
the reaction mixture was treated. The title compound (230 mg) was
obtained as a mass of foam by treating the product with a dioxane
solution of hydrogen chloride (4N).
[0940] .sup.1H-NMR of free acid (270 MHz. CDCl.sub.3): .delta. ppm
0.92 (3H, t, J=7.0 Hz), 1.30-1.45 (4H, m), 1.50-2.10 (4H. m),
2.55-2.82 (5H, m), 3.48-3.83 (4H, m), 4.00-4.36 (2H. m), 6.57-6.86
(2H, m), 7.02-7.39 (10H, m), 7.68-7.89 (4H, m), 8.69 (1H, d, J=5.0
Hz).
EXAMPLE 67
Ethyl
2-butyl-3-[4-[2-[N-butyl-(4-pyridine-2-ylbenzoyl)amino]ethoxy]phenyl-
]propionate (ethyl ester of exemplification No. 20-53 compound)
[0941] In a similar manner to that described in Example 65, a
reaction was carried out using ethyl
2-butyl-3-[4-[2-(butylamino)ethoxy]phenyl]propion- ate (390 mg),
which is the product of Reference example 20,
4-pyridine-2-ylbenzoylchloride hydrochloride (340 mg) and
triethylamine (0.37 ml) and the reaction mixture was treated to
give the title compound (165 mg) as a colorless oil.
[0942] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.78-1.71
(19H, m), 2.55-2.77 (2H, m), 2.82-2.91 (1H, m), 3.34-3.47 (1H, m),
3.65-3.80 (3H, m), 3.83-3.94 (1H, m), 4.06 (2H, q, J=7.0 Hz),
4.23-4.32 (1H, m), 6.68-6.91 (2H, m), 7.01-7.15 (2H, m), 7.23-7.30
(1H, m), 7.43-7.81 (4H, m), 8.02 (2H, d, J=8.5 Hz), 8.70 (0.6H, d,
J=5.0 Hz), 8.90 (0.4H, d, J=5.0 Hz).
EXAMPLE 68
2-Butyl-3-[4-[2-[N-butyl-(4-pyridine-2-ylbenzoyl)amino]ethoxy]phenyl]propi-
onic acid hydrochloride (exemplification No. 20-53 compound)
[0943] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[2-[N-butyl-(4-pyridine-2-ylbenzoyl)amino]ethoxy]phenyl]prop-
ionate (165 mg), which is the product of Example 67, was reacted
with aqueous sodium hydroxide solution (1N, 1.00 ml) and the
reaction mixture was treated. The title compound (110 mg) was
obtained as a mass of foam by treating the product with a dioxane
solution of hydrogen chloride (4N).
[0944] .sup.1H-NMR of free acid (270 MHz, CDCl.sub.3): .delta. ppm
0.80-1.01 (6H, m), 1.10-1.85 (10H, m), 2.60-2.85 (3H, m), 3.30-3.90
(4H, m), 4.11-4.38 (2H, m), 6.58-6.90 (2H, m), 7.02-7.14 (2H, m),
7.28-7.40 (3H, m), 7.68-7.90 (4H, m), 8.69 (1H, d, J=5.0 Hz).
EXAMPLE 69
Ethyl
2-butyl-3-[4-[3-(4-pyridine-2-ylbenzoylamino)propoxy]phenyl]propiona-
te (ethyl ester of exemplification No. 40-3 compound)
[0945] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(3-aminopropoxy)phenyl]-2-butylpropionate (500 mg), which is
the product of Reference example 21, 4-pyridine-2-ylbenzoic acid
(340 mg) and carbonyldiimidazole (333 mg) and the reaction mixture
was treated to give the title compound (178 mg) as a white
powder.
[0946] mp 110-112.degree. C.
[0947] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.33 (4H, m), 1.42-1.70
(2H, m), 2.14 (2H, quintuplet, J=6.0 Hz), 2.53-2.73 (2H, m),
2.80-2.91 (1H, m), 3.71 (2H, q, J=6.0 Hz), 4.06 (2H, q, J=7.0 Hz),
4.13 (2H, t, J=6.0 Hz), 6.76-6.80 (1H, m), 6.83 (2H, d, J=8.5 Hz),
7.10 (2H, d, J=8.5 Hz), 7.25-7.32 (1H, m), 7.76-7.81 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.73 (1H, d, J=5.0
Hz).
EXAMPLE 70
2-Butyl-3-[4-[3-(4-pyridine-2-ylbenzoylamino)propoxy]phenyl]propionic
acid (exemplification No. 40-3 compound)
[0948] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[3-(4-pyridine-2-ylbenzoylamino)propoxy]phenyl]propionate
(161 mg), which is the product of Example 69, was reacted with
aqueous sodium hydroxide solution (1N, 1.20 ml) and the reaction
mixture was treated to give the title compound (117 mg) as a white
powder.
[0949] mp 151-152.degree. C.
[0950] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.28-1.44 (4H, m), 1.51-1.64 (1H, m), 1.65-1.78 (1H, m),
2.15 (2H, quintuplet, J=6.0 Hz), 2.58-2.92 (3H, m), 3.60-3.80 (2H,
m), 4.15-4.21 (2H, m), 6.84 (2H, d, J=8.5 Hz), 6.87-6.95 (1H, m),
7.16 (2H, d, J=8.5 Hz), 7.30-7.35 (1H, m), 7.74-7.90 (6H, m), 8.69
(1H, d, J=5.5 Hz).
EXAMPLE 71
Ethyl
2-butyl-3-[4-[3-[N-methyl-(4-pyridine-2-ylbenzoyl)amino]propoxy]phen-
yl]propionate (ethyl ester of exemplification No. 20-80
compound)
[0951] In a similar manner to that described in Example 65, a
reaction was carried out using ethyl
2-butyl-3-[4-(3-methylaminopropoxy)phenyl]propion- ate (380 mg),
which is the product of Reference example 22,
4-pyridine-2-ylbenzoylchloride hydrochloride (360 mg) and
triethylamine (0.40 ml) and the reaction mixture was treated to
give the title compound (259 mg) as a white powder.
[0952] mp 58-60.degree. C.
[0953] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.20-1.38 (4H, m), 1.40-1.70
(2H, m), 1.96-2.23 (2H, m), 2.52-2.72 (2H, m), 2.80-2.91 (1H, m),
3.00-3.19 (3H,m), 3.49-3.60 (1H, m), 3.71-3.89 (2H, m), 4.00-4.12
(3H,m), 6.61-6.70 (1H, m), 6.79-6.89 (1H, m), 6.99-7.10 (2H, m),
7.23-7.28 (1H, m), 7.41-7.55 (2H, m), 7.70-7.81 (2H, m), 7.91-8.06
(2H, m), 8.71 (1H, d, J=5.0 Hz).
EXAMPLE 72
2-Butyl-3-[4-[3-[N-methyl-(4-pyridine-2-ylbenzoyl)amino]propoxy]phenyl]pro-
pionic acid (exemplification No. 20-80 compound)
[0954] In a similar manner to that described in Example 2, ethyl
2-butyl-3-[4-[3-[N-methyl-(4-pyridine-2-ylbenzoyl)amino]propoxy]phenyl]pr-
opionate (200 mg), which is the product of Example 71, was reacted
with aqueous sodium hydroxide solution (1N, 1.20 ml) and the
reaction mixture was treated to give the title compound (127 mg) as
a white powder.
[0955] mp 110-112.degree. C.
[0956] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.91 (3H, t,
J=7.0 Hz), 1.21-1.41 (4H, m), 1.48-1.61 (1H, m), 1.64-1.83 (1H, m),
1.93-2.23 (2H, m), 2.58-2.83 (3H, m), 3.00-3.17 (3H, m), 3.37-3.60
(1H, m), 3.68-4.26 (3H, m), 6.66-7.01 (2H, m), 7.10-7.30 (2H, m),
7.33-7.60 (3H, m), 7.70-8.20 (4H, m), 8.76-9.05 (1H, m).
EXAMPLE 73
Ethyl
2-propyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propiona-
te (ethyl ester of exemplification No. 3-35 compound)
[0957] A solution of ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-p- ropylpropionate
(2.20 g) in dioxane containing hydrogen chloride (4N, 30 ml) was
allowed to stand at ambient temperature for 40 minutes. At the end
of this time the reaction mixture was concentrated under reduced
pressure and the hydrogen chloride was azeotropically distilled off
with toluene to give a residue. A solution of diethyl
cyanophosphonate (0.97 ml) in N,N-dimethylformamide (4.0 ml) was
added to a solution of the residue obtained above (ethyl
3-[4-(2-aminoethoxy)phenyl]-2-propylpropion- ate hydrochloride),
4-pyridine-2-ylbenzoic acid (1.21 g) and triethylamine (1.80 ml) in
N,N-dimethylformamide (8.0 ml) in an ice bath. The mixture was
stirred for 1 hour in an ice bath and for 3 hours at ambient
temperature. The reaction mixture was partitioned between ethyl
acetate and water and the ethyl acetate was separated and washed
with saturated aqueous sodium hydrogencarbonate and dried over
anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was purified via chromatography on a silica
gel column using dichloroethane/ethyl acetate=7/3 as the eluant to
give the title compound (2.20 g) as a pale yellow powder.
[0958] mp 90.5-92.degree. C.
[0959] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.88 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.71 (4H, m), 2.50-2.72
(2H, m), 2.80-2.92 (1H, m), 3.81-3.95 (2H, m), 4.00-421 (4H, m),
6.60-6.71 (1H, m), 6.84 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz),
7.20-7.31 (1H, m), 7.70-7.80 (2H, m), 7.88 (2H, d, J=8.5 Hz), 8.07
(2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 74
2-Propyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 3-53 compound)
[0960] In a similar manner to that described in Example 2, ethyl
2-propyl-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(2.10 g), which is the product of Example 73, was reacted with
aqueous sodium hydroxide solution (1N, 15.0 ml) and the reaction
mixture was treated to give the title compound (1.96 g) as a white
powder.
[0961] mp 81-82.5.degree. C.
[0962] .sup.1H-NMR, (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.20-1.71 (4H, m), 2.55-2.75 (2H, m), 2.75-2.92 (1H, m),
3.74-3.90 (2H, m), 4.03-421 (2H, m), 6.71-6.89 (3H, m), 7.09 (2H,
d, J=8.5 Hz), 7.21-7.31 (1H, m), 7.66-7.83 (4H, m), 7.97 (2H, d,
J=8.5 Hz), 8.71 (1H, d, J=4.5 Hz).
EXAMPLE 75
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropionate
(ethyl ester of exemplification No. 6-15 compound)
[0963] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (666 mg), which is
the product of Reference example 4, biphenyl-4-carboxylic acid (400
mg) and carbonyldiimidazole (393 mg) and the reaction mixture was
treated to give the title compound (280 mg) as a white powder.
[0964] mp 103-104.5.degree. C.
[0965] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.15-3.22 (2H, m), 3.89 (2H, q, J=5.0 Hz), 4.13-4.22
(4H, m), 4.74 (1H, dd, J=6.0, 7.5 Hz), 6.62 (1H, t, J=5.0 Hz), 6.84
(2H, d, J=9.0 Hz), 6.87 (2H, d, J=9.0 Hz), 6.94 (1H, t, J=7.5 Hz),
7.19-7.25 (4H, m), 7.35-7.50 (3H, m), 7.57-7.63 (2H, m), 7.65 (2H,
d, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz).
EXAMPLE 76
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropionic
acid (exemplification No. 6-15 compound)
[0966] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropionate
(270 mg), which is the product of Example 75, was reacted with
aqueous sodium hydroxide solution (1N, 2.00 ml) and the reaction
mixture was treated to give the title compound (250 mg) as a white
powder.
[0967] mp 171-173.degree. C.
[0968] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.20 (2H, d,
J=6.5 Hz), 3.82-3.90 (2H, m), 4.15 (2H, t, J=5.0 Hz), 4.71 (1H, t,
J=6.5 Hz), 6.86 (4H, d, J=8.0 Hz), 6.91 (1H, t, J=7.5 Hz),
7.01-7.12 (1H, m), 7.18-7.27 (4H, m), 7.35-7.50 (3H, m), 7.61 (2H,
d, J=8.5 Hz), 7.65 (2H, d, J=8.5 Hz), 7.88 (2H, d, J=8.0 Hz).
EXAMPLE 77
Ethyl
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxyp-
ropionate (ethyl ester of exemplification No. 6-190 compound)
[0969] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (1.63 g), which is
the product of Reference example 4, 4'-fluorobiphenyl-4-carboxylic
acid (1.20 g) and carbonyldiimidazole (1.08 g) and the reaction
mixture was treated to give the title compound (915 mg) as a white
powder.
[0970] mp 99-101.degree. C.
[0971] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.25 (3H, t,
J=7.0 Hz), 3.22-3.26 (2H, m), 3.94 (2H, q, J=5.0 Hz), 4.20 (2H, t,
J=5.0 Hz), 4.22 (2H, q, J=7.0 Hz), 4.79 (1H, dd, J=5.5, 7.5 Hz),
6.67 (1H, t, J=5.0 Hz), 6.86-6.93 (4H, m), 6.96-7.01 (1H, m), 7.19
(2H, t, J=8.5 Hz), 7.28 (2H, d, J=8.5 Hz), 7.59-7.68 (4H, m), 7.89
(2H, d, J=8.5 Hz).
EXAMPLE 78
3-[4-[2-(4'-Fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropion-
ic acid (exemplification No. 6-190 compound)
[0972] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropio-
nate (915 mg), which is the product of Example 77, was reacted with
aqueous sodium hydroxide solution (1N, 5.00 ml) and the reaction
mixture was treated to give the title compound (866 mg) as a white
powder.
[0973] mp 195-196.degree. C.
[0974] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.08-3.17 (2H, m), 3.63 (2H, q, J=5.5 Hz), 4.10 (2H, t,
J=5.5 Hz), 4.83-4.89 (1H, m), 6.83 (2H, d, J=8.5 Hz), 6.88-6.95
(3H, m), 7.23-7.39 (6H, m), 7.73-7.84 (4H, m), 7.95 (2H, d, J=8.0
Hz), 8.75 (1H, t, J=5.5 Hz).
EXAMPLE 79
Ethyl
3-[4-[2-(4'-chlorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxyp-
ropionate (ethyl ester of exemplification No. 6-204 compound)
[0975] A solution of diethyl cyanophosphonate (0.76 ml) in
tetrahydrofuran (10 ml) was added to a solution of ethyl
3-[4-(2-aminoethoxy)phenyl]-2-ph- enoxypropionate (1.50 g),
4'-chlorobiphenyl-4-carboxylic acid (1.17 g) and triethylamine
(0.70 ml) in tetrahydrofuran (20 ml) in an ice bath. The mixture
was stirred for 1 hour in an ice bath and for 4 hours at ambient
temperature. At the end of this time the solvent was distilled off
under reduced pressure. The residue was partitioned between ethyl
acetate and water and the ethyl acetate layer was separated and
washed with saturated aqueous sodium hydrogencarbonate solution and
dried over anhydrous magnesium sulfate and concentrated under
reduced pressure. The residue was purified via chromatography on a
silica gel column using dichloroethane/ethyl acetate=19/1 as the
eluant to give the title compound (0.90 g) as a pale yellow
oil.
[0976] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.12-3.21 (2H, m), 3.79-3.90 (2H, m), 4.05-4.21 (4H, m),
4.69-4.79 (1H, m), 6.68-6.78 (1H, m), 6.80-6.89 (4H, m), 6.90-6.96
(1H, m), 7.16-7.27 (4H, m), 7.41 (2H, d, J=8.5 Hz), 7.51 (2H, d,
J=8.5 Hz), 7.58 (2H, d, J=8.5 Hz), 7.84 (2H, d, J=8.5 Hz).
EXAMPLE 80
3-[4-[2-(4'-Chlorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropion-
ic acid (exemplification No. 6-204 compound)
[0977] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4'-chlorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropio-
nate (900 mg), which is the product of Example 79, was reacted with
aqueous sodium hydroxide solution (1N, 5.00 ml) and the reaction
mixture was treated to give the title compound (638 mg) as a white
powder.
[0978] mp 194.5-197.degree. C.
[0979] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.05-3.15 (2H, m), 3.58-3.67 (2H, m), 4.01-4.12 (2H,
m), 4.80-4.89 (1H, m), 6.78-6.95 (5H, m), 7.18-7.28 (4H, m), 7.55
(2H, d, J=8.5 Hz), 7.71-7.81 (4H, m), 7.96 (2H, d, J=8.0 Hz),
8.71-8.79 (1H, m).
EXAMPLE 81
Ethyl
3-[4-[2-(4'-trifluoromethylbiphenyl-4-carbonylamino)ethoxy]phenyl]-2-
-phenoxypropionate (ethyl ester of exemplification No. 6-191
compound)
[0980] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (1.60 g), which is
the product of Reference example 4,
4'-trifluoromethylbiphenyl-4-carboxylic acid (1.30 g) and
carbonyldiimidazole (0.95 g) and the reaction mixture was treated
to give the title compound (1.10 g) as a pale yellow oil.
[0981] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.25 (3H, t,
J=7.0 Hz), 3.18-3.25 (2H, m), 3.95 (2H, q, J=5.0 Hz), 4.20 (2H, t,
J=5.0 Hz), 4.22 (2H, q, J=7.0 Hz), 4.79 (1H, dd, J=5.5, 7.5 Hz),
6.70 (1H, t, J=5.0 Hz), 6.82-6.98 (5H, m), 7.20-7.32 (4H, m),
7.65-7.76 (6H, m), 7.93 (2H, d, J=8.5 Hz).
EXAMPLE 82
3-[4-[2-(4'-Trifluoromethylbiphenyl-4-carbonylamino)ethoxy]phenyl]-2-pheno-
xypropionic acid (exemplification No. 6-191 compound)
[0982] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4'-trifluoromethylbiphenyl-4-carbonylamino)ethoxy]phenyl]-2-phen-
oxypropionate (1.10 g), which is the product of Example 81, was
reacted with aqueous sodium hydroxide solution (1N, 5.00 ml) and
the reaction mixture was treated to give the title compound (850
mg) as a white powder.
[0983] mp 217-218.5.degree. C.
[0984] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.06-3.16 (2H, m), 3.66 (2H, q, J=5.5 Hz), 4.11 (2H, t,
J=5.5 Hz), 4.85 (1H, dd, J=5.0, 7.5 Hz), 6.80-6.96 (5H, m),
7.20-7.28 (4H, m), 7.85 (4H, d, J=8.5 Hz), 7.94-8.02 (4H, m), 8.80
(1H, t, J=5.5 Hz).
EXAMPLE 83
Sodium
3-[4-[2-(4'-hydroxy-3',5'-dimethylbiphenyl-4-carbonylamino)ethoxy]p-
henyl]-2-phenoxypropionate (exemplification No. 6-205 compound)
[0985] In a similar manner to that described in Example 36,
3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carbonylamino)ethoxy]-
phenyl]-2-phenoxypropionic acid (330 mg), which is the product of
Reference example 24, was reacted with a dioxane solution of
hydrogen chloride (4N, 3.30 ml) and the reaction mixture was
treated to give the title compound (257 mg) as a white powder.
[0986] mp 134-135.degree. C.
[0987] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 2.23 (6H, s), 2.90 (1H, dd, J=9.5, 14.5 Hz), 3.05 (1H,
dd, J=1.5, 14.5 Hz), 3.61 (2H, q, J=5.5 Hz), 4.07 (2H, t, J=5.5
Hz), 4.32 (1H, dd, J=1.5, 9.5 Hz), 6.74 (2H, d, J=7.5 Hz), 6.78
(1H, d, J=7.5 Hz), 6.85 (2H, d, J=8.5 Hz), 7.13 (2H, d, J=7.5 Hz),
7.19 (2H, d, J=8.5 Hz), 7.31 (2H,.s), 7.66 (2H, d, J=8.5 Hz), 7.89
(2H, d, J=8.5 Hz), 8.54 (1H, brs), 8.68 (1H, brt).
EXAMPLE 84
Ethyl
3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]phenyl]-2-phenoxyp-
ropionate (ethyl ester of exemplification No. 6-96 compound)
[0988] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (753 mg), which is
the product of Reference example 4, 6-methoxynicotinic acid (350
mg) and carbonyldiimidazole (445 mg) and the reaction mixture was
treated to give the title compound (355 mg) as a white powder.
[0989] mp 114-116.degree. C.
[0990] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17-3.20 (2H, m), 3.85 (2H, q, J=5.0 Hz), 3.98 (3H, s),
4.12 (2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.73 (1H, dd,
J=6.0, 7.0 Hz), 6.48 (1H, t, J=5.0 Hz), 6.77 (1H, d, J=8.5 Hz),
6.82-6.86 (4H, m), 6.94 (1H, t, J=7.5 Hz), 7.20-7.28 (4H, m), 7.98
(1H, dd, J=2.5, 8.5 Hz), 8.59 (1H, d, J=2.5 Hz).
EXAMPLE 85
3-[4-[2-(2-Methoxypyridine-5-carbonylamino)ethoxy]phenyl]-2-phenoxypropion-
ic acid (exemplification No. 6-96 compound)
[0991] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(2-methoxypyridine-5-carbonylamino)ethoxy]phenyl]-2-phenoxypropio-
nate (330 mg), which is the product of Example 84, was reacted with
aqueous sodium hydroxide solution (1N, 2.50 ml) and the reaction
mixture was treated to give the title compound (260 mg) as
colorless crystals.
[0992] mp 145-146.5.degree. C. 1H-NMR (270 MHz, CDCl.sub.3):
.delta. ppm 3.18-3.23 (2H, m), 3.81 (2H, q, J=5.0 Hz), 3.97 (3H,
s), 4.14 (2H, t, J=5.0 Hz), 4.71 (1H, dd, J=5.5, 7.0 Hz), 6.76 (1H,
d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 6.93
(1H, t, J=8.0 Hz), 7.02-7.11 (1H, m), 7.17-7.27 (4H, m), 8.02 (1H,
dd, J=2.5, 8.5 Hz), 8.60 (1H, d, J=2.5 Hz).
EXAMPLE 86
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropylpheno-
xy)propionate (ethyl ester of exemplification No. 7-15
compound)
[0993] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (723 mg), which is the product of
Reference example 25, biphenyl-4-carboxylic acid (303 mg), diethyl
cyanophosphonate (0.25 ml) and triethylamine (0.47 ml) and the
reaction mixture was treated to give the title compound (630 mg) as
a yellow oil.
[0994] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.21 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.15-3.20 (2H, m), 3.89 (2H, q, J=5.0 Hz), 4.15 (2H, t, J=5.0 Hz),
4.20 (2H, q, J=7.0 Hz), 4.69 (1H, dd, J=5.5, 7.5 Hz), 6.64 (1H, t,
J=5.0 Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.08
(2H, d, J=8.5 Hz), 7.24 (2H, d, J=8.5 Hz), 7.35-7.51 (3H, m),
7.59-7.63 (2H, m), 7.66 (2H, d, J=8.5 Hz), 7.86 (2H, d, J=8.5
Hz).
EXAMPLE 87
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropylphenoxy)pro-
pionic acid (exemplification No. 7-15 compound)
[0995] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropylphenoxy)pr-
opionate (630 mg), which is the product of Example 86, was reacted
with aqueous sodium hydroxide solution (1N, 2.00 ml) and the
reaction mixture was treated to give the title compound (510 mg) as
a white powder.
[0996] mp 172-173.degree. C.
[0997] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz), 3.21 (2H, d, J=6.0 Hz),
3.86 (2H, q, J=5.0 Hz), 4.12 (2H, t, J=5.0 Hz), 4.78 (1H, t, J=6.0
Hz), 6.68 (1H, t, J=5.0 Hz), 6.79 (2H, d, J=8.5 Hz), 6.85 (2H, d,
J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.23 (2H, d, J=8.5 Hz),
7.35-7.49 (3H, m), 7.57-7.62 (2H, m), 7.65 (2H, d, J=8.5 Hz), 7.85
(2H, d, J=8.5 Hz).
EXAMPLE 88
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)e-
thoxy]phenyl]propionate (ethyl ester of exemplification No. 7-179
compound)
[0998] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (723 mg), which is the product of
Reference example 25, 4'-methoxybiphenyl-4-carboxylic acid (350
mg), diethyl cyanophosphonate (0.25 ml) and triethylamine (0.47 ml)
and the reaction mixture was treated to give the title compound
(600 mg) as a white powder.
[0999] mp 116-117.degree. C.
[1000] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.20 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.15-3.21 (2H, m), 3.86 (3H, s), 3.86-3.91 (2H, m), 4.14 (2H, t,
J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.69 (1H, dd, J=6.0, 7.0 Hz),
6.62 (1H, t, J=5.0 Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5
Hz), 6.99 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.23 (2H, d,
J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz), 7.61 (2H, d, J=8.0 Hz), 7.83
(2H, d, J=8.0 Hz).
EXAMPLE 89
2-(4-Isopropylphenoxy)-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy]-
phenyl]propionic acid (exemplification No. 7-179 compound)
[1001] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy-
]phenyl]propionate (580 mg), which is the product of Example 88,
was reacted with aqueous sodium hydroxide solution (1N, 2.00 ml)
and the reaction mixture was treated to give the title compound
(450 mg) as a white powder.
[1002] mp 159-160.degree. C.
[1003] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.18 (6H, d,
J=6.5 Hz), 2.77-2.80 (1H, m), 3.18-3.27 (2H, m), 3.80-3.90 (5H, m),
4.10-4.18 (2H, m), 4.76-4.82 (1H, m), 6.67-6.70 (1H, m), 6.78 (2H,
d, J=8.0 Hz), 6.84 (2H, d, J=8.0 Hz), 6.98 (2H, d, J=8.0 Hz), 7.09
(2H, d, J=8.0 Hz), 7.22 (2H, d, J=8.0 Hz), 7.54 (2H, d, J=8.0 Hz),
7.59 (2H, d, J=8.0 Hz), 7.81 (2H, d, J=8.0 Hz).
EXAMPLE 90
Ethyl
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopr-
opylphenoxy)-propionate (ethyl ester of exemplification No. 7-190
compound)
[1004] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (723 mg), which is the product of
Reference example 25, 4'-fluorobiphenyl-4-carboxylic acid (331 mg),
diethyl cyanophosphonate (0.25 ml) and triethylamine (0.47 ml) and
the reaction mixture was treated to give the title compound (460
mg) as a colorless oil.
[1005] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.20 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.12-3.18 (2H, m), 3.88 (2H, q, J=5.0 Hz), 4.13 (2H, t, J=5.0 Hz),
4.18 (2H, q, J=7.0 Hz), 4.69 (1H, dd, J=6.0, 7.0 Hz), 6.63 (1H, t,
J=5.0 Hz), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz),
7.00-7.29 (6H, m), 7.53-7.60 (2H, m), 7.60 (2H, d, J=8.5 Hz), 7.84
(2H, d, J=8.5 Hz).
EXAMPLE 91
3-[4-[2-(4'-Fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropylph-
enoxy)propionic acid (exemplification No. 7-190 compound)
[1006] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4'-fluorobiphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-isopropylp-
henoxy)propionate (450 mg), which is the product of Example 90, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (380
mg) as a white powder.
[1007] mp 192-193.degree. C.
[1008] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.17 (6H, d,
J=7.0 Hz), 2.84 (1H, septet, J=7.0 Hz), 3.18 (2H, d, J=6.0 Hz),
3.84 (2H, q, J=5.0 Hz), 4.16 (2H, t, J=5.0 Hz), 4.66 (1H, t, J=6.0
Hz), 6.77 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.07 (2H, d,
J=8.5 Hz), 7.10-7.19 (2H, m), 7.22-7.33 (3H, m), 7.55-7.62 (4H, m),
7.90 (2H, d, J=8.5 Hz).
EXAMPLE 92
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)e-
thoxy]phenyl]propionate (ethyl ester of exemplification No. 7-212
compound)
[1009] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (723 mg),which is the product of
Reference example 25, 3'-methoxybiphenyl-4-carboxylic acid (350
mg), diethyl cyanophosphonate (0.25 ml) and triethylamine (0.47 ml)
and the reaction mixture was treated to give the title compound
(700 mg) as a pale yellow oil.
[1010] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (6H, d,
J=7.0 Hz), 1.24 (3H, t, J=7.0 Hz), 2.85 (1H, septet, J=7.0 Hz),
3.18-3.25 (2H, m), 3.91 (3H, s), 3.92-3.99 (2H, m), 4.12-4.28 (4H,
m), 4.73 (1H, dd, J=6.0, 7.0 Hz), 6.62-6.70 (1H, m), 6.79 (2H, d,
J=8.5 Hz), 6.90 (2H, d, J=8.5 Hz), 6.97 (1H, dd, J=2.5, 8.0 Hz),
7.12 (2H, d, J=8.5 Hz), 7.17 (1H, d, J=2.5 Hz), 7.20-7.30 (3H, m),
7.41 (1H, t, J=8.0 Hz), 7.69 (2H, d, J=8.5 Hz), 7.88 (2H, d, J=8.5
Hz).
EXAMPLE 93
2-(4-Isopropylphenoxy)-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy]-
phenyl]propionic acid (exemplification No. 7-212 compound)
[1011] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(3'-methoxybiphenyl-4-carbonylamino)ethoxy-
]phenyl]propionate (700 mg), which is the product of Example 92,
was reacted with aqueous sodium hydroxide solution (1N, 3.00 ml)
and the reaction mixture was treated to give the title compound
(310 mg) as a white powder.
[1012] mp 138-139.degree. C.
[1013] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.24 (6H, d,
J=7.0 Hz), 2.89 (1H, septet, J=7.0 Hz), 3.27 (2H, d, J=6.0 Hz),
3.93 (3H, s), 3.84-3.96 (2H, m), 4.18 (2H, t, J=5.0 Hz), 4.85 (1H,
t, J=6.0 Hz), 6.74 (1H, t, J=5.0 Hz), 6.85 (2H, d, J=8.5 Hz), 6.91
(2H, d, J=8.5 Hz), 6.99 (1H, dd, J=2.5, 8.0 Hz), 7.16 (2H, d, J=8.5
Hz), 7.20-7.27 (2H, m), 7.29 (2H, d, J=8.5 Hz), 7.44 (1H, t, J=8.0
Hz), 7.70 (2H, d, J=8.0 Hz), 7.90 (2H, d, J=8.0 Hz).
EXAMPLE 94
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)e-
thoxy]phenyl]propionate (ethyl ester of exemplification No. 7-219
compound)
[1014] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (723 mg), which is the product of
Reference example 25, 2'-methoxybiphenyl-4-carboxylic acid (350
mg), diethyl cyanophosphonate (0.25 ml) and triethylamine (0.47 ml)
and the reaction mixture was treated to give the title compound
(710 mg) as a colorless oil.
[1015] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.20 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.15-3.20 (2H, m), 3.81 (3H, s), 3.88 (2H, q, J=5.0 Hz), 4.14 (2H,
t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.66-4.72 (1H, m), 6.62 (1H,
t, J=5.0 Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz),
6.98-7.10 (4H, m), 7.21-7.38 (4H, m), 7.60 (2H, d, J=8.0 Hz), 7.81
(2H, d, J=8.0 Hz).
EXAMPLE 95
Sodium
2-(4-isopropylphenoxy)-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)-
ethoxy]phenyl]propionate (exemplification No. 7-219 compound)
[1016] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(2'-methoxybiphenyl-4-carbonylamino)ethoxy-
]phenyl]propionate (700 mg), which is the product of Example 94,
was reacted with aqueous sodium hydroxide solution (1N, 3.60 ml)
and the reaction mixture was treated to give the title compound
(528 mg) as a white powder.
[1017] mp 205-208.degree. C.
[1018] .sup.1H-NMR of free acid (270 MHz, CD.sub.3Cl): .delta. ppm
1.18 (6H, d, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz), 3.21 (2H, d,
J=6.5 Hz), 3.80 (3H, s), 3.86 (2H, q, J=5.0 Hz), 4.12 (2H, t, J=5.0
Hz), 4.78 (1H, t, J=6.5 Hz), 6.66 (1H, t, J=5.0 Hz), 6.78 (2H, d,
J=8.5 Hz), 6.84 (2H, d, J=8.5 Hz), 6.97-7.07 (2H, m), 7.10 (2H, d,
J=8.5 Hz), 7.22 (2H, d, J=8.5 Hz), 7.28-7.37 (2H, m), 7.59 (2H, d,
J=8.5 Hz), 7.80 (2H, d, J=8.5 Hz).
EXAMPLE 96
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(2-phenylpyridine-5-carbonylamino)eth-
oxy]phenyl]propionate (ethyl ester of exemplification No. 7-95
compound)
[1019] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy- )propionate (743
mg), which is the product of Reference example 5, 6-phenylnicotinic
acid (438 mg) and carbonyldiimidazole (357 mg) and the reaction
mixture was treated to give the title compound (196 mg) as
colorless crystals.
[1020] mp 113-114.degree. C.
[1021] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.10-1.23
(9H, m), 2.72-2.88 (1H, m), 3.12-3.19 (2H, m), 3.82-3.93 (2H, m),
4.10-4.23 (4H, m), 4.69 (1H, dd, J=5.5, 7.5 Hz), 6.61-6.69 (1H, m),
6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz), 7.24 (2H, d, J=8.5 Hz), 7.41-7.53 (3H, m), 7.81 (1H, d, J=8.5
Hz), 8.00-8.08 (2H, m), 8.12-8.20 (1H,m ), 9.01-9.39 (1H, m).
EXAMPLE 97
2-(4-Isopropylphenoxy)-3-[4-[2-(2-phenylpyridine-5-carbonylamino)ethoxy]ph-
enyl]propionic acid (exemplification No. 7-95 compound)
[1022] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(2-phenylpyridine-5-carbonylamino)ethoxy]p-
henyl]propionate (169 mg), which is the product of Example 96, was
reacted with aqueous sodium hydroxide solution (1N, 0.60 ml) and
the reaction mixture was treated to give the title compound (126
mg) as colorless crystals.
[1023] mp 174-176.degree. C.
[1024] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 2.79-2.90 (1H, m), 3.27 (2H, d, J=5.5 Hz), 3.71-3.88
(1H, m), 3.88-4.01 (1H, m), 4.28-4.40 (2H, m), 4.94 (1H, t, J=5.5
Hz), 6.50-6.59 (1H, m), 6.84 (2H, d, J=8.5 Hz), 6.95 (2H, d, J=8.5
Hz), 7.11 (2H, d, J=8.5 Hz), 7.30 (2H, d, J=8.5 Hz), 7.42-7.49 (3H,
m), 7.75-7.81 (1H, m), 7.85-7.92 (2H,m), 8.25-8.31 (2H, m).
EXAMPLE 98
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(2-(4-methoxyphenyl)-pyridine-5-carbo-
nylamino)ethoxy]phenyl]propionate (ethyl ester of exemplification
No. 7-233 compound)
[1025] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy- )propionate (743
mg), which is the product of Reference example 5,
6-(4-methoxyphenyl)nicotinic acid (504 mg) which is the product of
Rreference example 26, and carbonyldiimidazole (357 mg) and the
reaction mixture was treated to give the title compound (182 mg) as
colorless crystals.
[1026] mp 100-101.degree. C.
[1027] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13-1.23
(9H, m), 2.74-2.89 (1H, m), 3.12-3.19 (2H, m), 3.88 (3H, s),
3.86-3.93 (2H, m), 4.11-4.23 (4H, m), 4.69 (1H, dd, J=5.5, 7.5 Hz),
6.59-6.65 (1H, m), 6.75 (2H, d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz),
7.01 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.24 (2H, d, J=8.5
Hz), 7.74 (1H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz), 8.13 (1H, dd,
J=2.0, 8.5 Hz), 9.01 (1H, d, J=2.0 Hz).
EXAMPLE 99
2-(4-Isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-carbonylamin-
o]ethoxy]phenyl]propionic acid (exemplification No. 7-233
compound)
[1028] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-carbonylami-
no]ethoxy]phenyl]propionate (170 mg), which is the product of
Example 98, was reacted with aqueous sodium hydroxide solution (1N,
0.58 ml) and the reaction mixture was treated to give the title
compound (153 mg) as colorless crystals.
[1029] mp 166-167.degree. C.
[1030] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 2.78-2.90 (1H, m), 3.27 (2H, d, J=5.5 Hz), 3.86 (3H, s),
3.70-4.01 (2H, m), 4.29-4.39 (2H, m), 4.95 (1H, t, J=5.5 Hz),
6.43-6.51 (1H, m), 6.84 (2H, d, J=8.5 Hz), 6.90-7.00 (4H, m), 7.12
(2H, d, J=8.5 Hz), 7.30 (2H, d, J=8.5 Hz), 7.73 (1H, d, J=8.5 Hz),
7.80-7.88 (2H, m), 8.19 (1H, d, J=2.5 Hz), 8.27 (1H, dd, J=2.5, 8.5
Hz).
EXAMPLE 100
Ethyl
3-[4-[2-[2-(4-fluorophenyl)pyridine-5-carbonylamino]ethoxy]phenyl]-2-
-(4-isopropylphenoxy)propionate (ethyl ester of exemplification No.
7-231 compound)
[1031] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)propionate (718 mg), which is the product of
Reference example 25, 6-(4-fluorophenyl)nicotinic acid (330 mg),
which is the product of Reference example 27, diethyl
cyanophosphonate (0.25 ml) and triethylamine (0.47 ml) and the
reaction mixture was treated to give the title compound (560 mg) as
a white powder.
[1032] mp 117-118.degree. C.
[1033] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.21 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.15-3.20 (2H, m), 3.90 (2H, q, J=5.0 Hz), 4.13-422 (4H, m), 4.69
(1H, dd, J=5.5, 7.0 Hz), 6.66 (1H, t, J=5.0 Hz), 6.75 (2H, d, J=8.5
Hz), 6.86 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.14-7.25 (4H,
m), 7.76 (1H, d, J=8.5 Hz), 8.00-8.07 (2H, m), 8.16 (1H, dd, J=2.0,
8.5 Hz), 9.03 (1H, d, J=2.0 Hz).
EXAMPLE 101
3-[4-[2-[2-(4-Fluorophenyl)pyridine-5-carbonylamino]ethoxy]phenyl]-2-(4-is-
opropylphenoxy)propionic acid (exemplification No. 7-231
compound)
[1034] In a similar manner to that described in Example 2, ethyl
3-[4-[2-[2-(4-fluorophenyl)pyridine-5-carbonylamino]ethoxy]-phenyl]-2-(4--
isopropylphenoxy)propionate (540 mg), which is the product of
Example 100, was reacted with aqueous sodium hydroxide solution
(1N, 3.00 ml) and the reaction mixture was treated to give the
title compound (495 mg) as a white powder.
[1035] mp 199-200.degree. C.
[1036] .sup.1H-NMR (270 MHz, CD.sub.3Cl): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 2.84 (1H, septet, J=7.0 Hz), 3.20-3.23 (2H, m), 3.86
(2H, q, J=5.5 Hz), 4.21 (2H, t, J=5.5 Hz), 4.70 (1H, dd, J=5.5, 7.0
Hz), 6.80 (2H, d, J=8.5 Hz), 6.89 (2H, d, J=8.5 Hz), 7.10 (2H, d,
J=8.5 Hz), 7.13-7.30 (4H, m), 7.79 (1H, d, J=8.5 Hz), 7.92 (1H, t,
J=5.5 Hz), 8.03-8.09 (2H, m), 8.25 (1H, dd, J=2.0, 8.5 Hz), 9.12
(1H, d, J=2.0 Hz).
EXAMPLE 102
Ethyl
3-[4-[2-[2-(2,2,3,3,-tetrafluoropropoxy)pyridine-5-carbonylamino]eth-
oxy]-phenyl]-2-(4-isopropylphenoxy)propionate (ethyl ester of
exemplification No. 7-236 compound)
[1037] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy- )propionate (500
mg), which is the product of Reference example 5,
6-(2,2,3,3-tetrafluoropropoxy)nicotinic acid (375 mg), which is the
product of Reference example 28, and carbonyldiimidazole (240 mg)
and the reaction mixture was treated to give the title compound
(137 mg) as a colorless oil.
[1038] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.11-1.28
(9H, m), 2.82 (1H, septet, J=7.0 Hz), 3.10-3.20 (2H, m), 3.83 (2H,
q, J=7.0 Hz), 4.08-4.25 (4H, m), 4.68-4.87 (3H, m), 5.99 (1H, tt,
J=4.5, 53 Hz), 6.63-6.89 (6H, m), 7.08 (2H, d, J=8.5 Hz), 7.22 (2H,
d, J=8.5 Hz), 8.05 (1H, dd, J=2.5, 8.5 Hz), 8.58 (1H, d, J=2.5
Hz).
EXAMPLE 103
Sodium
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino]eth-
oxy]-phenyl]-2-(4-isopropylphenoxy)propionate (exemplification No.
7-236 compound)
[1039] In a similar manner to that described in Example 2, ethyl
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino]ethoxy]ph-
enyl]-2-(4-isopropylphenoxy)propionate (73 mg), which is the
product of Example 102, was reacted with aqueous sodium-hydroxide
solution (1N, 0.13 ml) and the reaction mixture was treated to give
the title compound (51 mg) as colorless crystals.
[1040] mp 204-207.degree. C.
[1041] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm
1.11-1.21 (6H, m), 2.77 (1H, septet, J=7.0 Hz), 2.99-3.17 (2H, m),
3.73 (2H, t, J=5.5 Hz), 4.12 (2H, t, J=5.5 Hz), 4.78-4.90 (3H, m),
6.30 (1H, tt, J=5.0, 53 Hz), 6.74 (2H, d, J=8.5 Hz), 6.85 (2H, d,
J=8.5 Hz), 6.93 (1H, d, J=8.5 Hz), 7.01 (2H, d, J=8.5 Hz), 7.25
(2H, d, J=8.5 Hz), 8.13 (1H, dd, J=2.5, 8.5 Hz), 8.64 (1H, d, J=2.5
Hz).
EXAMPLE 104
(S)-2-(4-Isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]-propionic acid (an optically active compound of
exemplification No. 7-35 compound)
[1042] A tetrahydrofuran solution of tetrabutylammonium fluoride
(1M, 2.25 ml) was added to a solution of 2-trimethylsilylethyl
(S)-2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]ph-
enyl]propionate (562 mg), which is the product of Reference example
29, in tetrahydrofuran (4.0 ml) at ambient temperature. After the
mixture was stirred for 1 hour, the reaction mixture was
concentrated under reduced pressure. The residue was partitioned
between ethyl acetate and water. The ethyl acetate layer was washed
with aqueous hydrochloric acid solution (0.5 N) and saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and then concentrated under reduced pressure. The residue
was purified via chromatography on a thin layer plate using
dichloromethane/methanol=5/1 as the eluant. The product was
crystallized from diisopropyl ether to give the title compound (278
mg) as colorless crystals.
[1043] mp 100-101.degree. C.
[1044] [.alpha.].sub.D.sup.25+13.9.degree. (c=0.9, chloroform)
[1045] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 1.11 (6H, d,
J=7.0 Hz), 2.74 (1H, septet, J=7.0 Hz), 3.02-3.16 (2H, m),
3.73-3.82 (2H, m), 3.98-4.07 (2H, m), 4.63-4.74 (1H, m), 6.69-6.80
(4H, m), 6.95-7.01 (3H, m), 7.11 (2H, d, J=8.0 Hz), 7.25-7.31(1H,
m), 7.68 (1H, d, J=8.0 Hz), 7.72-7.85 (3H, m), 7.93 (2H, d, J=8.0
Hz), 8.69 (1H, d, J=4.5 Hz).
EXAMPLE 105
(R)-2-(4-Isopropylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylmino)ethoxy]phen-
yl]propionic acid (an optical active compound of exemplification
No. 7-35 compound)
[1046] In a similar manner to that described in Example 104, a
reaction was carried out using 2-trimethylsilylethyl
(R)-2-(4-isopropylphenoxy)-3--
[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate (270
mg), which is the product of Reference example 30 and
tetrabutylammonium fluoride in tetrahydrofuran (1M, 1.08 ml) and
the reaction mixture was treated to give the title compound (117
mg) as colorless crystals. mp 95-96.degree. C.
[1047] [.alpha.].sub.D.sup.25-10.5.degree. (c=1.5, chloroform)
[1048] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 1.11 (6H, d,
J=7.0 Hz), 2.73 (1H, septet, J=7.0 Hz), 3.02-3.16 (2H, m),
3.73-3.82 (2H, m), 3.98-4.07 (2H, m), 4.63-4.74 (1H, m), 6.69-6.80
(4H, m), 6.95-7.02 (3H, m), 7.12 (2H, d, J=8.0 Hz), 7.25-7.31 (1H,
m), 7.65 (1H, d, J=8.0 Hz), 7.72-7.83 (3H, m), 7.88 (2H, d, J=8.0
Hz), 8.70 (1H, d, J=4.5 Hz).
EXAMPLE 106
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-trifluoromethylpyridine-6-yl)be-
nzoylamino]ethoxy]phenyl]propionate (ethyl ester of exemplification
No. 7-227 compound)
[1049] One drop of N,N-dimethylformamide and thionyl chloride (0.75
ml) were added to a solution of
3-trifluoromethylpyridine-6-ylbenzoic acid (546 mg) in toluene
(28.0 ml) at ambient temperature. After the mixture was stirred for
4 hours at 85.degree. C., the solvent was distilled off and the
thionyl chloride was azeotropically evaporated with toluene to
dryness under reduced pressure. Triethylamine (1.23 ml) was added
to a solution of the residue obtained above and ethyl
3-[4-(2-aminoethoxy)phen- yl]-2-(4-isopropylphenoxy)propionate (201
mg), which is the product of Reference example 5, in
dichloromethane (10 ml) in an ice bath. After the mixture was
stirred for 30 minutes, the reaction mixture was concentrated. The
residue was partitioned between ethyl acetate and water. The ethyl
acetate layer was separated and washed with saturated aqueous
sodium chloride and dried over anhydrous magnesium sulfate and then
evaporated under reduced pressure. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=3/2-1/1 as the eluant to give the title compound (570 mg)
as a mass of yellow foam.
[1050] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.21 (3H, t, J=7.0 Hz), 2.81 (1H, septet, J=7.0 Hz),
3.17 (2H, d, J=6.5 Hz), 3.90 (2H, q, J=5.0 Hz), 4.14 (2H, t, J=5.0
Hz), 4.18 (2H, t, J=7.0 Hz), 4.70 (1H, t, J=6.5 Hz), 6.67 (1H,
brt), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.07 (2H, d,
J=8.5 Hz), 7.24 (2H, d, J=8.5 Hz), 7.88 (1H, d, J=8.5 Hz), 7.91
(2H, d, J=8.5 Hz), 8.01 (1H, d, J=8.5 Hz), 8.12 (2H, d, J=8.5 Hz),
8.99 (1H, s).
EXAMPLE 107
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-trifluoromethylpyridine-6-yl)benzoyla-
mino]-ethoxy]phenyl]propionic acid (exemplification No. 7-227
compound)
[1051] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-trifluoromethylpyridine-6-yl)benzoyl-
amino]ethoxy]phenyl]propionate (500 mg), which is the product of
Example 106, was reacted with aqueous sodium hydroxide solution
(1N, 1.60 ml) and the reaction mixture was treated to give the
title compound (383 mg) as a white powder.
[1052] mp 212-214.degree. C.
[1053] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 1.13 (6H, d, J=7.0 Hz), 2.78 (1H, septet, J=7.0 Hz),
3.07 (1H, d, J=7.0 Hz), 3.09 (1H, d, J=5.0 Hz), 3.64 (2H, q, J=5.5
Hz), 4.11 (2H, t, J=5.5 Hz), 4.77 (1H, dd, J=5.0, 7.0 Hz), 6.74
(2H, d, J=8.5 Hz), 6.90 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz),
7.23 (2H, d, J=8.5 Hz), 8.02 (2H, d, J=8.5 Hz), 8.27 (2H, d, J=8.5
Hz), 8.30-8.36 (2H, m), 8.84 (1H, brt), 9.08 (1H, s).
EXAMPLE 108
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-nitropyridine-6-yl)benzoylamino-
]ethoxy]phenyl]propionic acid (ethyl ester of exemplification No.
7-228 compound)
[1054] In a similar manner to that described in Example 79, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy- )propionate (290
mg), which is the product of Reference example 5,
3-nitropyridine-6-ylbenzoic acid (277 mg), which is the product of
Reference example 32, diethyl cyanophosphonate (0.18 ml) and
triethylamine (0.29 ml) and the reaction mixture was treated to
give the title compound (379 mg) as a syrup.
[1055] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.21 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.17 (1H, d, J=5.0 Hz), 3.18 (1H, d, J=7.5 Hz), 3.90 (2H, q, J=5.0
Hz), 4.06-4.39 (4H, m), 4.69 (1H, dd, J=5.0, 7.5 Hz), 6.68 (1H,
brt), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J-8.5 Hz), 7.13 (2H, d,
J=8.5 Hz), 7.24 (2H, d, J=8.5 Hz), 7.93 (2H, d, J=8.5 Hz), 7.95
(1H, d, J=8.5 Hz), 8.17 (2H, d, J=8.5 Hz), 8.56 (1H, dd, J=2.0, 8.5
Hz), 9.51 (1H, d, J=2.0 Hz).
EXAMPLE 109
2-(4-Isopropylphenoxy)-3-[4-[2-[4-(3-nitropyridine-6-yl)benzoylamino]ethox-
y]phenyl]propionic acid (exemplification No. 7-228 compound)
[1056] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-nitropyridine-6-yl)benzoylamino]etho-
xy]phenyl]propionate (397 mg), which is the product of Example 108,
was reacted with aqueous sodium hydroxide solution (1N, 1.30 ml)
and the reaction mixture was treated to give the title compound
(216 mg) as a white powder.
[1057] mp 198-199.degree. C.
[1058] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 1.13 (6H, d, J=7.0 Hz), 2.79 (1H, septet, J=7.0 Hz),
3.07 (1H, d, J=7.5 Hz), 3.09 (1H, d, J=5.5 Hz), 3.65 (2H, q, J=5.5
Hz), 4.11 (2H, t, J=5.5 Hz), 4.78 (1H, dd, J=5.5, 7.5 Hz), 6.74
(2H, d, J=8.5 Hz), 6.90 (2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz),
7.23 (2H, d, J=8.5 Hz), 8.04 (2H, d, J=8.5 Hz), 8.31 (2H, d, J=8.5
Hz), 8.36 (1H, d, J=8.5 Hz), 8.70 (1H, dd, J=2.0, 8.5 Hz), 8.86
(1H, brt), 9.47 (1H, d, J=2.0 Hz).
EXAMPLE 110
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-methoxypyridine-6-yl)benzoylami-
no]ethoxy]phenyl]propionate (ethyl ester of exemplification No.
7-222 compound)
[1059] In a similar manner to that described in Example 106, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphe- noxy)propionate (301
mg), which is the product of Reference example 5,
3-methoxypyridine-6-ylbenzoic acid (195 mg) which is the product of
Reference example 33, thionyl cloride (0.31 ml) and triethylamine
(0.36 ml) and the reaction mixture was treated to give the title
compound (199 mg) as a white powder.
[1060] mp 118-119.degree. C.
[1061] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.16 (1H, d, J=5.0 Hz), 3.18 (1H, d, J=7.5 Hz), 3.89 (2H, q, J=5.0
Hz), 3.92 (3H, s), 4.15 (2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz),
4.69 (1H, dd, J=5.0, 7.5 Hz), 6.63 (1H, brt), 6.76 (2H, d, J=8.5
Hz), 6.86 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.23 (2H, d,
J=8.5 Hz), 7.28 (1H, dd, J=3.0, 8.5 Hz), 7.71 (1H, d, J=8.5 Hz),
7.86 (2H, d, J=8.5 Hz), 8.01 (2H, d, J=8.5 Hz), 8.41 (1H, d, J=3.0
Hz).
EXAMPLE 111
2-(4-Isopropylphenoxy)-3-[4-[2-[4-(3-methoxypyridine-6-yl)-benzoylamino]et-
hoxy]phenyl]propionic acid (exemplification No. 7-222 compound)
[1062] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[4-(3-methoxypyridine-6-yl)benzoylamino]et-
hoxy]phenyl]propionate (210 mg), which is the product of Example
10, was reacted with aqueous sodium hydroxide solution (1N, 0.72
ml) and the reaction mixture was treated to give the title compound
(185 mg) as a white powder.
[1063] mp 145-146.degree. C.
[1064] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 2.83 (1H, septet, J=7.0 Hz), 3.22 (2H, d, J=6.0 Hz),
3.88 (2H, q, J=5.0 Hz), 3.91 (3H, s), 4.20 (2H, t, J=5.0 Hz), 4.82
(1H, t, J=6.0 Hz), 6.65 (1H, brt), 6.83 (2H, d, J=8.5 Hz), 6.86
(2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz),
7.32 (1H, dd, J=3.0, 9.0 Hz), 7.67 (1H, d, J=9.0 Hz), 7.75 (2H, d,
J=8.5 Hz), 7.88 (2H, d, J=8.5 Hz), 8.41 (1H, d, J=3.0 Hz).
EXAMPLE 112
Ethyl
3-[4-[2-[4-(3-dimethylaminopyridine-6-yl)benzoylamino]ethoxy]phenyl]-
-2-(4-isopropylphenoxy)propionate (ethyl ester of exemplification
No. 7-225 compound)
[1065] In a similar manner to that described in Example 106, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphe- noxy)propionate (370
mg), which is the product of Reference example 5,
3-dimethylaminopyridine-6-ylbenzoic acid (221 mg) which is the
product of Reference example 34, thionyl cloride (0.34 ml) and
triethylamine (0.51ml) and the reaction mixture was treated to give
the title compound (456 mg) as a mass of foam.
[1066] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (6H, d,
J=7.0 Hz), 1.20 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz),
3.04 (6H, s), 3.16(1H, d, J=5.0Hz), 3.17(1H, d, J=7.5Hz), 3.88 (2H,
q, J=5.0 Hz), 4.14 (2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.69
(1H, dd, J=5.0, 7.5 Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5
Hz), 7.06 (1H, dd, J=2.5, 9.0 Hz), 7.08 (2H, d, J=8.5 Hz), 7.23
(2H, d, J=8.5 Hz), 7.45 (1H, brt), 7.64 (1H, d, J=9.0 Hz), 7.83
(2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz), 8.23 (1H, d, J=2.5
Hz).
EXAMPLE 113
3-[4-[2-[4-(3-Dimethylaminopyridine-6-yl)benzoylamino]ethoxy]-phenyl]-2-(4-
-isopropylphenoxy)propionic acid (exemplification No. 7-225
compound)
[1067] In a similar manner to that described in Example 2, ethyl
3-[4-[2-[4-(3-dimethylaminopyridine-6-yl)benzoylamino]ethoxy]-phenyl]-2-(-
4-isopropylphenoxy)propionate (429 mg), which is the product of
Example 112, was reacted with aqueous sodium hydroxide solution
(1N, 1.44 ml) and the reaction mixture was treated to give the
title compound (219 mg) as a white powder.
[1068] mp 150-151.degree. C.
[1069] .sup.1H-NMR (270 MHz, CDCl.sub.3/deuterated methanol=1/5):
.delta. ppm 1.15 (6H, d, J=7.0 Hz), 2.77 (1H, septet, J=7.0 Hz),
3.04 (6H, s), 3.10 (1H, dd, J=8.5, 14.5 Hz), 3.15 (1H, dd, J=4.5,
14.5 Hz), 3.76 (2H, t, J=5.5 Hz), 4.14 (2H, t, J=5.5 Hz), 4.58 (1H,
dd, J=4.5, 8.5 Hz), 6.74 (2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz),
7.02 (2H, d, J=8.5 Hz), 7.22 (1H, dd, J=3.0, 9.0 Hz), 7.23 (2H, d,
J=8.5 Hz), 7.72 (1H, d, J=9.0 Hz), 7.85-7.95 (4H, m), 8.11 (1H, d,
J=3.0 Hz).
EXAMPLE 114
Ethyl
2-(4-methylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionate (ethyl ester of exemplification No. 14-11
compound)
[1070] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
methylphenoxy)propionate (798 mg), which is the product of
Reference example 35, 4-pyridine-2-ylbenzoic acid (365 mg), diethyl
cyanophosphonate (0.28 ml) and triethylamine (0.46 ml) and the
reaction mixture was treated to give the title compound (680 mg) as
a colorless oil.
[1071] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.23 (3H, t,
J=7.0 Hz), 2.28 (3H, s), 3.14-3.22 (2H, m), 3.88-3.96 (2H, m),
4.11-4.27 (4H, m), 4.73 (1H, t, J=6.0 Hz), 6.62-6.71 (1H, m), 6.76
(2H, d, J=8.5 Hz), 6.90 (2H, d, J=8.5 Hz), 7.05 (2H, d, J=8.5 Hz),
7.22-7.33 (3H, m), 7.78-7.83 (2H, m), 7.92 (2H, d, J=8.5 Hz), 8.11
(2H, d, J=8.5 Hz), 8.71-8.78 (1H, m).
EXAMPLE 115
2-(4-Methylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionic acid (exemplification No. 14-11 compound)
[1072] In a similar manner to that described in Example 2, ethyl
2-(4-methylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionate (680 mg), which is the product of Example 114, was reacted
with aqueous sodium hydroxide solution (1N, 2.60 ml) and the
reaction mixture was treated to give the title compound (570 mg) as
a white powder.
[1073] mp 129-131.degree. C.
[1074] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.25 (3H, s),
3.21 (2H, d, J=6.0 Hz), 3.81-3.90 (2H, m), 4.15-4.21 (2H, m), 4.80
(1H, t, J=6.0 Hz), 6.68-6.75 (1H, m), 6.79 (2H, d, J=8.5 Hz), 6.85
(2H, d, J=8.5 Hz), 7.03 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz),
7.29-7.36 (1H, m), 7.70-7.88 (4H, m), 7.92 (2H, d, J=8.5 Hz),
8.69-8.73 (1H, m).
EXAMPLE 116
Ethyl
2-(4-t-butylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate (ethyl ester of exemplification No. 138-8
compound)
[1075] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
t-butylphenoxy)propionate (530 mg), which is the product of
Reference example 36, 4-pyridine-2-ylbenzoic acid (227 mg), diethyl
cyanophosphonate (0.18 ml) and triethylamine (0.33 ml) and the
reaction mixture was treated to give the title compound (370 mg) as
a mass of foam.
[1076] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 1.25 (9H, s), 3.15-3.20 (2H, m), 3.89 (2H, q, J=5.0 Hz),
4.10-422 (4H, m), 4.69 (1H, dd, J=5.5, 7.5 Hz), 6.66 (1H, t, J=5.0
Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 7.23-7.30 (5H,
m), 7.74-7.80 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5
Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 117
2-(4-t-Butylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionic acid (exemplification No. 138-8 compound)
[1077] In a similar manner to that described in Example 2, ethyl
2-(4-t-butylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]p-
ropionate (360 mg), which is the product of Example 116, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (315
mg) as a white powder.
[1078] mp 94-96.degree. C.
[1079] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.24 (9H, s),
3.20 (2H, d, J=6.0 Hz), 3.80-3.90 (2H, m), 4.13-420 (2H, m), 4.79
(1H, t, J=6.0 Hz), 6.76 (1H, t, J=5.0 Hz), 6.82 (2H, d, J=8.0 Hz),
6.85 (2H, d, J=8.0 Hz), 7.22 (2H, d, J=8.0 Hz), 7.25 (2H, d, J=8.0
Hz), 7.28-7.35 (1H, m), 7.70-7.90 (4H, m), 7.91 (2H, d, J=8.5 Hz),
8.73 (1H, d, J=4.5 Hz).
EXAMPLE 118
Ethyl
2-(4-fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionate (ethyl ester of exemplification No. 138-56
compound)
[1080] In a similar manner to that described in Example 65, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-fluorophenoxy)pr- opionate (2.10
g), which is the product of Reference example 37,
4-pyridine-2-ylbenzoylchloride hydrochloride (1.90 g) and
triethylamine (2.20 ml) and the reaction mixture was treated to
give the title compound (2.50 g) as a white powder.
[1081] mp 116-118.degree. C
[1082] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 3.80-3.91 (2H, m), 4.08-4.21
(4H, m), 4.66 (1H, t, J=6.5 Hz), 6.62-6.70 (1H, m), 6.70-6.80 (2H,
m), 6.80-6.92 (4H, m), 7.20-7.30 (3H, m), 7.71-7.80 (2H, m), 7.88
(2H, d, J=8.5 Hz), 8.07 (2H, d, J-8.5 Hz), 8.71 (1H, d, J=5.0
Hz).
EXAMPLE 119
2-(4-Fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionic acid (exemplification No. 138-56 compound)
[1083] In a similar manner to that described in Example 2, ethyl
2-(4-fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionate (2.45 g), which is the product of Example 118, was reacted
with aqueous sodium hydroxide solution (1N, 15.0 ml) and the
reaction mixture was treated to give the title compound (2.30 g) as
a white powder.
[1084] mp 139-140.5.degree. C.
[1085] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.20 (2H, d,
J=6.5 Hz), 3.80-3.91 (2H, m), 4.16-4.22 (2H, m), 4.74 (1H, t, J=6.5
Hz), 6.69-6.77 (1H, m), 6.77-6.92 (6H, m), 7.19 (2H, d, J=8.5 Hz),
7.30-7.37 (1H, m), 7.69-7.80 (3H, m), 7.80-7.90 (3H, m), 8.71 (1H,
d, J=4.0 Hz).
EXAMPLE 120
Ethyl
2-(4-chlorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylaminoethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 138-72
compound)
[1086] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
chlorophenoxy)propionate (1.23 g), which is the product of
Reference example 38, 4-pyridine-2-ylbenzoic acid (539 mg), diethyl
cyanophosphonate (0.41 ml) and triethylamine (0.68 ml) and the
reaction mixture was treated to give the title compound (977 mg) as
colorless crystals.
[1087] mp 134-135.degree. C.
[1088] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 3.83-3.92 (2H, m), 4.08-4.21
(4H, m), 4.69 (1H, t, J=6.5 Hz), 6.60-6.68 (1H, m), 6.75 (2H, d,
J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 7.13-7.30 (5H, m), 7.72-7.79
(2H, m), 7.89 (2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.70-8.73
(1H, m).
EXAMPLE 121
2-(4-Chlorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionic acid (exemplification No. 138-72 compound)
[1089] In a similar manner to that described in Example 2, ethyl
2-(4-chlorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionate (950 mg), which is the product of Example 120, was reacted
with aqueous sodium hydroxide solution (1N, 3.49 ml) and the
reaction mixture was treated to give the title compound (834 mg) as
colorless crystals.
[1090] mp 155-156.degree. C.
[1091] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.21 (2H, d,
J=6.0 Hz), 3.80-3.90 (2H, m), 4.12-4.22 (2H, m), 4.76 (1H, t, J=6.0
Hz), 6.70-6.88 (5H, m), 7.15 (2H, d, J=8.5 Hz), 7.20 (2H, d, J=8.5
Hz), 7.30-7.38 (1H, m), 7.79-7.90 (6H, m), 8.70-8.74 (1H, m).
EXAMPLE 122
Ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluorome-
thylphenoxy)propionate (ethyl ester of exemplification No. 138-24
compound)
[1092] A solution of diethyl azodicarboxylate (40% toluene
solution, 0.52 ml) in toluene (3.0 ml) was added dropwise to a
solution of ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(332 mg), which is the product of Reference example 39,
4-trifluoromethylphenol (186 mg) and triphenylphosphine (300 mg) in
toluene (10 ml) at ambient temperature. After the mixture was
stirred for 2 hours at ambient temperature, triphenylphosphine (100
mg) and diethyl azocarboxylate (40% toluene solution, 0.19 ml) were
added to the reaction mixture. The mixture was stirred for 18
hours. The reaction mixture was concentrated under reduced
pressure. The residue was purified via chromatography on a silica
gel column using dichloromethane/ethyl acetate=3/2 as the eluant to
give the title compound (283 mg, containing some contaminants) as a
white powder.
[1093] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.21 (2H, d, J=6.5 Hz), 3.89 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.21 (2H, q, J=7.0 Hz), 4.77 (1H, t, J=6.5 Hz),
6.66 (1H, brt), 6.88 (2H, d, J=8.5 Hz), 6.90 (2H, d, J=8.5 Hz),
7.23 (2H, d, J=8.5 Hz), 7.26-7.34 (1H, m), 7.49 (2H, d, J=8.5 Hz),
7.75-7.83 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz),
8.72 (1H, d, J=5.0 Hz).
EXAMPLE 123
3-[4-[2-(4-Pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluoromethylph-
enoxy)propionic acid (exemplification No. 138-24 compound)
[1094] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluoromethylp-
henoxy)propionate (269 mg), which is the product of Example 122,
was reacted with aqueous sodium hydroxide solution (1N, 0.55 ml)
and the reaction mixture was treated to give the title compound
(138 mg) as a white powder.
[1095] mp 154-155.degree. C.
[1096] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.02 (1H, dd, J=5.0, 13.5 Hz), 3.16 (1H, dd, J=2.0,
13.5 Hz), 3.63 (2H, q, J=5.5 Hz), 4.10 (2H, t, J=5.5 Hz), 4.64 (1H,
dd, J=2.0, 5.0 Hz), 6.88 (2H, d, J=8.5 Hz), 6.95 (2H, d, J=8.5 Hz),
7.23 (2H, d, J=8.0 Hz), 7.41 (1H, dd, J=6.0, 7.5 Hz), 7.54 (2H, d,
J=8.5 Hz), 7.88-7.97 (1H, m), 7.98 (2H, d, J=8.5 Hz), 8.05 (1H, d,
J=7.5 Hz), 8.18 (2H, d, J=8.0 Hz), 8.70 (1H, d, J=3.5 Hz), 8.78
(1H, brt).
EXAMPLE 124
Ethyl
2-(4-methoxyphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate (ethyl ester of exemplification No. 8-35
compound)
[1097] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (433 mg), which is the product of
Reference example 39, 4-methoxyphenol (247 mg), triphenylphosphine
(523 mg) and diethyl azodicarboxylate (40% toluene solution, 0.65
ml) and the reaction mixture was treated to give the title compound
(320 mg) as a yellow oil.
[1098] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17 (2H d, J=6.5 Hz), 3.72 (3H, s), 3.89 (2H, q, J=5.5
Hz), 4.10-4.21 (4H m), 4.63 (1H, t, J=6.5 Hz), 6.66 (1H, t, J=5.5
Hz). 6.87 (2H, d, J=8.5 Hz), 7.23 (2H, d, J=8.5 Hz), 7.23-7.30 (1H,
m), 7.40-7.70 (4H, m), 7.75-7.80 (2H, m), 7.88 (2H, d, J=8.5 Hz),
8.08 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 125
2-(4-Methoxyphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionic acid (exemplification No. 8-35 compound)
[1099] In a similar manner to that described in Example 2, ethyl
2-(4-methoxyphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]p-
ropionate (310 mg), which is the product of Example 124, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (50 mg)
as a white powder.
[1100] mp 67.5-70.degree. C.
[1101] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.20 (2H, d,
J=6.0 Hz), 3.73 (3H, s), 3.82-3.92 (2H, m), 4.16-4.25 (2H, m), 4.74
(1H, t, J=6.5 Hz), 6.65-6.90 (7H, m), 7.21 (2H, d, J=8.5 Hz),
7.27-7.37 (1H, m), 7.70-7.89 (4H, m), 7.93 (2H, d, J=8.5 Hz), 8.72
(1H, d, J=5.0 Hz).
EXAMPLE 126
Ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluorome-
thoxy-phenoxy)propionate (ethyl ester of exemplification No. 138-40
compound)
[1102] Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-trifluoromet-
hoxyphenoxy)propionate (2.11 g), which is the product of Reference
Example 40, was dissolved in a dioxane solution of hydrogen
chloride (4N, 30 ml). The mixture was allowed to stand for 40
minutes at ambient temperature. After, the reaction mixture was
concentrated under reduced pressure and the hydrogen chloride was
azeotropically evaporated with toluene. The residue, which is ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-trifluoromethoxy-
phenoxy)propionate hydrogen chloride, and
4-pyridine-2-ylbenzoylchloride hydrochloride (1.25 g) were
suspended in dichloromethane (70 ml). To this suspension,
triethylamine (2.28 ml) was added in an ice bath and the mixture
was stirred for 1 hour at the same temperature. The reaction
mixture was concentrated under reduced pressure. The residue was
partitioned between ethyl acetate and water and the ethyl acetate
layer was separated and washed with saturated aqueous sodium
chloride solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatograpy on silica gel column using hexane/ethyl acetate 2/3
as the eluant to give the title compound (1.75 g) as colorless
crystals.
[1103] mp 87-88.degree. C.
[1104] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.17 (3H, t,
J=7.0 Hz), 3.18 (2H, d, J=6.5 Hz), 3.89 (2H, q, J=5.0 Hz),
4.10-4.25 (4H, m), 4.70 (1H, t, J=6.5 Hz), 6.65 (1H, brt), 6.81
(2H, d, J=8.5 Hz), 6.88 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz),
7.14-7.31 (1H, m), 7.23 (2H, d, J=8.5 Hz), 7.72-7.82 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5
Hz).
EXAMPLE 127
3-[4-[2-(4-Pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluoromethoxyp-
henoxy)propionic acid (exemplification No.138-40 compound)
[1105] In a similar manner to that described in Example 2, ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(4-trifluoromethoxy-
phenoxy)propionate (1.65 g), which is the product of Example 126,
was reacted with aqueous sodium hydroxide solution (1N, 5.54 ml)
and the reaction mixture was treated to give the title compound
(1.33 g) as colorless crystals.
[1106] mp 180-181.degree. C.
[1107] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 3.16
(1H, dd, J=8.0, 14.5 Hz), 3.22 (1H, dd, J=4.5, 14.5 Hz), 3.78 (2H,
q, J=5.5 Hz), 4.16 (2H, t, J=5.5 Hz), 4.83 (1H, dd, J=4.5, 8.0 Hz),
6.89 (2H, d, J=8.5 Hz), 6.91 (2H, d, J=8.5 Hz), 7.13 (2H, d, J=8.5
Hz), 7.24 (2H, d, J=8.5 Hz), 7.36-7.45 (1H, m), 7.88-7.99 (2H, m),
7.94 (2H, d, J=8.5 Hz), 8.05 (2H, d, J=8.5 Hz), 8.64 (1H, d, J=5.0
Hz), 8.77 (1H, brt).
EXAMPLE 128
Ethyl
2-(4-cyanophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 138-104
compound)
[1108] In a similar manner to that described in Example 126, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-
-(4-cyanophenoxy)propionate (237 mg), which is the product of
Reference Example 41, 4-pyridine-2-ylbenzoylchloride hydrochloride
(131 mg) and triethylamine (0.29 ml) and the reaction mixture was
treated to give the title compound (244 mg) as a syrup.
[1109] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.21 (2H, d, J=6.5 Hz), 3.89 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.79 (1H, t, J=6.5 Hz),
6.65 (1H, brt), 6.88 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz),
7.24-7.31 (1H, m), 7.54 (2H, d, J=8.5 Hz), 7.70-7.84 (2H, m). 7.88
(2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0
Hz).
EXAMPLE 129
2-(4-Cyanophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionic acid (exemplification No. 138-104 compound)
[1110] In a similar manner to that described in Example 2, ethyl
2-(4-cyanophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate (244 mg), which is the product of Example 128, was reacted
with aqueous sodium hydroxide solution (1N, 0.92 ml) and the
reaction mixture was treated to give the title compound (184 mg) as
colorless crystals.
[1111] mp 92-93.degree. C.
[1112] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 3.24
(2H, d, J=6.0 Hz), 3.86 (2H, q, J=5.5 Hz), 4.15-4.25 (2H, m), 4.85
(1H, t, J=6.0 Hz), 6.76 (1H, brt), 6.85 (2H, d, J=8.0 Hz), 6.91
(2H, d, J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz), 7.37 (1H, dd, J=5.0, 6.0
Hz), 7.48 (2H, d, J=7.5 Hz), 7.73 (3H, d, J=8.0 Hz), 7.84 (2H, d,
J=7.5 Hz), 7.87 (1H, dd, J=6.0, 8.0 Hz), 8.71 (1H, d, J=5.0
Hz).
EXAMPLE 130
Methyl
2-(4-methylthiophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy-
]phenyl]propionate (methyl ester of exemplification No. 138-120
compound)
[1113] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]--
2-(4-methylthiophenoxy)propionate (265 mg), which is the product of
Reference Example 42, 4-pyridine-2-ylbenzoylchloride hydrochloride
(175 mg) and triethylamine (0.32 ml) and the reaction mixture was
treated to give the title compound (164 mg) as colorless
crystals.
[1114] mp 94-95.degree. C.
[1115] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.41 (3H, s),
3.17 (2H, d, J=6.5 Hz), 3.71 (3H, s), 3.89 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.72 (1H, t, J=6.5 Hz), 6.66 (1H, brt), 6.77
(2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz),
7.21 (2H, d, J=8.0 Hz), 7.23-7.30 (1H, m), 7.73-7.84 (2H, m), 7.88
(2H, d, J=8.0 Hz), 8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5
Hz).
EXAMPLE 131
2-(4-Methylthiophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl-
]propionic acid (exemplification No.138-120 compound)
[1116] In a similar manner to that described in Example 2, methyl
2-(4-methylthiophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (203 mg), which is the product of Example 130, was
reacted with aqueous sodium hydroxide solution (1N, 0.74 ml) and
the reaction mixture was treated to give the title compound (153
mg) as colorless crystals.
[1117] mp 168-169.degree. C.
[1118] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.40 (3H, s),
3.22 (2H, d, J=6.0 Hz), 3.87 (2H, q, J=5.0 Hz), 4.21 (2H, t, J=5.0
Hz), 4.80 (1H, t, J=6.0 Hz), 6.72 (1H, brt), 6.84 (2H, d, J=8.5
Hz), 6.86 (2H, d, J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz), 7.21 (2H, d,
J=8.5 Hz), 7.34 (1H, dd, J=5.0, 7.0 Hz), 7.74 (1H, dd, J=7.0, 7.5
Hz), 7.75 (2H, d, J=8.5 Hz), 7.83 (1H, d, J=7.5 Hz), 7.90 (2H, d,
J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 132
Methyl
2-(4-methanesulfonylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)e-
thoxy]phenyl]propionate (methyl ester of exemplification No.
138-136 compound)
[1119] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]--
2-(4-methanesulfonylphenoxy)propionate (387 mg), which is the
product of Reference example 43, 4-pyridine-2-ylbenzoylchloride
hydrochloride (219 mg) and triethylamine (0.44 ml) and the reaction
mixture was treated to give the title compound (278 mg) as
colorless crystals.
[1120] mp 80-81.degree. C.
[1121] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.99 (3H, s),
3.23 (2H, d, J=6.5 Hz), 3.74 (3H, s), 3.89 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.85 (1H, t, J=6.5 Hz), 6.65 (1H, brt), 6.88
(2H, d, J=8.5 Hz), 6.94 (2H, d, J=9.0 Hz), 7.21 (2H, d, J=8.5 Hz),
7.23-7.38 (1H, m), 7.74-7.82 (2H, m), 7.82 (2H, d, J=9.0 Hz), 7.89
(2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.73 (1H, d, J=4.5
Hz).
EXAMPLE 133
2-(4-Methanesulfonylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]p-
henyl]propionic acid (exemplification No. 138-136 compound)
[1122] In a similar manner to that described in Example 2, methyl
2-(4-methanesulfonylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]-
phenyl]propionate (263 mg), which is the product of Example 132,
was reacted with aqueous sodium hydroxide solution (1N, 0.94 ml)
and the reaction mixture was treated to give the title compound
(195 mg) as colorless crystals.
[1123] mp 231-233.degree. C.
[1124] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.03-3.24 (2H, m), 313 (3H, s), 3.64 (2H, q, J=5.5 Hz),
4.10 (2H, t, J=5.5 Hz), 5.10 (1H, dd, J=4.5, 7.5 Hz), 6.90 (2H, d,
J=8.5 Hz), 7.07 (2H, d, J=9.0 Hz), 7.25 (2H, d, J=8.5 Hz), 7.40
(1H, dd, J=5.0, 7.5 Hz), 7.78 (2H, d, J=9.0 Hz), 7.92 (1H, dd,
J=7.5, 8.0 Hz), 7.98 (2H, d, J=8.5 Hz), 8.05 (1H, d, J=8.0 Hz),
8.18 (2H, d, J=8.5 Hz), 8.70 (1H, d, J=5.0 Hz), 8.78 (1H, t, J=5.5
Hz).
EXAMPLE 134
Ethyl
2-(4-pyridine-2-ylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)etho-
xy]phenyl]propionate (ethyl ester of exemplification No. 138-264
compound)
[1125] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (370 mg), which is the product of
Reference example 39, 4-(pyridine-2-yl)phenol (292 mg),
triphenylphosphine (447 mg) and diethyl azodicarboxylate (40%
toluene solution, 0.56 ml) and the reaction mixture was treated to
give the title compound (500 mg) as a colorless oil.
[1126] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.22 (2H, d, J=6.0 Hz), 3.89 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.82 (1H, t, J=6.0 Hz),
6.66 (1H, t, J=5.0 Hz), 6.88 (2H, d, J=8.5 Hz), 7.93 (2H, d, J=8.5
Hz), 7.10-7.30 (3H, m), 7.45-7.80 (5H, m), 7.89 (4H, d, J=8.5 Hz),
8.07 (2H, d, J=8.5 Hz), 8.63 (1H, d, J=4.5 Hz), 8.71 (1H, d, J=4.5
Hz).
EXAMPLE 135
2-(4-Pyridine-2-ylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionic acid (exemplification No. 138-264 compound)
[1127] In a similar manner to that described in Example 2, ethyl
2-(4-pyridine-2-ylphenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]ph-
enyl]propionate (500 mg), which is the product of Example 134, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (390
mg) as a white powder.
[1128] mp 98-101.degree. C.
[1129] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.08-3.22 (2H, m), 3.60-3.70 (2H, m), 4.05-4.15 (2H,
m), 4.90-5.00 (1H, m), 6.92 (2H, d, J=7.5 Hz), 6.95 (2H, d, J=8.5
Hz), 7.27 (3H, d, J=7.5 Hz), 7.40 (1H, t, J=6.0 Hz), 7.50-7.70 (1H,
m), 7.77-8.10 (7H, m), 8.18 (2H, d, J=7.5 Hz), 8.60 (1H, d, J=4.0
Hz), 8.70 (1H, d, J=5.0 Hz), 8.75-8.82 (1H, m).
EXAMPLE 136
Ethyl
2-(3-fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionate (ethyl ester of exemplification No. 138-88
compound)
[1130] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (500 mg), which is the product of
Reference example 39, 3-fluorophenol (258 mg), triphenylphosphine
(604 mg) and diethyl azodicarboxylate (40% toluene solution, 0.75
ml) and the reaction mixture was treated to give the title compound
(524 mg) as a white powder.
[1131] mp 133-134.5.degree. C.
[1132] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.18 (2H, d, J=6.5 Hz), 3.81-3.92 (2H, m), 4.10-422 (4H,
m), 4.72 (1H, t, J=6.5 Hz), 6.51-6.70 (4H, m), 6.88 (2H, d, J=8.5
Hz), 7.11-7.30 (4H, m), 7.71-7.82 (2H, m), 7.89 (2H, d, J=8.5 Hz),
8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 137
2-(3-Fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionic acid (exemplification No. 138-88 compound)
[1133] In a similar manner to that described in Example 2, ethyl
2-(3-fluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionate (500 mg), which is the product of Example 136, was reacted
with aqueous sodium hydroxide solution (1N, 2.00 ml) and the
reaction mixture was treated to give the title compound (410 mg) as
a white powder.
[1134] mp 136.5-138.degree. C.
[1135] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.00-3.20 (2H, m), 3.56-3.70 (2H, m), 4.01-4.12 (2H,
m), 4.90-5.00 (1H, m), 6.62-6.80 (3H, m), 6.91 (2H, d, J=8.5 Hz),
7.16-7.31 (3H, m), 7.37-7.43 (1H, m), 7.85-8.08 (4H, m), 8.19 (2H,
d, J=8.5 Hz), 8.70 (1H, d, J=5.0Hz), 8.71-8.82 (1H, m).
EXAMPLE 138
Ethyl 2-(3
,5-difluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy-
]phenyl]propionate (ethyl ester of exemplification No. 138-168
compound)
[1136] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (400 mg), which is the product of
Reference example 39, 3,5-difluorophenol (240 mg),
triphenylphosphine (483 mg) and diethyl azodicarboxylate (40%
toluene solution, 0.60 ml) and the reaction mixture was treated to
give the title compound (460 mg) as a white powder.
[1137] mp 146-147.degree. C.
[1138] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 3.18 (2H, d, J=6.5 Hz), 3.89 (2H, d, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.19(2H, q, J=7.0 Hz), 4.68 (1H, t, J=6.5 Hz),
6.31-6.45 (3H, m), 6.66 (1H, t, J=5.0 Hz), 6.86 (2H, d, J=8.5 Hz),
7.21 (2H, d, J=8.5 Hz), 7.26-7.31 (1H, m), 7.75-7.80 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0
Hz).
EXAMPLE 139
2-(3,5-Difluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl-
]propionic acid (exemplification No. 138-168 compound)
[1139] In a similar manner to that described in Example 2, ethyl
2-(3,5-difluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (410 mg), which is the product of Example 138, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (350
mg) as a white powder.
[1140] mp 149.5-151.degree. C.
[1141] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.05-3.25 (2H, m), 3.65 (2H, d, J=5.5 Hz), 4.11 (2H, t,
J=5.5 Hz), 5.08 (1H, t, J=5.5 Hz), 6.65 (2H, d, J=9.0 Hz),
6.70-6.83 (1H, m), 6.91 (2H, d, J=7.5 Hz), 7.23 (2H, d, J=7.5 Hz),
7.38-7.45 (1H, m), 7.90-8.10 (4H, m), 8.18 (2H, d, J=8.5 Hz), 8.70
(1H, d, J=4.5 Hz), 8.79 (1H, t, J=5.0 Hz).
EXAMPLE 140
Ethyl
2-(3,4-difluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]-
phenyl]propionate (ethyl ester of exemplification No. 138-152
compound)
[1142] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (312 mg), which is the product of
Reference example 39, 3,4-difluorophenol (187 mg),
triphenylphosphine (377 mg) and diethyl azodicarboxylate (40%
toluene solution, 0.65 ml) and the reaction mixture was treated to
give the title compound (213 mg) as a white powder.
[1143] mp 133-134.degree. C.
[1144] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 3.90 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.64 (1H, t, J=6.5 Hz),
6.48-6.60 (1H, m), 6.62-6.84 (2H, m), 6.88 (2H, d, J=8.5 Hz), 7.00
(1H, q, J=9.5 Hz), 7.21 (2H, d, J=8.5 Hz), 7.26-7.31 (1H, m),
7.72-7.82 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz),
8.72 (1H, d, J=5.0 Hz).
EXAMPLE 141
2-(3,4-Difluorophenoxy)-3-
[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny- l]propionic acid
(exemplification No. 138-152 compound)
[1145] In a similar manner to that described in Example 2, ethyl
2-(3,4-difluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (281 mg), which is the product of Example 140, was
reacted with aqueous sodium hydroxide solution (1N, 1.02 ml) and
the reaction mixture was treated to give the title compound (246
mg) as a white powder.
[1146] mp 135-136.degree. C.
[1147] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.20 (2H, d,
J=6.5 Hz), 3.80 (2H, q, J=5.5 Hz), 4.23 (2H, t, J=5.5 Hz), 4.73
(1H, t, J=6.5 Hz), 6.56-6.66 (1H, m), 6.68-6.77 (2H, m), 6.86 (2H,
d, J=8.5 Hz), 7.00 (1H, q, J=9.5 Hz), 7.19 (2H, d, J=8.5 Hz), 7.36
(1H, dd, J=5.5, 7.5 Hz), 7.74 (1H, d, J=7.5 Hz), 7.74 (2H, d, J=8.5
Hz), 7.84-7.87 (1H, m), 7.88 (2H, d, J=8.5 Hz), 8.71 (1H, d, J=4.5
Hz).
EXAMPLE 142
Ethyl
2-(3,4,5-trifluorophenoxy)-3-[4-[2-(4-pyridine-2-yl-benzoylamino)eth-
oxy]phenyl]propionate (ethyl ester of exemplification No. 138-184
compound)
[1148] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (385 mg), which is the product of
Reference example 39, 3,4,5-trifluorophenol (262 mg),
triphenylphosphine (465 mg) and diethyl azodicarboxylate (40%
toluene solution, 0.58 ml) and the reaction mixture was treated to
give the title compound (415 mg) as a white powder.
[1149] mp 150-152.degree. C.
[1150] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 3.16 (2H, d, J=6.5 Hz), 3.90 (2H, q, J=5.0 Hz), 4.16
(2H, t, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.62 (1H, t, J=6.5 Hz),
6.41-6.50 (2H, m), 6.66 (1H, t, J=5.0 Hz), 6.88 (2H, d, J=8.5 Hz),
7.20 (2H, d, J=8.5 Hz), 7.25-7.30 (1H, m), 7.73-7.81 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0
Hz).
EXAMPLE 143
2-(3,4,5-Trifluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionic acid (exemplification No. 138-184 compound)
[1151] In a similar manner to that described in Example 2, ethyl
2-(3,4,5-trifluorophenoxy)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]ph-
enyl]propionate (380 mg), which is the product of Example 142, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (320
mg) as a white powder.
[1152] mp 144-146.degree. C.
[1153] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.16-3.23
(2H, m), 3.80-3.90 (2H, m), 4.17-4.25 (2H, m), 4.66 (1H, t, J=6.0
Hz), 6.41-6.58 (2H, m), 6.75-6.82 (1H, m), 6.84 (2H, d, J=8.5 Hz),
7.17 (2H, d, J=8.5 Hz), 7.38 (1H, t, J=6.0 Hz), 7.70-7.90 (6H, m),
8.72 (1H, d, J=5.0 Hz).
EXAMPLE 144
Ethyl
2-pentafluorophenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate (ethyl ester of exemplification No. 138-200
compound)
[1154] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate (500 mg), which is the product of
Reference example 39, pentafluorophenol (424 mg),
triphenylphosphine (604 mg) and diethyl azodicarboxylate (40%
toluene solution, 1.10 ml) and the reaction mixture was treated to
give the title compound (918 mg, containing some concomitant) as a
white powder.
[1155] .sup.1H-NMR (270 MHz. CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 3.12-3.33 (2H, m), 3.82-3.94 (2H, m), 4.10-427 (4H, m),
4.91 (1H, dd, J=5.0, 7.5 Hz), 6.62-6.72 (1H, m), 6.88 (2H. d, J=8.5
Hz), 7.18-7.30 (3H, m), 7.70-7.80 (2H, m), 7.90 (2H, d, J=8.5 Hz),
8.08 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 145
2-Pentafluorophenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionic acid (exemplification No. 138-200 compound)
[1156] In a similar manner to that described in Example 2, ethyl
2-pentafluorophenoxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]p-
ropionate (910 mg), which is the product of Example 144, was
reacted with aqueous sodium hydroxide solution (1N, 2.00 ml) and
the reaction mixture was treated to give the title compound (240
mg) as a white powder.
[1157] mp 145-146.degree. C.
[1158] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.19-3.41
(2H, m), 3.75-4.10 (2H, m), 4.21-432 (2H, m), 5.04 (1H, t, J=6.0
Hz), 6.70-6.85 (1H, m), 6.90 (2H, d, J=8.5 Hz), 7.26 (2H, d, J=8.5
Hz), 7.38-7.46 (1H, m), 7.68-7.81 (3H, m), 7.81-7.98 (3H, m), 8.77
(1H, d, J=4.5 Hz).
EXAMPLE 146
Methyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-fluorophenoxy-
)propionate (methyl ester of exemplification No. 138-51
compound)
[1159] In a similar manner to that described in Example 73, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4- -fluorophenoxy)
propionate (314 mg), which is the product of Reference example 44,
biphenyl-4-carboxylic acid (158 mg), diethyl cyanophosphonate (0.12
ml) and triethylamine (0.30 ml) and the reaction mixture was
treated to give the title compound (276 mg) as a white powder.
[1160] mp 105-106.degree. C.
[1161] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.17 (2H, d,
J=6.5 Hz), 3.72 (3H, s), 3.89 (2H, q, J=5.0 Hz), 4.16 (2H, t, J=5.0
Hz), 4.68 (1H, t, J=6.5 Hz), 6.63 (1H, brt), 6.76 (2H, dd, J=4.0,
9.0 Hz), 6.88 (2H, d, J=8.5 Hz), 6.91 (2H, t, J=9.0 Hz), 7.22 (2H,
d, J=8.5 Hz), 7.41 (1H, t, J=7.0 Hz), 7.44 (1H, t, J=7.0 Hz), 7.47
(1H, t, J=7.0 Hz), 7.61 (2H, d, J=7.0 Hz), 7.66 (2H, d, J=8.5 Hz),
7.85 (2H, d, J=8.5 Hz).
EXAMPLE 147
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-fluorophenoxy)propio-
nic acid (exemplification No. 138-51 compound)
[1162] In a similar manner to that described in Example 2, methyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(4-fluorophenoxy)propi-
onate (266 mg), which is the product of Example 146, was reacted
with aqueous sodium hydroxide solution (1N, 1.04 ml) and the
reaction mixture was treated to give the title compound (241 mg) as
colorless crystals.
[1163] mp 162-163.degree. C.
[1164] .sup.1H-NMR (270 MHz, CDCl.sub.3/deuterated methanol=10/1):
.delta. ppm 3.19 (1H, d, J=7.5 Hz), 3.20 (1H, d, J=5.0 Hz), 3.87
(2H, q, J=5.0 Hz), 4.14 (2H, t, J=5.0 Hz), 4.66 (1H, dd, J=5.0, 7.5
Hz), 6.78 (2H, dd, J=4.5, 9.0 Hz), 6.87 (2H, d, J=8.5 Hz), 6.91
(2H, t, J=9.0 Hz), 7.24 (2H, d, J=8.5 Hz), 7.38 (1H, t, J=7.0 Hz),
7.43 (1H, t, J=7.0 Hz), 7.46 (1H, t, J=7.0 Hz), 7.60 (2H, d, J=7.0
Hz), 7.65 (2H, d, J=7.0 Hz), 7.85 (2H, d, J=8.5 Hz).
EXAMPLE 148
Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[6-(4-methoxyphenyl)pyridine-3-carbon-
ylamino]ethoxy]phenyl]-2-methylpropionate (ethyl ester of
exemplification No. 34-40 compound)
[1165] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)-2-methylpropionate (400 mg), which is the product
of Reference example 45 6-(4-methoxyphenyl)nicotinic acid (208 mg),
which is the product of Reference example 26, diethyl
cyanophosphonate (0.14 ml) and triethylamine (0.23 ml) and the
reaction mixture was treated to give the title compound (355 mg) as
colorless crystals.
[1166] mp 92-94.degree. C.
[1167] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.01-1.28
(9H, m), 1.36 (3H, s), 2.76-2.91 (1H, m), 3.10 (1H, d, J=14.0 Hz),
3.26 (1H, d, J=14.0 Hz), 3.87 (3H, s), 3.81-3.94 (2H, m), 4.10-4.27
(4H, m), 6.60-6.68 (1H, m), 6.75 (2H, d, J=8.5 Hz), 6.85 (2H, d,
J=8.5 Hz), 7.01 (2H, d, J=9.0 Hz), 7.06 (2H, d, J=8.5 Hz), 7.19
(2H, d, J=8.5 Hz), 7.74 (1H, d, J=8.5 Hz), 8.01 (2H, d, J=8.5 Hz),
8.13 (1H, dd, J=2.0, 8.5 Hz), 9.01 (1H, d, J=2.0 Hz).
EXAMPLE 149
2-(4-Isopropylphenoxy)-3-[4-[2-(2-(4-methoxyphenyl)pyridine-5-carbonylamin-
o]ethoxy]phenyl]-2-methylpropionic acid (exemplification No. 34-40
compound)
[1168] In a similar manner to that described in Example 2, ethyl
2-(4-isopropylphenoxy)-3-[4-[2-[2-(4-methoxyphenyl)pyridine-5-carbonylami-
no]ethoxy]phenyl]-2-methylpropionate (341 mg), which is the product
of Example 148, was reacted with aqueous sodium hydroxide solution
(1N, 1.14 ml) and the reaction mixture was treated to give the
title compound (144 mg) as colorless crystals.
[1169] mp 194-196.degree. C.
[1170] .sup.1-NMR (270 MHz, deuterated dimethyl sulfoxide): .delta.
ppm 1.15 (6H, d, J=7.0 Hz), 1.27 (3H, s), 2.72-2.89 (1H, m), 3.06
(1H, d, J=13.5 Hz), 3.17 (1H, d, J=13.5 Hz), 3.61-3.70 (2H, m),
3.83 (3H, s), 4.08-4.16 (2H, m), 6.74 (2H, d, J=8.5 Hz), 6.91 (2H,
d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 7.17
(2H, d, J=8.5 Hz), 8.01 (1H, d, J=8.5 Hz), 8.12 (2H, d, J=8.5 Hz),
8.24 (1H, dd, J=2.0, 8.5 Hz), 8.86-8.94 (1H, m), 9.05 (1H, d, J=2.0
Hz).
EXAMPLE 150
Ethyl
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino]etho-
xy]phenyl]2-(4-isopropylphenoxy)-2-methylpropionate (ethyl ester of
exemplification No. 34-43 compound)
[1171] In a similar manner to that described in Example 73, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4--
isopropylphenoxy)-2-methylpropionate (600 mg), which is the product
of Reference example 45, 6-(2,2,3,3-tetrafluoropropoxy)nicotinic
acid (344 mg), which is the product of Reference example 28,
diethyl cyanophosphonate (0.21 ml) and triethylamine (0.38 ml) and
the reaction mixture was treated to give the title compound (260
mg) as a colorless oil.
[1172] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 1.16-1.28
(9H, m), 1.37 (3H, s), 2.83 (1H, septet, J=7.0 Hz), 3.11 (1H, d,
J=13.5 Hz), 3.26 (1H, d, J=13.5 Hz), 3.83-3.89 (2H, m), 4.10-4.18
(2H, m), 4.21 (2H, q, J=7.0 Hz), 4.75 (2H, t, J=12.5 Hz), 6.00 (1H,
tt, J=4.5, 53 Hz), 6.53-6.60 (1H, m), 6.75 (2H, d, J=8.5 Hz),
6.81-6.90 (3H, m), 7.06 (2H, d, J=8.5 Hz), 7.19 (2H, d, J=8.5 Hz),
8.07 (1H, d, J=8.5 Hz), 8.59 (1H, s).
EXAMPLE 151
3-[4-[2-[2-(2,2,3,3-Tetrafluoropropoxy)pyridine-5-carbonylamino]ethoxy]phe-
nyl]-2-(4-isopropylphenoxy)-2-methylpropionic acid (exemplification
No. 34-43 compound)
[1173] In a similar manner to that described in Example 2, ethyl
3-[4-[2-[2-(2,2,3,3-tetrafluoropropoxy)pyridine-5-carbonylamino]ethoxy]ph-
enyl]-2-(4-isopropylphenoxy)-2-methylpropionate (210 mg), which is
the product of Example 150, was reacted with aqueous sodium
hydroxide solution (1N, 0.51 ml) and the reaction mixture was
treated to give the title compound (140 mg) as colorless
crystals.
[1174] mp 173-175.degree. C.
[1175] .sup.1H-NMR (400 MHz, CDCl.sub.3/deuterated methanol=20/1):
.delta. ppm 1.20 (6H, d, J=7.0 Hz), 1.40 (3H, s), 2.84 (1H, septet,
J=7.0 Hz), 3.13 (1H, d, J=14.0 Hz), 3.26 (1H, d, J=14.0 Hz),
3.80-3.89 (2H, m), 4.14-4.20 (2H, m), 4.78 (2H, t, J=12.5 Hz), 6.00
(1H, tt, J=4.5, 53 Hz), 6.80-6.92 (5H, m), 7.09 (2H, d, J=8.5 Hz),
7.22 (2H, d, J=8.5 Hz), 8.09 (1H, d, J=8.5 Hz), 8.55 (1H, s).
EXAMPLE 152
Methyl
2-phenylthio-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate (methyl ester of exemplification No. 17-11 compound)
[1176] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]--
2-phenylthiopropionate (209 mg), which is the product of Reference
example 46, 4-pyridine-2-ylbenzoylchloride hydrochloride (135 mg)
and triethylamine (0.27 ml) and the reaction mixture was treated to
give the title compound (146 mg) as colorless crystals.
[1177] mp 102-104.degree. C.
[1178] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.00 (1H, dd,
J=6.0, 13.5 Hz), 3.14 (1H, dd, J=9.0, 13.5 Hz), 3.58 (3H, s), 3.86
(1H, dd, J=6.0, 9.0 Hz), 3.90 (2H, q, J=5.0 Hz), 4.15 (2H, t, J=5.0
Hz), 6.65 (1H, brt), 6.85 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5
Hz), 7.16-7.37 (4H, m), 7.38-7.48 (2H, m), 7.71-7.81 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.05 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0
Hz).
EXAMPLE 153
2-Phenylthio-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 17-11 compound)
[1179] In a similar manner to that described in Example 2, methyl
2-phenylthio-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionat-
e (150 mg), which is the product of Example 152, was reacted with
aqueous sodium hydroxide solution (1N, 0.58 ml) and the reaction
mixture was treated to give the title compound (138 mg) as
colorless crystals.
[1180] mp 75-77.degree. C.
[1181] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.00 (1H, dd,
J=5.0, 13.5 Hz), 3.11 (1H, dd, J=10.5, 13.5 Hz), 3.82 (2H, t, J=5.0
Hz), 3.87 (1H, dd, J=5.0, 10.5 Hz), 4.24 (1H, dd, J=5.0, 9.5 Hz),
4.33 (1H, dd, J=5.0, 9.5 Hz), 6.53 (1H, brt), 6.84 (2H, d, J=8.5
Hz), 7.09 (2H, d, J=8.5 Hz), 7.27-7.38 (4H, m), 7.51-7.54 (2H, m),
7.61 (2H, d, J=8.5 Hz), 7.71 (1H, d, J=8.0 Hz), 7.82-7.89 (1H, m),
7.87 (2H, d, J=8.5 Hz), 8.63 (1H, d, J=5.0 Hz).
EXAMPLE 154
Methyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyridine-3-y-
loxy)propionate (methyl ester of exemplification No. 138-216
compound)
[1182] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]--
2-(pyridine-3-yloxy)propionate (345 mg), which is the product of
Reference example 47, 4-pyridine-2-ylbenzoylchloride hydrochloride
(261 mg) and triethylamine (0.60 ml) and the reaction mixture was
treated to give the title compound (271 mg) as colorless
crystals.
[1183] mp 101-103.degree. C.
[1184] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.22 (2H, d,
J=6.5 Hz), 3.73 (3H, s), 3.90 (2H, q, J=5.0 Hz), 4.16 (2H, t, J=5.0
Hz), 4.78 (1H, t, J=6.5 Hz), 6.66 (1H, brt), 6.88 (2H, d, J=8.5
Hz), 7.09-7.18 (2H, m), 7.22 (2H, d, J=8.5 Hz), 7.26-7.33 (1H, m),
7.73-7.82 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz),
8.16-8.26 (2H, m), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 155
3- [4-
[2-(4-Pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyridine-3-yloxy)-
propionic acid (exemplification No. 138-216 compound)
[1185] In a similar manner to that described in Example 2, methyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyridine-3-yloxy)p-
ropionate (248 mg), which is the product of Example 154, was
reacted with aqueous sodium hydroxide solution (1N, 1.00 ml) and
the reaction mixture was treated to give the title compound (212
mg) as colorless crystals.
[1186] mp 194-196.degree. C.
[1187] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.10 (1H, dd, J=8.5, 14.5 Hz), 3.18 (1H, dd, J=4.0,
14.5 Hz), 3.64 (2H, q, J=5.5 Hz), 4.10 (2H, t, J=5.5 Hz), 5.04 (1H,
dd, J=4.0, 8.5 Hz), 6.91 (2H, d, J=8.5 Hz), 7.25 (2H, d, J=8.5 Hz),
7.26 (1H, dd, J=6.5, 8.0 Hz), 7.27 (1H, d, J=6.5 Hz), 7.40 (1H, dd,
J=4.5, 8.0 Hz), 7.92 (1H, t, J=8.0 Hz), 7.98 (2H, d, J=8.5 Hz),
8.05 (1H, d, J=8.0 Hz), 8.14 (1H, s), 8.18 (2H, d, J=8.5 Hz), 8.18
(1H, d, J=8.0 Hz), 8.70 (1H, d, J=4.5 Hz), 8.79 (1H, brt).
EXAMPLE 156
Methyl
2-(Benzoxazole-2-ylthio)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethox-
y]phenyl]propionate (methyl ester of exemplification No. 138-248
compound)
[1188] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
2-(benzoxazole-2-ylthio)-3-[4-(2-t-butoxycar-
bonylaminoethoxy)phenyl]propionate (665 mg), which is the product
of Reference example 48, 4-pyridine-2-ylbenzoylchloride
hydrochloride (444 mg) and triethylamine (0.81 ml) and the reaction
mixture was treated to give the title compound (582 mg) as a mass
of foam.
[1189] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.30 (1H, dd,
J=7.5, 15.0 Hz), 3.35 (1H, dd, J=7.5, 15.0 Hz), 3.71 (3H, s), 3.88
(2H, q, J=5.0 Hz), 4.13 (2H, t, J=5.0 Hz), 4.77 (1H, t, J=7.5 Hz),
6.68 (1H, brt), 6.86 (2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz),
7.24-7.38 (3H, m), 7.42 (1H, d, J=7.5 Hz), 7.60 (1H, d, J=6.0 Hz),
7.75-7.82 (2H, m), 7.89 (2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz),
8.72 (1H, d, J=5.0 Hz).
EXAMPLE 157
2-(Benzoxazole-2-ylthio)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionic acid (exemplification No. 138-248 compound)
[1190] In a similar manner to that described in Example 2, methyl
2-(benzoxazole-2-ylthio)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionate (361 mg), which is the product of Example 156, was
reacted with aqueous sodium hydroxide solution (1N, 1.30 ml) and
the reaction mixture was treated to give the title compound (248
mg) as colorless crystals.
[1191] mp 66-67.degree. C.
[1192] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm
3.20-3.36 (2H, m), 3.75 (2H, t, J=5.5 Hz), 4.10 (1H, t, J=5.5 Hz),
4.19 (1H, t, J=5.5 Hz), 6.85 (1H, d, J=8.5 Hz), 6.89 (1H, d, J=8.5
Hz), 7.15 (1H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 7.28 (1H, t,
J=4.5 Hz), 7.40 (1H, dd, J=4.5, 8.5 Hz), 7.48 (1H, dd, J=4.0, 5.0
Hz), 7.54 (1H, dd, J=4.0, 5.0 Hz), 7.92 (2H, d, J=4.0 Hz), 7.95
(2H, d, J=8.5 Hz), 8.06 (2H, d, J=8.5 Hz), 8.64 (1H, d, J=4.5
Hz).
EXAMPLE 158
Methyl
2-benzyloxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionate (methyl ester of exemplification No. 138-232 compound)
[1193] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
2-benzyloxy-3-[4-(2-t-butoxycarbonylaminoeth- oxy)phenyl]propionate
(195 mg), which is the product of Reference example 49,
4-pyridine-2-ylbenzoylchloride hydrochloride (127 mg) and
triethylamine (0.25 ml) and the reaction mixture was treated to
give the title compound (106 mg) as colorless crystals.
[1194] mp 122-123.degree. C.
[1195] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.00 (1H, d,
J=7.5 Hz), 3.01 (1H, d, J=5.5 Hz), 3.71 (3H, s), 3.91 (2H, q, J=5.0
Hz), 4.10 (1H, dd, J=5.5, 7.5 Hz), 4.17 (2H, t, J=5.0 Hz), 4.37
(1H, d, J=12.0 Hz), 4.66 (1H, d, J=12.0 Hz), 6.68 (1H, brt), 6.86
(2H, d, J=8.5 Hz), 7.15 (2H, d, J=8.5 Hz), 7.19 (2H, d, J=8.0 Hz),
7.22-7.37 (4H, m), 7.76-7.83 (2H, m), 7.90 (2H, d, J=8.5 Hz), 8.08
(2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 159
2-Benzyloxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 138-232 compound)
[1196] In a similar manner to that described in Example 2, methyl
2-benzyloxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(94 mg), which is the product of Example 158, was reacted with
aqueous sodium hydroxide solution (1N, 0.36 ml) and the reaction
mixture was treated to give the title compound (86 mg) as colorless
crystals.
[1197] mp 138-139.degree. C.
[1198] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.01 (1H, dd,
J=7.0, 14.5 Hz), 3.12 (1H, dd, J=5.0, 14.5 Hz), 3.90 (2H, q, J=5.5
Hz), 4.18 (1H, dd, J=5.0, 7.0 Hz), 4.20 (2H, t, J=5.5 Hz), 4.48
(1H, d, J=1 1.5 Hz), 4.67 (1H, d, J=11.5 Hz), 6.69 (1H, brt), 6.85
(2H, d, J=8.5 Hz), 7.16 (2H, d, J=8.5 Hz), 7.22-7.43 (6H, m), 7.75
(1H, d, J=8.0 Hz), 7.79 (1H, dd, J=8.0, 9.0 Hz), 7.81 (2H, d, J=8.5
Hz), 8.00 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 160
2-(3-Phenylpropyl)-2-[4-[3-(4-pyridine-2-ylbenzoylamino)propyl]phenyl]prop-
ionic acid (exemplification No. 77-3 compound)
[1199] Palladium on carbon (5%, 0.12 g) was added to a solution of
dibenzyl
2-(3-phenylpropyl)-2-[4-[3-(4-pyridine-2-ylbenzoylamino)propyl]b-
enzyl]malonate (0.65 g), which is the product of Reference example
50, in ethanol (20 ml). The mixture was stirred under an atmosphere
of hydrogen at 60.degree. C. for 5 hours. After the catalyst was
removed by filtration, the filtrate was concentrated. The residue
was dissolved in 2-methoxyethanol (10 ml). The solution was stirred
at 150.degree. C. for 4 hours and then was concentrated. The
residue was purified via chromatography on a silica gel column
using dichloromethane/methanol=9/1 as the eluant to give the title
compound (330 mg) as crystals.
[1200] mp 118-119.degree. C.
[1201] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.75-1.82
(4H, m), 1.99 (2H, quintuplet, J=7.5 Hz), 2.58-2.77 (6H, m), 2.96
(1H, dd, J=11.0, 15.0 Hz), 3.51 (2H, dt, J=5.5, 7.5 Hz), 6.16 (1H,
brt, J=5.5 Hz), 7.12-7.18 (6H, m), 7.23-7.33 (4H, m), 7.60 (2H, d,
J=8.0 Hz), 7.71 (1H, dd, J=1.0, 8.0 Hz), 7.80 (1H, dd, J=2.0, 8.0
Hz), 7.93 (2H, d, J=8.5 Hz), 8.65-8.67 (1H, m).
EXAMPLE 161
Ethyl
3-[3-chloro-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-pheno-
xypropionate (ethyl ester of exemplification No. 139-24
compound)
[1202] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)-3-chlor- ophenyl]-
2-phenoxypropionate (738 mg), which is the product of Reference
example 51, 4-pyridine-2-ylbenzoylchloride hydrochloride (445 mg)
and triethylamine (0.89 ml) and the reaction mixture was treated to
give the title compound (677 mg) as a mass of foam.
[1203] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.16 (1H, d, J=5.5 Hz), 3.17 (1H, d, J=7.0 Hz), 3.93
(2H, q, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.22 (2H, t, J=5.0 Hz),
4.73 (1H, dd, J=5.5, 7.0 Hz), 6.83 (2H, d, J=8.5 Hz), 6.91 (1H, d,
J=8.5 Hz), 6.95 (1H, t, J=8.0 Hz), 7.18 (1H, dd, J=2.0, 8.5 Hz),
7.24 (2H, t, J=8.0 Hz), 7.26-7.33 (1H, m), 7.35 (1H, d, J=2.0 Hz),
7.77-7.85 (2H, m), 7.85 (2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz),
8.72 (1H, d, J=4.5 Hz).
EXAMPLE 162
3-[3-chloro-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxyprop-
ionic acid (exemplification No. 139-24 compound)
[1204] In a similar manner to that described in Example 2, ethyl
3-[3-chloro-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxypro-
pionate (540 mg), which is the product of Example 161, was reacted
with aqueous sodium hydroxide solution (1N, 1.98 ml) and the
reaction mixture was treated to give the title compound (404 mg) as
colorless crystals.
[1205] mp 59-61.degree. C.
[1206] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.19 (2H, d,
J=6.0 Hz), 3.83-3.98 (2H, m), 4.23 (2H, brt), 4.79 (1H, t, J=6.0
Hz), 6.86 (2H, d, J=8.0 Hz), 6.87 (1H, d, J=8.5 Hz), 6.93 (I1H, t,
J=8.0 Hz), 7.12 (1H, dd, J=2.0, 8.5 Hz), 7.23 (2H, t, J=8.0 Hz),
7.33 (1H, dd, J=4.5, 7.5 Hz), 7.36 (1H, d, J=2.0 Hz), 7.72 (1H, d,
J=8.0 Hz), 7.80 (2H, d, J=8.5 Hz), 7.84 (1H, dd, J=7.5, 8.0 Hz),
7.91 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5 Hz).
EXAMPLE 163
Ethyl
3-[3-bromo-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenox-
ypropionate (ethyl ester of exemplification No. 141-23
compound)
[1207] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[3-bromo-4-(2-t-butoxycarbonylaminoethoxy)-
phenyl]-2-phenoxypropionate (466 mg), which is the product of
Reference example 52, 4-pyridine-2-ylbenzoylchloride hydrochloride
(254 mg) and triethylamine (0.51 ml) and the reaction mixture was
treated to give the title compound (498 mg) as a mass of foam.
[1208] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 3.16 (1H, d, J=5.5 Hz), 3.17 (1H, d, J=7.0 Hz), 3.94
(2H, q, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.22 (2H, t, J=5.0 Hz),
4.73 (1H, dd, J=5.5, 7.0 Hz), 6.82-6.98 ( 1H, m), 6.83 (2H, d,
J=8.5 Hz), 6.88 (1H, d, J=8.5 Hz), 6.95 (1H, t, J=7.5 Hz),
7.21-7.32 (1H, m), 7.24 (2H, dd, J=7.5, 8.0 Hz), 7.25 (1H, dd,
J=2.0, 8.5 Hz), 7.52 (1H, d, J=2.0 Hz), 7.76-7.80 (2H, m), 7.95
(2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=4.5
Hz).
EXAMPLE 164
3-[3-Bromo-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxypropi-
onic acid (exemplification No. 141-23 compound)
[1209] In a similar manner to that described in Example 2, ethyl
3-[3-bromo-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxyprop-
ionate (237 mg), which is the product of Example 163, was reacted
with aqueous sodium hydroxide solution (1N, 0.80 ml) and the
reaction mixture was treated to give the title compound (174 mg) as
colorless crystals.
[1210] mp 83-84.degree. C.
[1211] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 3.12
(1H, dd, J=7.5, 14.0 Hz), 3.20 (1H, dd, J=5.0, 14.0 Hz), 3.81 (2H,
t, J=5.5 Hz), 4.24 (2H, t, J=5.5 Hz), 4.86 (1H, dd, J=5.0. 7.5 Hz),
6.84 (2H, d, J=8.0 Hz), 6.91 (1H, t, J=7.5 Hz), 7.02 (1H, d, J=8.5
Hz), 7.17 (1H, d, J=8.0 Hz), 7.22 (2H, dd, J=7.5, 8.0 Hz), 7.26
(1H, dd, J=2.0, 8.5 Hz). 7.40 (1H, dd, J=4.5, 8.0 Hz), 7.52 (1H, d,
J=2.0 Hz), 7.93 (1H, t, J=4.5 Hz), 7.95 (2H, d, J=8.5 Hz), 8.05
(2H, d, J=8.5 Hz), 8.64 (1H, d, J=4.5 Hz).
EXAMPLE 165
Ethyl
3-[3-nitro-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenox-
ypropionate (ethyl ester of exemplification No. 142-23
compound)
[1212] In a similar manner to that described in Example 126, a
reaction was carried out using methyl
3-[3-nitro-4-(2-t-butoxycarbonylaminoethoxy)-
phenyl]-2-phenoxypropionate (723 mg), which is the product of
Reference example 53, 4-pyridine-2-ylbenzoylchloride hydrochloride
(465 mg) and triethylamine (0.85 ml) and the reaction mixture was
treated to give the title compound (843 mg) as a mass of foam.
[1213] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 3.24 (2H, d, J=6.0 Hz), 3.96 (2H, q, J=5.0 Hz), 4.21
(2H, q, J=7.0 Hz), 4.31 (2H, t, J=5.0 Hz), 4.76 (1H, t, J=6.0 Hz),
6.83 (2H, d, J=8.5 Hz), 6.96 (1H, t, J=7.5 Hz), 7.05 (1H, d, J=8.5
Hz), 7.09 (1H, brt), 7.22-7.30 (1H, m), 7.24 (2H, dd, J=7.5, 8.0
Hz), 7.53 (1H, dd, J=2.5, 8.5 Hz), 7.75-7.80 (2H, m), 7.88 (1H, d,
J=2.5 Hz), 7.97 (2H, d, J=8.5 Hz), 8.09 (2H d, J=8.5 Hz), 8.72 (1H,
d, J=4.5 Hz).
EXAMPLE 166
3-[3-Nitro-4-
[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxyprop- ionic
acid (exemplification No. 142-23 compound)
[1214] In a similar manner to that described in Example 2, ethyl
3-[3-nitro-4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-phenoxyprop-
ionate (223 mg), which is the product of Example 165, was reacted
with aqueous sodium hydroxide solution (1N, 0.80 ml) and the
reaction mixture was treated to give the title compound (137 mg) as
colorless crystals.
[1215] mp 178-179.degree. C.
[1216] .sup.1H-NMR (270 MHz, CDCl.sub.3/deuterated methanol=1/9):
.delta. ppm 3.22 (1H, dd, J=8.0, 14.5 Hz), 3.26 (1H, dd, J=5.0,
14.5 Hz), 3.84 (2H, q, J=5.0 Hz), 4.36 (2H, t, J=5.0 Hz), 4.83 (1H,
dd, J=5.0, 8.0 Hz), 6.85 (2H, d, J=8.0 Hz), 6.92 (1H, t, J=7.5 Hz),
7.23 (2H, dd, J=7.5, 8.0 Hz), 7.24 (1H, d, J=6.5 Hz), 7.40 (1H, dd,
J=4.5, 6.5 Hz), 7.58 (1H, dd, J=2.0, 8.5 Hz), 7.84 (1H, d, J=2.0
Hz), 7.91 (1H, t, J=8.5 Hz), 7.92 (1H, t, J=4.5 Hz), 7.96 (2H, d,
J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz), 8.65 (1H, d, J=4.5 Hz).
EXAMPLE 167
Methyl
(S)-2-benzyloxycarbonylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)e-
thoxy]phenyl]propionate (methyl ester of exemplification No. 144-63
compound)
[1217] In a similar manner to that described in Example 73, a
reaction was carried out using methyl
(S)-2-benzyloxycarbonylamino-3-[4-(2-t-butoxycar-
bonylaminoethoxy)phenyl]propionate (368 mg), which is the product
of Reference example 54, 4-pyridine-2-ylbenzoic acid (175 mg),
diethyl cyanophosphonate (0.13 ml) and triethylamine (0.22 ml) and
the reaction mixture was treated to give the title compound (300
mg) as colorless crystals.
[1218] mp 150-151.degree. C.
[1219] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.90-3.12
(2H, m), 3.72 (3H, s), 3.82-3.94 (2H, m), 0.15 (2H, t, J=5.0 Hz),
4.55-4.69 (1H, m), 5.09 (2H, ABq, J=12.5 Hz, .delta.=0.03 ppm),
5.21 (1H, d, J=8.0 Hz), 6.61-6.72 (1H, m), 6.83 (2H, d, J=8.5 Hz),
7.01 (2H, d, J=8.5 Hz), 7.22-7.41 (6H, m), 7.72-7.82 (2H, m), 7.89
(2H, d, J=8.5 Hz), 8.08 (2H, d, J=8.5 Hz). 8.72 (1H, d, J=5.0
Hz).
EXAMPLE 168
(S)-2-benzyloxycarbonylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]p-
henyl]propionic acid (exemplification No. 144-63 compound)
[1220] In a similar manner to that described in Example 2, methyl
(S)-2-benzyloxycarbonylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]-
phenyl]propionate (200 mg), which is the product of Example 167,
was reacted with aqueous sodium hydroxide solution (1N, 0.72 ml)
and the reaction mixture was treated to give the title compound
(144 mg) as a mass of foam.
[1221] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.08 (2H, d,
J=5.0 Hz), 3.68-4.00 (2H, m), 4.08-4.30 (2H, m), 4.55-4.69 (1H, m),
5.11 (2H, s), 5.37 (1H, d, J=8.0 Hz), 6.70-6.90 (3H, m), 6.99 (2H,
d, J=8.5 Hz), 7.20-7.41 (6H, m), 7.70-7.93 (6H, m), 8.70 (1H, d,
J=4.5 Hz).
EXAMPLE 169
Methyl
(S)-2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (methyl ester of exemplification No. 144-13
compound)
[1222] In a similar manner to that described in Reference example
1(d), a reaction was carried out using methyl
(S)-2-benzyloxycarbonylamino-3-[4-[-
2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate (1.53 g)
and palladium on carbon (5%, 150 mg) and the reaction mixture was
treated to give methyl
(S)-2-amino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]pheny-
l]propionate (1.14 g). Propyl bromide (0.24 ml) and potassium
carbonate (387 mg) were added to a solution of the amine derivative
(1.12 g) obtained above in N,N-dimethylformamide (10 ml). The
mixture was stirred at 70.degree. C. for 16 hours. The reaction
mixture was partitioned between ethyl acetate and water and the
ethyl acetate layer was separated and dried over anhydrous
magnesium sulfate and concentrated under reduced pressure. The
residue was purified via chromatography on a silica gel column
using dichloromethane/methanol=19/1 to give the title compound (196
mg) as colorless crystals.
[1223] mp 86-87.degree. C.
[1224] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.5 Hz), 1.39-1.59 (2H, m), 2.39-2.60 (2H, m), 2.90 (2H, d, J=7.0
Hz), 3.48 (1H, t, J=7.0 Hz), 3.64 (3H, s), 3.87-3.95 (2H, m),
4.10-4.20 (2H, m), 6.60-6.71 (1H, m), 6.86 (2H, d, J=8.5 Hz), 7.11
(2H, d, J=8.5 Hz), 7.25-7.30 (1H, m), 7.78-7.80 (2H, m), 7.89 (2H,
d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz), 8.72 (1H, d, J=5.0 Hz).
EXAMPLE 170
(S)-2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propi-
onic acid (exemplification No. 144-13 compound)
[1225] In a similar manner to that described in Example 2, methyl
(S)-2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionate (169 mg), which is the product of Example 169, was reacted
with aqueous sodium hydroxide solution (1N, 0.73 ml) and the
reaction mixture was treated to give the title compound (144 mg) as
colorless crystals.
[1226] mp 242-244.degree. C.
[1227] .sup.1H-NMR of sodium salt (270 MHz, deuterated dimethyl
sulfoxide): .delta. ppm 0.76 (3H, t, J=7.5 Hz), 1.15-1.35 (2H, m),
1.60-1.72 (1H, m), 2.04-2.21 (1H, m), 2.31-2.50 (1H, m), 2.70-2.81
(2H, m), 3.30-3.41 (1H, m), 3.58-3.72 (2H, m), 4.00-4.12 (2H, m),
6.80 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 7.37-7.45 (1H, m),
7.88-8.11 (4H, m), 8.19 (2H, d, J=8.5 Hz), 8.70 (1H, d, J=4.5 Hz),
8.80-8.88 (1H, m).
EXAMPLE 171
Ethyl
2-phenylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate (ethyl ester of exemplification No. 144-68 compound)
[1228] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 3-(4-hydroxyphenyl)-2-(phenylamino-
)propionate, which is the product of Reference example 55(b),
triphenylphosphine and diethyl azodicarboxylate to give the title
compound.
EXAMPLE 172
2-Phenylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 144-68 compound)
[1229] Ethyl
2-phenylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate is hydrolyzed by sodium hydroxide in methanol to
give the title compound.
EXAMPLE 173
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenylaminopropio-
nate (ethyl ester of exemplification No. 144-67 compound)
[1230] In a similar manner to that described in Example 122 , a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl 3-(4-hydroxyphenyl)-2-(phenylamino)propionate, which is the
product of Reference example 55(b) triphenylphosphine and diethyl
azodicarboxylate to give the title compound.
EXAMPLE 174
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenylaminopropionate
(exemplification No. 144-67 compound)
[1231] Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-phenylamin-
opropionate, which is the product of Example 173, is hydrolyzed by
sodium hydroxide in methanol to give the title compound.
EXAMPLE 175
Ethyl
2-ethylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]prop-
ionate hydrochloride (ethyl ester of exemplification No. 144-8
compound)
[1232] (a) Ethyl
2-(N-t-butoxycarbonyl)ethylamino-3-[4-[2-(4-pyridine-2-yl-
benzoylamino)ethoxy]phenyl]propionate
[1233] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 2-(N-t-butoxycarbonyl)ethylamino-3-
-(4-hydroxyphenyl)propionate, which is the product of Reference
example 59(b) triphenylphosphine and diethyl azodicarboxylate to
give the title compound.
[1234] (b) Ethyl
2-ethylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]-
phenyl]propionate hydrochloride (ethyl ester of exemplification No.
144-8 compound)
[1235] Ethyl
2-(N-t-butoxycarbonyl)ethylamino-3-[4-[2-(4-pyridine-2-ylbenz-
oylamino)-ethoxy]phenyl]propionate is treated with a solution of
hydrogen chloride in dioxane (4N) to give the title compound.
EXAMPLE 176
2-Ethylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionate
(exemplification No. 144-8 compound)
[1236] Ethyl
2-ethylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionate hydrochloride, which is the product of Example
175(b), is hydrolyzed by sodium hydroxide in methanol to give the
title compound.
EXAMPLE 177
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-ethylaminopropion-
ate hydrochloride (ethyl ester of exemplification No. 144-7
compound)
[1237] (a) Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-t-b-
utoxycarbonyl)ethylaminopropionate
[1238] In a similar manner to that described in Example 122 , a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl
2-(N-t-butoxycarbonyl)ethylamino-3-(4-hydroxyphenyl)propionate,
which is the product of Reference example 59(b), triphenylphosphine
and diethyl azodicarboxylate to give the title compound.
[1239] (b) Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-ethyla-
minopropionate hydrochloride (ethyl ester of exemplification No.
144-7 compound)
[1240] Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-t-butox-
ycarbonyl)ethylaminopropionate, which is the product of Example
177(a), is treated with a solution of hydrogen chloride in dioxane
(4N) to give the title compound.
EXAMPLE 178
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-ethylaminopropionic
acid (exemplification No. 144-7 compound)
[1241] Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-ethylamino-
propionate hydrochloride, which is the product of Example 177(b),
is hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 179
Ethyl
2-(N-ethyl-N-phenylamino)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethox-
y]phenyl]propionate (ethyl ester of exemplification No. 144-33
compound)
[1242] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 2-(N-ethyl-N-phenylamino)-3-(4-hyd-
roxyphenyl)propionate, which is the product of Reference example
56(b), triphenylphosphine and diethyl azodicarboxylate to give the
title compound.
EXAMPLE 180
2-(N-ethyl-N-phenylamino)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phen-
yl]propionic acid (exemplification No. 144-33 compound)
[1243] Ethyl
2-(N-ethyl-N-phenylamino)-3-[4-[2-(4-pyridine-2-ylbenzoylamin-
o)ethoxy]phenyl]propionate, which is the product in Example 179, is
hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 181
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-ethyl-N-phenyl-
amino)propionate (ethyl ester of exemplification No. 144-32
compound)
[1244] In a similar manner to that described in Example 122, a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl 2-(N-ethyl-N-phenylamino)-3-(4-hydroxyphenyl)propionate,
which is the product of Reference example 56(b), triphenylphosphine
and diethyl azodicarboxylate to give the title compound.
EXAMPLE 182
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-ethyl-N-phenylamino)-
propionic acid (exemplification No. 144-32 compound)
[1245] Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-ethyl-N-
-phenylamino)propionate, which is the product of Example 181, is
hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 183
Ethyl
2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pro-
pionate hydrochloride (ethyl ester of exemplification No. 144-13
compound)
[1246] (a) Ethyl
2-(N-t-butoxycarbonyl)propylamino-3-[4-[2-(4-pyridine-2-y-
lbenzoylamino)ethoxy]phenyl]propionate
[1247] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 2-N-t-butoxycarbonyl)propylamino-3-
-(4-hydroxyphenyl)propionate, which is the product of Reference
example 60(b) triphenylphosphine and diethyl azodicarboxylate to
give the title compound.
[1248] (b) Ethyl
2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy-
]phenyl]propionate hydrochloride (ethyl ester of exemplification
No. 144-13 compound)
[1249] Ethyl
2-(N-t-butoxycarbonyl)propylamino-3-[4-[2-(4-pyridine-2-ylben-
zoylamino)ethoxy]-phenyl]propionate, which is the product of
Example 183(a), is treated with a solution of hydrogen chloride in
dioxane (4N) to give the title compound.
EXAMPLE 184
2-Propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propionic
acid (exemplification No. 144-13 compound)
[1250] Ethyl
2-propylamino-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate hydrochloride, which is the product of Example
183(b) is hydrolyzed by sodium hydroxide in methanol to give the
title compound.
EXAMPLE 185
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-propylaminopropio-
nate hydrochloride (ethyl ester of exemplification No. 144-12
compound)
[1251] (a) Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N-t-b-
utoxycarbonyl)propylaminopropionate
[1252] In a similar manner to that described in Example 122 a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl
2-(N-t-butoxycarbonyl)propylamino-3-(4-hydroxyphenyl)propionate,
which is the product of Reference example 60(b), triphenylphosphine
and diethyl azodicarboxylate to give the title compound.
[1253] (b) Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-propyl-
aminopropionate hydrochloride (ethyl ester of exemplification No.
144-12 compound)
[1254] Ethyl
2-(N-t-butoxycarbonyl)propylamino-3-[4-[2-(4-phenylbenzoylami-
no)ethoxy]phenyl]propionate, which is the product of Example
185(a), is treated with a solution of hydrogen chloride in dioxane
(4N) to give the title compound.
EXAMPLE 186
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-propylaminopropionic
acid (exemplification No. 144-12 compound)
[1255] Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-propylamin-
opropionate hydrochloride, which is the product of Example 185(b),
is hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 187
Ethyl
2-(N,N-diethylamino)-3-[4-[2-(4-pyridine-2-benzoylamino)ethoxy]pheny-
l]propionate (ethyl ester of exemplification No. 144-28
compound)
[1256] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 2-(N,N-diethylamino)-3-(4-hydroxyp-
henyl)propionate, which is the product of Reference example 58,
triphenylphosphine and diethyl azodicarboxylate to give the title
compound.
EXAMPLE 188
2-(N,N-Diethylamino)-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]pr-
opionic acid (exemplification No. 144-28 compound)
[1257] Ethyl
2-(N,N-diethylamino)-3-[4-[2-(4-pyridine-2-benzoylamino)ethox-
y]phenyl]propionate, which is the product Example 187. is
hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 189
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N,N-diethylamino-
)propionate (ethyl ester of exemplification No. 144-27
compound)
[1258] In a similar manner to that described in Example 122 , a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl 2-(N,N-diethylamino)-3-(4-hydroxyphenyl)propionate, which is
the product of Reference example 58, triphenylphosphine and diethyl
azodicarboxylate to give the title compound.
EXAMPLE 190
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(N,N-diethylamino)propi-
onic acid (exemplification No. 144-27 compound)
[1259] Ethyl
2-(N,N-diethylamino)-3-[4-[2-(4-phenylbenzoylamino)ethoxy]phe-
nyl]propionate, which is the product of Example 189, is hydrolyzed
by sodium hydroxide in methanol to give the title compound.
EXAMPLE 191
Ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyrrole-1-yl)-
propionate (ethyl ester of exemplification No. 144-38 compound)
[1260] In a similar manner to that described in Example 122 , a
reaction is carried out using
2-(4-pyridine-2-ylbenzoylamino)ethanol, which is the product of
Reference example 61, ethyl 3-(4-hydroxyphenyl)-2-(pyrrole-1-y-
l)propionate, which is the product of Reference example 57(b),
triphenylphosphine and diethyl azodicarboxylate to give the title
compound.
EXAMPLE 192
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyrrole-1-yl)propio-
nic acid (exemplification No. 144-38 compound)
[1261] Ethyl
3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]-2-(pyrrol-
e-1-yl)propionate, which is the product of Example 191. is
hydrolyzed by sodium hydroxide in methanol to give the title
compound.
EXAMPLE 193
Ethyl
3-[4-[2-(biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(pyrrole-1-yl)pro-
pionate (ethyl ester of exemplification No. 144-37 compound)
[1262] In a similar manner to that described in Example 122 , a
reaction is carried out using 2-(biphenyl-4-carbonylamino)ethanol,
ethyl 3-(4-hydroxyphenyl)-2-(pyrrole-1-yl)propionate, which is the
product of Reference example 57(b), triphenylphosphine and diethyl
azodicarboxylate to give the title compound.
EXAMPLE 194
3-[4-[2-(Biphenyl-4-carbonylamino)ethoxy]phenyl]-2-(pyrrole-1-yl)propionic
acid (exemplification No. 144-37 compound)
[1263] Ethyl
3-[4-[2-(4-phenylbenzoylamino)ethoxy]phenyl]-2-(pyrrole-1-yl)-
propionate, which is the product of Example 193, is hydrolyzed by
sodium hydroxide in methanol to give the title compound.
Reference Example 1
Ethyl 2-ethoxy-3-[4-(2-phthaliminoethoxy)phenyl]propionate
[1264] (a) N-[2-(methanesulfonyloxy)ethyl]phthalimide
[1265] After methanesulfonyl chloride (12.7 g) was added to a
solution of N-(2-hydroxyethyl)phthalimide (19.1 g) in anhydrous
dichloromethane (200 ml), triethylamine (20 ml) was added dropwise
to the mixture in an ice bath. The mixture was stirred at ambient
temperature for 4 hours. At the end of this time the reaction
mixture was concentrated under reduced pressure. The residual solid
was washed with ethyl acetate and water and then recrystallized
from ethyl acetate to afford the desired compound (18.2 g).
[1266] mp 138-139.degree. C.
[1267] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.02 (3H, s),
4.05 (2H, t, J=5.5 Hz), 4.49 (2H, t, J=5.5 Hz), 7.70-7.80 (2H, m),
7.83-7.93 (2H, m).
[1268] (b) Ethyl 3-(4-benzyloxyphenyl)lactate
[1269] Benzyl bromide (21.9 g) and potassium carbonate (35.3 g)
were added to a solution of ethyl 3-(4-hydroxyphenyl)lactate (22.4
g) in dimethylformamide (220 ml). The mixture was stirred at
50.degree. C. for 2 hours. The reaction mixture was partitioned
between ethyl acetate and water. The ethyl acetate layer was
separated and dried over magnesium sulfate and then concentrated
under reduced pressure. The residue was purified via chromatography
silica gel column using hexane/ethyl acetate=7/3 as the eluant to
give the desired compound (31.0 g) as a pale yellow oil.
[1270] (c) Ethyl 3-(4-benzyloxyphenyl)-2-ethoxypropionate
[1271] Sodium hydride (55% suspension in oil, 1.65 g) was added to
a solution ethyl 3-(4-benzyloxyphenyl)lactate (10.30 g), which is
the product of Reference example 1(b), in a mixture of
N,N-dimethylacetamide (50 ml) and toluene (50 ml). The mixture was
stirred at 40.degree. C. for 30 minutes. To the reaction mixture
were added ethyl iodide (3.3 ml) and toluene (5 ml). This mixture
was stirred at 40.degree. C. for 2 hours. At the end of this time
the reaction mixture was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and dried over
anhydrous magnesium sulfate and evaporated under reduced pressure.
The residue was purified via chromatography on a silica gel column
using hexane/ethyl acetate=5/1 as the eluant to give the desired
compound (5.50 g) as a syrup.
[1272] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.11-1.26
(6H, m), 2.95 (2H, d, J=6.5 Hz), 3.36 (1H, quintuplet, J=7.0 Hz),
3.60 (1H, quintuplet, J=7.0 Hz), 3.97 (1H, t, J=6.5 Hz), 4.15 (2H,
q, J=7.0 Hz), 5.05 (2H, s), 6.89 (2H, d, J=8.5 Hz), 7.16 (2H, d,
J=8.5 Hz) 7.30-7.48 (5H, m).
[1273] (d) Ethyl 2-ethoxy-3-hydroxyphenylpropionate
[1274] Palladium on carbon (5%, 0.70 g) was added to a solution of
ethyl 3-(4-benzyloxyphenyl)-2-ethoxypropionate (5.50 g), which is
the product of Reference example 1(c), in ethanol (60 ml). The
mixture was stirred under an atmosphere of hydrogen at 40.degree.
C. for 2 hours. At the end of this time the catalyst was removed by
filtration and the filtrate was concentrated under reduced
pressure. The residue was partitioned between ethyl acetate and
water and the the layers were separated. The ethyl acetate layer
was dried over anhydrous magnesium sulfate and then concentrated
under reduced pressure to afford the desired product (3.80 g) as a
syrup.
[1275] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.12-1.28
(6H, m), 2.95 (2H, d, J=6.5 Hz), 3.37 (1H, quintuplet, J=7.0 Hz),
3.60 (1H, quintuplet, J=7.0 Hz), 3.99 (1H, t, J=6.5 Hz), 4.19 (2H,
q, J=7.0 Hz), 5.38 (1H, s), 6.73 (2H, d, J=8.5 Hz), 7.10 (2H, d,
J=8.5 Hz).
[1276] (e) Ethyl
2-ethoxy-3-[4-(2-phthaliminoethoxy)phenyl]propionate
[1277] Sodium hydride (55% suspension in oil, 200 mg) was added to
a solution of ethyl 2-ethoxy-3-hydroxyphenylpropionate (1.00 g),
which is the product of Reference example 1(d), in a mixture of
dimethylacetamide (10 ml) and toluene (10 ml). The mixture was
stirred at ambient temperature for 20 minutes. To the reaction
mixture N-[2-(methanesulfonyloxy)ethyl]phthalimide (1.50 g), which
is the product of Reference example 1(a), was added and the mixture
was stirred at 70.degree. C. for 2.5 hours and then at 60.degree.
C. for 24 hours. At the end of this time the reaction mixture was
partitioned between ethyl acetate and water. The ethyl acetate was
separated and dried over anhydrous magnesium sulfate and evaporated
under reduced pressure. The residue was purified via chromatography
on a silica gel column using benzene/ethyl acetate=8/1 as the
eluant to afford the title compound (0.31 g) as a syrup.
[1278] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.09-1.28
(6H, m), 2.92 (2H, d, J=6.5 Hz), 3.37 (1H, quintuplet, J=7.0 Hz),
3.58 (1H, quintuplet, J=7.0 Hz), 3.93 (1H, t, J=6.5 Hz), 4.06-4.25
(6H, m), 6.79 (2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz), 7.68-7.91
(4H, m).
Reference Example 2
Ethyl
2-(3-phenylpropyl)-3-[4-(2-phthaliminoethoxy)phenyl]propionate
[1279] (a) Diethyl
2-(4-benzyloxybenzyl)-2-(3-phenylpropyl)malonate
[1280] Sodium hydride (55% suspension in oil, 0.48 g) was added to
a solution of diethyl 2-(3-phenylpropyl)malonate (2.78 g) in a
mixture of N,N-dimethylacetamide (10 ml) and toluene (20 ml). The
mixture was stirred at ambient temperature for 30 minutes. To the
reaction mixture 4-benzyloxybenzyl chloride (2.45 g) was added and
the mixture was stirred at ambient temperature for 30 minutes and
then at 60.degree. C. for 30 minutes. At the end of this time the
reaction mixture was partitioned between ethyl acetate and water.
The ethyl acetate layer was separated and dried over anhydrous
magnesium sulfate and concentrated. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=9/1 as the eluant to afford the desired compound (3.91 g)
as a syrup.
[1281] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, t,
J=7.0 Hz), 1.57-1.66 (2H, m), 1.76-1.85 (2H, m), 2.61 (2H, t, J=6.5
Hz), 3.14 (2H, s), 4.15 (4H, dq, J=1.5, 7.0 Hz), 5.01 (2H, s), 6.79
(2H, d, J=8.5 Hz), 6.89 (2H, d, J=8.5 Hz), 7.15-7.44 (10H, m).
[1282] (b) Ethyl 2-(4-benzyloxybenzyl)-5-phenylvalerate
[1283] Potassium hydroxide (2.00 g) was added to a solution of
diethyl 2-(4-benzyloxybenzyl)-2-(3-phenylpropyl)malonate (3.91 g)
in a mixture of 2-methoxyethanol (30 ml) and water (3 ml). The
mixture was stirred at 130.degree. C. in an oil bath for 1.5 hours.
At the end of this time the reaction mixture was partitioned
between ethyl acetate and water and the mixture was acidified with
aqueous hydrogen chloride solution (6N). The ethyl acetate layer
was separated and washed with aqueous sodium chloride solution and
dried over anhydrous magnesium sulfate and concentrated. A solution
of the residual syrup in xylene (20 ml) was stirred for 1 hour and
then concentrated. Concentrated sulfuric acid (1 ml) was added to a
solution of the syrup residue of
2-(4-benzyloxybenzyl)-5-phenylvaleric acid in ethanol (40 ml). The
mixture was stirred at 80.degree. C. for 3 hours and allowed to
stand at ambient temperature for 16 hours. At the end of this time
the reaction mixture was concentrated and the residue was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and dried over anhydrous magnesium sulfate and
concentrated to dryness to afford the desired compound (3.32 g) as
a syrup.
[1284] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.50-1.80 (4H, m), 2.53-2.71 (4H, m), 2.82-2.90 (1H, m),
4.04 (2H, q, J=7.0 Hz), 5.04 (2H, s), 6.87 (2H, d, J=8.5 Hz), 7.05
(2H, d, J=8.5 Hz), 7.10-7.44 (10H, m).
[1285] (c) Ethyl 2-(4-hydroxybenzyl)-5-phenylvalerate
[1286] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
2-(4-benzyloxybenzyl)-5-phenylvalera- te (3.32 g) and palladium on
carbon (5%, 0.40 g) and the reaction mixture was treated to afford
the desired compound (2.56 g) as a syrup.
[1287] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.14 (3H, t,
J=7.0 Hz), 1.50-1.75 (4H, m), 2.53-2.71 (4H, m), 2.78-2.87 (1H, m),
4.05 (2H, q, J=7.0 Hz), 6.70 (2H, d, J=8.5 Hz), 6.98 (2H, d, J=8.5
Hz), 7.12-7.29 (5H, m).
[1288] (d) Ethyl
2-(3-phenylpropyl)-3-[4-(2-phthaliminoethoxy)phenyl]propi-
onate
[1289] In a similar manner to that described in Reference example
1(e), a reaction was carried out using ethyl
2-(4-hydroxybenzyl)-5-phenylvalerate (1.42 g), which is the product
of Reference example 2(c), sodium hydride (55% suspension in oil,
228 mg) and N-[2-(methanesulfonyloxy)ethyl]phthal- imide (1.25 g),
which is the product of Reference example 1(a) and the reaction
mixture was treated to afford the desired compound (1.34 g) as a
syrup.
[1290] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.12 (3H, t,
J=7.0 Hz), 1.46-1.70 (4H, m), 2.50-2.70 (4H, m), 2.76-2.89 (1H, m),
4.02 (2H, q, J=7.0 Hz), 4.10 (2H, t, J=5.5 Hz), 4.19 (2H, t, J=5.5
Hz), 6.77 (2H, d, J=8.5 Hz), 7.00 (2H, d, J=8.5 Hz), 7.10-7.20 (3H,
in), 7.21-7.29 (2H, m), 7.69-7.76 (2H, m), 7.82-7.89 (2H, m).
Reference Example 3
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-(2-phenoxyethyl)propionate
[1291] (a) Diethyl 2-(4-methoxybenzylidene)malonate
[1292] Piperidine (1.5 ml) and diethyl malonate (14.9 ml) were
added to a solution of 4-methoxymethoxybenzaldehyde (16.2 g) in
ethanol (160 ml). The mixture was heated at reflux for 7 hours. At
the end of this time ethyl acetate was added to the reaction
mixture and the ethyl acetate was washed with aqueous hydrogen
chloride solution (0.8N) and saturated aqueous sodium
hydrogencarbonate solution and saturated aqueous sodium chloride
and dried over anhydrous magnesium sulfate and then concentrated.
The residue was purified via chromatography on a silica gel column
using hexane/ethyl acetate=9/1-3/1 as the eluant to afford the
desired compound (5.00 g) as a syrup.
[1293] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.33 (6H, t,
J=7.0 Hz), 3.48 (3H, s), 4.29 (2H, q, J=7.0 Hz), 4.36 (2H, q, J=7.0
Hz), 5.20 (2H, s), 7.03 (2H, d, J=9.0 Hz), 7.42 (2H, d, J=9.0 Hz),
7.67 (1H, s).
[1294] (b) Diethyl 2-(4-methoxymethoxybenzyl)malonate
[1295] In a similar manner to that described in Reference example
1(d), a reaction was carried out using diethyl
2-(4-methoxymethoxybenzylidene)mal- onate (4.98 g) and palladium on
carbon (5%, 0.50 g) and the reaction mixture was treated to afford
the desired compound (5.00 g) as a syrup.
[1296] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.24 (6H, t,
J=7.0 Hz), 3.18 (2H, d, J=8.0 Hz), 3.49 (3H, s), 3.62 (1H, t, J=8.0
Hz), 4.18 (4H, q, J=7.0 Hz), 5.17 (2H, s), 6.97 (2H, d, J=8.5 Hz),
7.15 (2H, d, J=8.5 Hz).
[1297] (c) Diethyl
2-(4-methoxymethoxybenzyl)-2-(2-phenoxyethyl)malonate
[1298] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl
2-(4-methoxymethoxybenzyl)malonate (1.58 g), which is the product
of Reference example 3(b), sodium hydride (55% suspension in oil,
0.24 g) and 2-phenoxyethyl bromide (1.23 g) and the reaction
mixture was treated to afford the desired compound (1.72 g) as a
syrup.
[1299] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (6H, t,
J=7.5 Hz), 2.30 (2H, t, J=6.5 Hz), 3.30 (2H, s), 3.47 (3H, s), 4.08
(2H, t, J=6.5 Hz), 4.19 (4H, q, J=7.5 Hz), 5.14 (2H, s), 6.84-6.96
(5H, m), 7.05 (2H, d, J=9.0 Hz), 7.16-7.30 (2H, m).
[1300] (d) Ethyl 2-(4-hydroxybenzyl)-4-phenoxybutyrate
[1301] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-(4-methoxymethoxybenzyl)-2-(2-ph- enoxyethyl)malonate (1.71 g)
and potassium hydroxide and the reaction mixture was treated to
afford the desired compound (1.25 g) as a syrup.
[1302] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.90-2.20 (2H, m), 2.74-2.98 (3H, m), 3.90-4.14 (4H, m),
4.71 (1H, s), 6.74 (2H, d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz), 6.93
(1H, t, J=7.5 Hz), 7.05 (2H, d, J=8.5 Hz), 7.22-7.30 (2H, m).
[1303] (e) Ethyl
2-(2-phenoxyethyl)-3-[4-[2-(tetrahydropyran-2-yl-oxy)etho-
xy]-phenyl]propionate
[1304] 2-(2-bromoethoxy)tetrahydropyran (1.24 g) and potassium
carbonate (1.09 g) were added to a solution of ethyl
2-(4-hydroxybenzyl)-4-phenoxyb- utyrate (620 mg), which is the
product of Reference example 3(d), in 2-butanone (8 ml). The
mixture was stirred at 100.degree. C. for 5 hours. To the reaction
mixture dimethylacetamide (10 ml) was added and the mixture was
stirred at 100.degree. C. for 1.5 hours. At the end of this time
the reaction mixture was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and washed with
saturated aqueous sodium chloride solution and dried over anhydrous
magnesium sulfate and then concentrated. The residue was purified
via chromatography on a silica gel column using hexane/ethyl
acetate=4/1 as the eluant to afford the desired compound (738 mg)
as a syrup.
[1305] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.50-2.10 (8H, m), 2.73-2.98 (3H, m), 3.48-3.58 (1H, m),
3.77-4.17 (9H, m), 4.71 (1H, t, J=3.5 Hz), 6.82-6.87 (4H, m), 6.93
(1H, t, J=7.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.23-7.29 (2H, m).
[1306] (f) Ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-(2-phenoxyethyl)propionat- e
[1307] p-Toluenesulfonic acid monohydrate (0.40) was added to a
solution of ethyl
2-(2-phenoxyethyl)-3-[4-[2-(tetrahydropyran-2-yloxy)ethoxy]pheny-
l]propionate (738 mg), which is the product of Reference example
3(e), in ethanol (10 ml). The mixture was stirred at ambient
temperature for 2 hours. At the end of this time the reaction
mixture was concentrated. The residue was partitioned between ethyl
acetate and saturated aqueous sodium hydrogencarbonate solution.
The ethyl acetate layer was separated and dried over anhydrous
magnesium sulfate and then concentrated. The residue was purified
via chromatography on a silica gel column using hexane/ethyl
acetate=7/3-3/2 as the eluant to afford the desired compound (503
mg) as a syrup.
[1308] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.90-2.10 (3H, m), 2.75-3.00 (3H, m), 3.92-4.11 (8H, m),
6.82-6.87 (4H, m), 6.93 (1H, t, J=7.5 Hz), 7.10 (2H, d, J=8.5 Hz),
7.23-7.29 (2H, m).
[1309] (g) Ethyl
3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-(2-phenoxyethy-
l)propionate Triethylamine (0.29 ml) and methanesulfonyl chloride
(0.12 ml) were added to a solution of ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-(2-- phenoxyethyl)propionate (503
mg), which is the product of Reference example 3(f), in anhydrous
dichloromethane (10 ml). The reaction mixture was stirred at
ambient temperature for 2 hours. At the end of this time the
reaction mixture was concentrated. The residue was partitioned
between ethyl acetate and water. The ethyl acetate layer was
separated and dried over anhydrous magnesium sulfate and then
concentrated. The residue was purified via chromatography on silica
gel column using hexane/ethyl acetate=2/1-3/2 as the eluant to
afford the desired compound (632 mg) as a syrup.
[1310] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.90-2.20 (2H, m), 2.75-3.00 (3H, m), 3.09 (3H, s),
3.89-4.02 (2H, m), 4.07 (2H, q, J=7.0 Hz), 4.20-4.23 (2H, m),
4.54-4.58 (2H, m), 6.80-6.87 (4H, m), 6.93 (1H, t, J=7.5 Hz), 7.11
(2H, d, J=8.5 Hz), 7.23-7.30 (2H, m).
[1311] (h) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(2-phenoxyethyl)propionate
[1312] Sodium azide (0.29 g) was added to a solution of ethyl
3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-(2-phenoxyethyl)propionate,
which is the product of Reference example 3(g), in
dimethylformamide (8 ml). The mixture was stirred at 70.degree. C.
for 2 hours. At the end of this time the reaction mixture was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and dried over anhydrous magnesium sulfate and
then concentrated to afford the desired compound (546 mg) as a
syrup.
[1313] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.90-2.20 (2H, m), 2.75-3.00 (3H, m), 3.58 (2H, t, J=5.0
Hz), 3.89-4.14 (6H, m), 6.81-6.87 (4H, m), 6.93 (1H, t, J=7.5 Hz),
7.11 (2H, d, J=8.5 Hz), 7.22-7.30 (2H, m).
[1314] (i) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(phenoxyethyl)propionate
[1315] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(2-phe- noxyethyl)propionate (538 mg)
and palladium on carbon (5%, 500 mg) and the reaction mixture was
treated to afford the title compound (476 mg) as a syrup.
[1316] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13 (3H, t,
J=7.0 Hz), 1.66 (2H, brs), 1.90-2.21 (2H, m), 2.75-3.07 (3H, m),
3.08 (2H, t, J=5.0 Hz), 3.90-4.12 (6H, m), 6.82-6.88 (4H, m), 6.93
(1H, t, J=7.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.23-7.30 (2H, m).
Reference Example 4
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate
[1317] (a) Diethyl 2-(4-benzyloxybenzyl)-2-phenoxymalonate
[1318] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl 2-phenoxymalonate
(2.81 g), 4-benzyloxybenzyl chloride (2.59 g) and sodium hydride
(55% suspension in oil, 530 mg) and the reaction mixture was
treated to afford the desired compound (3.10 g) as a syrup.
[1319] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.12 (6H, t,
J=7.0 Hz), 3.57 (2H, s), 4.15 (4H, q, J=7.0 Hz), 5.02 (2H, s),
6.84-7.14 (6H, m), 7.22-7.41 (8H, m).
[1320] (b) Ethyl 3-(4-benzyloxyphenyl)-2-phenoxypropionate
[1321] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-(4-benzyloxbenzyl)-2-phenoxymalo- nate (3.10 g) and potassium
hydroxide (2.10 g) and the reaction mixture was treated to afford,
via a syrup of 3-(4-benzyloxyphenyl)-2-phenoxyprop- ionic acid, the
desired compound (2.10 g) as a syrup.
[1322] .sup.1H-NMR (270 MHz CDCl.sub.3): .delta. ppm 1.18 (3H, t,
J=7.0 Hz), 3.11-3.20 (2H, m), 4.16 (2H, q, J=7.0 Hz), 4.74 (1H, dd,
J=5.5, 6.5 Hz), 5.04 (2H, s), 6.84 (2H, d, J=8.0 Hz), 6.91 (2H, d,
J=8.5 Hz), 6.92-6.97 (1H, m), 7.05-7.09 (1H, m), 7.22 (2H, d, J=8.5
Hz), 7.20-7.43 (6H, m).
[1323] (c) Ethyl 3-(4-hydroxyphenyl)-2-phenoxypropionate
[1324] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-phenoxypropi- onate (2.10 g), which is the
product of Reference example 4(b) and palladium on carbon (5%, 0.32
g) and the reaction mixture was treated to afford the desired
compound (1.01 g) as a syrup.
[1325] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.10-3.24 (2H, m), 4.17 (2H, q, J=7.0 Hz), 4.74 (1H, dd,
J=6.0, 7.0 Hz), 5.00 (1H, s), 6.74 (2H, d, J=8.5 Hz), 6.84 (2H, d,
J=8.0 Hz), 6.95 (1H, t, J=7.5 Hz), 7.16 (2H, d, J=8.5 Hz),
7.21-7.26 (2H, m).
[1326] (d) Ethyl
2-phenoxy-3-[4-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl]-
propionate
[1327] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-phenoxypropion- ate (3.33 g), which is the
product of Reference example 4(c), 2-(2-bromoethoxy)tetrahydropyran
(7.27 g) and potassium carbonate (6.41 g) in dimethylacetamide and
the reaction mixture was treated to afford the desired compound
(4.53 g) as a syrup.
[1328] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 1.50-1.88 (6H, m), 3.16-3.20 (2H, m), 3.48-3.56 (1H, m),
3.76-3.93 (2H, m), 4.00-4.21 (5H, m), 4.69-4.76 (2H, m), 6.83 (2H,
d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 6.94 (1H, t, J=7.0 Hz),
7.18-7.26 (4H, m).
[1329] (e) Ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-phenoxypropionate
[1330] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-phenoxy-3-[4-[2-(tetrahydropyran-2-
-yloxy)ethoxy]phenyl]propionate (4.53 g), which is the product of
Reference example 4(d), and p-toluene-sulfonic acid monohydrate
(2.70 g) and the reaction mixture was treated to afford the desired
compound (3.28 g) as a syrup.
[1331] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 1.98-2.02 (1H, brs), 3.14-3.20 (2H, m), 3.90-4.00 (2H,
m), 4.06 (2H, t, J=4.5 Hz), 4.17 (2H, q, J=7.0 Hz), 4.74 (1H, dd,
J=6.0, 7.5 Hz), 6.82-6.88 (4H, m), 6.95 (1H, t, J=7.0 Hz),
7.21-7.26 (4H, m).
[1332] (f) Ethyl
3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-phenoxypropion- ate
[1333] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-phen- oxypropionate (3.27 g), which
is the product of Reference example 4(e), triethylamine (2.07 ml)
and methanesulfonyl chloride (0.84 ml) and the reaction mixture was
treated to afford the desired compound (4.20 g) as a syrup.
[1334] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.07 (3H, s), 3.19 (2H, d, J=7.0 Hz), 4.14-4.25 (4H, m),
4.56 (2H, t, J=4.5 Hz), 4.74 (1H, t, J=7.0 Hz), 6.84 (4H, d, J=8.5
Hz), 6.95 (1H, t, J=7.0 Hz), 7.20-7.29 (4H, m).
[1335] (g) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-phenoxypropionate
[1336] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
3-[4-(2-methanesulfonyloxyethoxy)phe- nyl]-2-phenoxypropionate
(4.00 g), which is the product of Reference example 4(f), and
sodium azide (1.93 g) and the reaction mixture was treated to
afford the desired compound (3.40 g) as a syrup.
[1337] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.14-3.22 (2H, m), 3.58 (2H, t, J=5.0 Hz), 4.13 (2H, t,
J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.74 (1H, dd, J=6.0, 7.5 Hz),
6.82-6.97 (5H, m), 7.21-7.29 (4H, m).
[1338] (h) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate
[1339] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-phenox- ypropionate (3.40 g), which
is the product of Reference example 4(g), and palladium on carbon
(5% 350 mg) and the reaction mixture was treated to afford the
title compound (3.10 g) as a syrup.
[1340] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.07 (2H, t, J=5.0 Hz), 3.14-3.20 (2H, m), 3.90-4.15
(2H, m), 4.17 (2H, q, J=7.0 Hz), 4.74 (1H, dd, J=6.0, 7.0 Hz), 6.84
(4H, d, J=8.5 Hz), 6.94 (1H, t, J=7.5 Hz), 7.19-7.30 (4H, m).
Reference Example 5
Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy)propionate
[1341] (a) Diethyl 2-(4-isopropylphenoxy)malonate
[1342] Sodium hydride (55% suspension in oil, 5.22 g) was added to
a solution of 4-isopropylphenol (15.0 g) in a mixture of
dimethylformamide (63 ml) and toluene (75 ml). The mixture was
stirred at ambient temperature for 1 hour. To the reaction mixture,
diethyl 2-chloromalonate (18.5 g) was added. The mixture was
stirred at 60.degree. C. for 2.5 hours. At the end of this time
ethyl acetate was added to the reaction mixture. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
chloride solution and dried over anhydrous magnesium sulfate and
then concentrated. The residue was purified via chromatography on a
silica gel column using hexane/ethyl acetate=4/1 as the eluant to
afford the desired compound (21.5 g) as a syrup.
[1343] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=7.0 Hz), 2.81-2.95 (1H, m), 3.85 (6H, s), 5.21 (1H, s), 6.88 (2H,
d, J=8.5 Hz), 7.15 (2H, d, J=8.5 Hz).
[1344] (b) Diethyl
2-(4-benzyloxybenzyl)-2-(4-isopropylphenoxy)malonate
[1345] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl
2-(4-isopropylphenoxy)malonate (21.5 g), which is the product of
Reference example 5(a), 4-benzyloxybenzyl chloride (19.7 g) and
sodium hydride (55% suspension in oil, 3.53 g) and the reaction
mixture was treated to afford the desired compound (32.3 g) as a
syrup.
[1346] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=6.5 Hz), 2.79-2.92 (1H, m), 3.55 (2H, s), 3.68 (6H, s), 5.02 (2H,
s), 6.86 (4H, d, J=8.5 Hz), 7.09 (4H, d, J=8.5 Hz), 7.30-7.43 (5H,
m).
[1347] (c) Diethyl
2-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)malonate
[1348] In a similar manner to that described in Reference example
1(d), a reaction was carried out using diethyl
2-(4-benzyloxybenzyl)-2-(4-isoprop- ylphenoxy)malonate (32.3 g),
which is the product of Reference example 5(b), and palladium on
carbon (5%, 2.00 g) and the reaction mixture was treated to afford
the desired compound (25.2 g) as a syrup.
[1349] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=7.0 Hz), 2.75-2.95 (1H, m), 3.54 (2H, s), 3.68 (6H, s), 4.93 (1H,
brs), 6.69 (2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 7.04 (2H, d,
J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz).
[1350] (d) Ethyl
3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propionate
[1351] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-(4-hydroxyphenyl)-2-(4-isopropyl- phenoxy)malonate (25.2 g),
which is the product of Reference example 5(c), and potassium
hydroxide (20.0 g) and the reaction mixture was treated to afford,
via crystals of 3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propion-
ic acid, the desired compound (19.8 g) as a syrup.
[1352] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.13-1.22
(9H, m), 2.75-2.88 (1H, m), 3.11-3.18 (2H, m), 4.17 (2H, q, J=7.5
Hz), 4.69 (1H, dd, J=5.5, 7.5 Hz), 4.77 (1H, brs), 6.76 (4H, d,
J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.17 (2H, d, J=8.5 Hz).
[1353] (e) Ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(tetrahydropyran-2-yloxy)e-
thoxy]phenyl]propionate
[1354] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-(4-isopropylph- enoxy)propionate (14.8 g),
which is the product of Reference example 5(d),
2-(2-bromoethoxy)tetrahydropyran (28.2 g) and potassium carbonate
(24.9 g) in dimethylformamide and the reaction mixture was treated
to afford the desired compound (20.6 g) as a syrup.
[1355] (f) Ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-(4-isopropylphenoxy)propi-
onate
[1356] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)-3-[4-[2-(tetr-
ahydropyran-2-yloxy)ethoxy]phenyl]propionate (20.6 g), which is the
product of Reference example 5(e), and p-toluenesulfonic acid
monohydrate (7.85 g) and the reaction mixture was treated to afford
the desired compound (16.2 g) as a syrup.
[1357] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.15-1.22
(9H, m), 2.75-3.00 (1H, m), 3.12-3.20 (2H, m), 3.90-3.99 (2H, m),
4.06 (2H, t, J=4.5 Hz), 4.17 (2H, q, J=7.5 Hz), 4.69 (1H, dd,
J=5.5, 7.5 Hz), 6.76 (2H, d, J=8.5 Hz), 6.84 (2H, d, J=8.5 Hz),
7.08 (2H, d, J=8.5 Hz), 7.22 (2H. d, J=8.5 Hz).
[1358] (g) Ethyl
2-(4-isopropylphenoxy)-3-[4-(2-methanesulfonyloxyethoxy)p-
henyl]propionate
[1359] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-(4-i- sopropylphenoxy)propionate
(16.2 g), which is the product of Reference example 5(f),
triethylamine (12.1 ml) and methanesulfonyl chloride (5.05 ml) and
the reaction mixture was treated to afford the desired compound
(19.6 g) as a syrup.
[1360] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.16-1.23
(9H, m), 2.72-2.90 (1H, m), 3.07 (3H, s), 3.12-3.19 (2H, m),
4.10-4.23 (4H, m), 4.51-4.58 (2H, m), 4.69 (1H, dd, J=5.5, 7.5 Hz),
6.76 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5
Hz), 7.23 (2H, d, J=8.5 Hz).
[1361] (h) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-isopropylphenoxy)propion- ate
[1362] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)-3-[4-(2-metha-
nesulfonyloxyethoxy)phenyl]propionate (19.6 g), which is the
product of Reference example 5(g), and sodium azide (7.06 g), and
the reaction mixture was treated to afford the desired compound
(15.8 g) as a syrup.
[1363] (i) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy)propion- ate
[1364] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-iso- propylphenoxy)propionate
(15.8 g), which is the product of Reference example 5(h), and
palladium on carbon (5%, 1.60 g) and the reaction mixture was
treated to afford the title compound (13.5 g) as a syrup.
Reference Example 6
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate
[1365] (a) Diethyl 2-(4-benzyloxybenzyl)-2-butylmalonate
[1366] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl 2-butylmalonate
(2.16 g), 4-benzyloxybenzyl chloride (2.44 g) and sodium hydride
(55% suspension in oil, 480 mg) and the reaction mixture was
treated to afford the desired compound (3.67 g) as crystals.
[1367] mp 73.degree. C.
[1368] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.91 (3H, t,
J=7.0 Hz), 1.24 (6H, t, J=7.0 Hz), 1.20-1.38 (4H, m), 1.74-1.80
(2H, m), 3.18 (2H, s), 4.11-4.23 (4H, m), 5.02 (2H, s), 6.86 (2H,
d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz), 7.31-7.44 (5H, m).
[1369] (b) Ethyl 2-(4-benzyloxybenzyl)caproate
[1370] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-(4-benzyloxbenzyl)-2-butylmalona- te (3.60 g), which is the
product of Reference example 6(a), and potassium hydroxide (2.00 g)
and the reaction mixture was treated to afford, via crystals of
2-(4-benzyloxybenzyl)-2-caproic acid, the desired compound (2.71 g)
as a syrup.
[1371] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.14 (3H, t, J=7.0 Hz), 1.20-1.70 (6H, m), 2.51-2.72
(2H, m), 2.85 (1H, dd, J=8.5, 13.5 Hz), 4.05 (2H, q, J=7.0 Hz),
5.03 (2H, s), 6.88 (2H, d, J=8. 5Hz), 7.07 (2H, d, J=8.5 Hz),
7.31-7.45 (5H, m).
[1372] (c) Ethyl 2-(4-hydroxybenzyl)caproate
[1373] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
2-(4-benzyloxybenzyl)caproate (2.71 g), which is the product of
Reference example 6(b), and palladium on carbon (5%, 0.40 g) and
the reaction mixture was treated to afford the desired compound
(1.90 g) as a syrup.
[1374] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.20-1.35 (4H, m), 1.40-1.70
(2H, m), 2.53-2.72 (2H, m), 2.84 (1H, dd, J=8.5, 13.5 Hz), 4.06
(2H, q, J=7 Hz), 4.93 (1H, s), 6.72 (2H, d, J=8.5 Hz), 7.02 (2H, d,
J=8.5 Hz).
[1375] (d) Ethyl
2-butyl-3-[4-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl]pr-
opionate
[1376] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
2-(4-hydroxybenzyl)caproate (2.40 g), which is the product of
Reference example 6(c), 2-(2-bromoethoxy)tetrahydropyran (1.63 g)
and potassium carbonate (3.23 g) in dimethylacetamide and the
reaction mixture was treated to afford the desired compound (2.47
g) as a syrup.
[1377] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.36 (4H, m), 1.38-1.90
(8H, m), 2.51-2.63 (1H, m), 2.67 (1H, dd, J=6.5, 13.5 Hz), 2.85
(1H, dd, J=8.5, 13.5 Hz), 3.48-3.56 (1H, m), 3.72-3.94 (3H, m),
3.96-4.16 (4H, m), 4.70 (1H, t, J=3.5 Hz), 6.83 (2H, d, J=8.5 Hz),
7.06 (2H, d, J=8.5 Hz).
[1378] (e) Ethyl
2-butyl-3-[4-(2-hydroxyethoxy)phenyl]propionate
[1379] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-butyl-3-[4-[2-(tetrahydropyran-2-y- loxy)ethoxy]phenyl]propionate
(2.47 g), which is the product of Reference example 6(d), and
p-toluenesulfonic acid monohydrate (1.24 g) and the reaction
mixture was treated to afford the desired compound (1.44 g) as a
syrup.
[1380] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.20-1.37 (3H, m), 1.39-1.70
(3H, m), 2.08 (1H, brs), 2.51-2.63 (1H, m), 2.68 (1H, dd, J=6.5,
13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.89-4.00 (2H, m),
4.02-4.11 (4H, m), 6.82 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz).
[1381] (f) Ethyl
2-butyl-3-[4-(2-methanesulfonyloxyethoxy)phenyl]propionat- e
[1382] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
2-butyl-3-[4-(2-hydroxyethoxy)phenyl- ]propionate (1.44 g), which
is the product of Reference example 6(e), triethylamine (2.04 ml)
and methanesulfonyl chloride (0.76 ml) and the reaction mixture was
treated to afford the desired compound (1.65 g) as a syrup.
[1383] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.39 (4H, m), 1.40-1.70
(2H, m), 2.52-2.61 (1H, m), 2.69 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.09 (3H, s), 4.06 (2H, q, J=7.0 Hz),
4.21 (2H, t, J=4.5 Hz), 4.55 (2H, t, J=4.5 Hz), 6.81 (2H, d, J=8.5
Hz), 7.09 (2H, d, J=8.5 Hz).
[1384] (g) Ethyl 3-[4-(2-azidoethoxy)phenyl]-2-butylpropionate
[1385] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-butyl-3-[4-(2-methanesulfonyloxyet- hoxy)phenyl]propionate (1.65
g), which is the product of Reference example 6(f), and sodium
azide (0.95 g) and the reaction mixture was treated to afford the
desired compound (1.62 g) as a syrup.
[1386] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87(3H, t,
J=7.0Hz), 1.16 (3H, t, J=7.0Hz), 1.20-1.39 (3H, m), 1.40-1.70 (3H,
m), 2.53-2.64 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86 (1H, dd,
J=8.5, 13.5 Hz), 3.58 (2H, t, J=5.0 Hz), 4.06 (2H, q, J=7.0 Hz),
4.12 (2H, t, J=5.0 Hz), 6.82 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz).
[1387] (h) Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate
[1388] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-butylp- ropionate (1.62 g), which is
the product of Reference example 6(g), and palladium on carbon (5%,
243 mg) and the reaction mixture was treated to afford the title
compound (1.49 g) as a syrup.
Reference Example 7
Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-(3-phenylpropyl)propionate
[1389] (a) Diethyl 2-methyl-2-(3-phenylpropyl)malonate
[1390] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl 2-methylmalonate
(3.48 g), 3-phenylpropyl bromide (3.98 g) and sodium hydride (55%
suspension in oil, 0.96 g) and the reaction mixture was treated to
afford the desired compound (4.63 g) as a syrup.
[1391] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (6H, t,
J=7.0 Hz), 1.34 (3H, s), 1.50-1.63 (2H, m), 1.88-1.94 (2H, m), 2.62
(2H, t, J=7.5 Hz), 4.16 (4H, q, J=7.0 Hz), 7.15-7.30 (5H, m).
[1392] (b) Ethyl 2-methyl-5-phenylvalerate
[1393] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-methyl-2-(3-phenylpropyl)malonat- e (4.63 g) and potassium
hydroxide (3.55 g) and the reaction mixture was treated to afford
the desired compound (3.18 g) as a syrup.
[1394] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.14 (3H, d,
J=7.0 Hz), 1.24 (3H, t, J=7.0 Hz), 1.37-1.54 (1H, m), 1.55-1.87
(3H, m), 2.37-2.44 (1H, m), 2.61 (2H, t, J=7.5 Hz), 4.12 (2H, q,
J=7.0 Hz), 7.10-7.35 (5H, m).
[1395] (c) Ethyl
2-(4-benzyloxybenzyl)-2-methyl-5-phenylvalerate
[1396] A solution of n-butyllithium in hexane (1.65M, 19.4 ml) was
added dropwise over a period of 20 minutes at -60.degree. C. to a
solution of diisopropylamine (3.23 g) in anhydrous tetrahydrofuran
(60 ml). The mixture was stirred at 0.degree. C. for 30 minutes. To
this mixture a solution of 2-methyl-5-phenylvalerate (7.05 g) in
anhydrous tetrahydrofuran (30 ml) was added dropwise over a period
of 20 minutes at -70.degree. C. and the mixture was stirred at
-70.degree. C. for 40 minutes. To this reaction mixture a solution
of 4-benzyloxybenzyl chloride (9.68 g) in anhydrous tetrahydrofuran
(80 ml) was added dropwise at -70.degree. C. The mixture was
stirred at -70.degree. C. for 3 hours. At the end of this time the
reaction mixture was partitioned between ethyl acetate and water.
The ethyl acetate layer was separated and washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and then concentrated under reduced pressure. The residue
was purified via chromatography on a silica gel column using
hexane/ethyl acetate=15/1 as the eluant to afford the desired
compound (1.88 g) as a syrup.
[1397] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.06 (3H, s),
1.19 (3H, t, J=7.0 Hz), 1.38-1.87 (4H, m), 2.51-2.61 (2H, m), 2.62
(1H, d, J=13.5 Hz), 2.93 (1H, d, J=13.5 Hz), 4.08 (2H, q, J=7.0
Hz), 5.01 (2H, s), 6.84 (2H, d, J=8.5 Hz), 6.97 (2H, d, J=8.5 Hz),
7.14-7.49 (10H, m).
[1398] (d) Ethyl 2-(4-hydroxybenzyl)-2-methyl-5-phenylvalerate
[1399] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
2-(4-benzyloxybenzyl)-2-methyl-5-phe- nylvalerate (1.88 g), which
is the product of Reference example 7(c), and palladium on carbon
(5%, 0.28 g) and the reaction mixture was treated to afford the
desired compound (1.58 g) as a syrup.
[1400] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.06 (3H, s),
1.20 (3H, t, J=7.0 Hz), 1.35-1.85 (4H, m), 2.56-2.68 (2H, m), 2.60
(1H, d, J=13.5 Hz), 2.92 (1H, d, J=13.5 Hz), 4.09 (2H, q, J=7.0
Hz), 5.18 (1H, brs), 6.68 (2H, d, J=8.5 Hz), 6.91 (2H, d, J=8.5
Hz), 7.05-7.36 (5H, m).
[1401] (e) Ethyl
2-methyl-2-(3-phenylpropyl)-3-[4-[2-(tetrahydropyran-2-yl-
oxy)ethoxy]phenyl]propionate
[1402] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
2-(4-hydroxybenzyl)-2-methyl-5-pheny- lvalerate (1.58 g), which is
the product of Reference example 7(d),
2-(2-bromoethoxy)tetrahydropyran (0.94 g) and potassium carbonate
(1.86 g) in dimethylacetamide and the reaction mixture was treated
to afford the desired compound (1.64 g) as a syrup.
[1403] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.05 (3H, s),
1.21 (3H, t, J=7.10 Hz), 1.35-1.90 (10H, m), 2.50-2.64 (2H, m),
2.62 (1H, d, J=13.5 Hz), 2.93 (1H, d, J=13.5 Hz), 3.45-3.56 (1H,
m), 3.67-4.15 (7H, m), 4.71 (1H, t, J=3.5 Hz), 6.80 (2H,-d, J=8.5
Hz), 6.96 (2H, d, J=8.5 Hz), 7.11-7.31 (5H, m).
[1404] (f) Ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-methyl-2-(3-phenylpropyl)-
propionate
[1405] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-methyl-2-(3-phenylpropyl)-3-[4-[2--
(tetrahydropyran-2-yloxy)ethoxy]phenyl]propionate (1.64 g), which
is the product of Reference example 7(e), and p-toluenesulfonic
acid monohydrate (0.68 g) and the reaction mixture was treated to
afford the desired compound (0.95 g) as a syrup.
[1406] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.06 (3H, s),
1.21 (3H, t, J=7.0 Hz), 1.38-1.82 (4H, m), 2.04 (1H, brs),
2.56-2.65 (3H, m), 2.94 (1H, d, J=13.5 Hz), 3.87-3.97 (2H, m),
3.99-4.14 (4H, m), 6.79 (2H, d, J=8.5 Hz), 6.98 (2H, d, J=8.5 Hz),
7.10-7.31 (5H, m).
[1407] (g) Ethyl
3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-methyl-2-(3-ph-
enylpropyl)propionate
[1408] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-meth-
yl-2-(3-phenylpropyl)propionate (0.95 g), which is the product of
Reference example 7(f), triethylamine (1.07 ml) and methanesulfonyl
chloride (0.40 ml) and the reaction mixture was treated to afford
the desired compound (1.16 g) as a syrup.
[1409] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.05 (3H, s),
1.21 (3H, t, J=7.0 Hz), 1.38-1.82 (4H, m), 2.59 (2H, t, J=7.0 Hz),
2.62 (1H, d, J=13.5 Hz), 2.94 (1H, d, J=13.5 Hz), 3.08 (3H, s),
4.09 (2H, q, J=7.0 Hz), 4.21 (2H, t, J=4.5 Hz), 4.56 (2H, t, J4.5
Hz), 6.77 (2H, d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz), 7.15-7.31 (5H,
m).
[1410] (h) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-methyl-2-(3-phenylpropyl)pr-
opionate
[1411] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
3-[4-(2-methanesulfonyloxyethoxy)phe-
nyl]-2-methyl-2-(3-phenylpropyl)propionate (1.16 g), which is the
product of Reference example 7(g), and sodium azide (0.50 g) and
the reaction mixture was treated to afford the desired compound
(0.86 g) as a syrup.
[1412] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.06 (3H, s),
1.21 (3H, t, J=7.0 Hz), 1.38-1.82 (4H, m), 2.56-2.65 (3H, m), 2.94
(1H, d, J=13.5 Hz), 3.58 (2H, t, J=5.0 Hz), 4.05-4.14 (4H, m), 6.78
(2H, d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz), 7.15-7.31 (5H, m).
[1413] (i) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-(3-phenylpropyl)pr-
opionate
[1414] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-methyl- -2-(3-phenylpropyl)propionate
(0.86 g), which is the product of Reference example 7(h), and
palladium on carbon (5%, 129 mg) and the reaction mixture was
treated to afford the title compound (0.80 g) as a syrup.
Reference Example 8
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-phenoxypropionate
[1415] (a) Ethyl
3-(4-benzyloxyphenyl)-2-methyl-2-phenoxypropionate
[1416] In a similar manner to that described in Reference example
7(c), a reaction was carried out using ethyl 2-phenoxypropionate
(6.15 g), 4-benzyloxybenzyl chloride (9.62 g) and dicyclohexylamine
(5.78 g) instead of diisopropylamine and the reaction mixture was
treated to afford the desired compound (4.97 g) as a syrup.
[1417] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.40 (3H, s), 3.11 (1H, d, J=14.0 Hz), 3.28 (1H, d,
J=14.0 Hz), 4.19 (2H, q, J=7.0 Hz), 5.04 (2H, s), 6.75-7.02 (5H,
m), 7.11-7.47 (9H, m).
[1418] (b) Ethyl
3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionate
[1419] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-methyl-2-phe- noxypropionate (4.97 g),
which is the product of Reference example 8(a), and palladium on
carbon (5%, 0.75 g) and the reaction mixture was treated to afford
the desired compound (3.85 g) as a syrup.
[1420] 1.20 (3H, t, J=7.0 Hz), 1.40 (3H, s), 3.10 (1H, d, J=14.0
Hz), 3.24 (1H, d, J=14.0 Hz), 4.20 (2H, q, J=7.0 Hz), 6.13 (1H,
brs), 6.74 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5 Hz), 6.96 (1H, t,
J=7.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.20 (2H, dd, J=7.5, 8.5
Hz).
[1421] (c) Ethyl
2-methyl-2-phenoxy-3-[4-[2-(tetrahydropyran-2-yloxy)ethox-
y]phenyl]propionate
[1422] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-methyl-2-pheno- xypropionate (1.55 g), which
is the product of Reference example 8(b),
2-(2-bromoethoxy)tetrahydropyran (1.08 g) and potassium carbonate
(2.14 g) in dimethylacetamide and the reaction mixture was treated
to afford the desired compound (1.60 g) as a syrup.
[1423] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 1.39 (3H, s), 1.45-1.90 (6H, m), 3.11 (1H, d, J=13.5
Hz), 3.27 (1H, d, J=13.5 Hz), 3.49-3.56 (1H, m), 3.75-4.15 (5H, m),
4.20 (2H, q, J=7.0 Hz), 4.71 (1H, t, J=3.5 Hz), 6.78-6.90 (4H, m),
6.97 (1H, t, J=7.5 Hz), 7.11-7.25 (4H, m).
[1424] (d) Ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-methyl-2-phenoxypropionat- e
[1425] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-methyl-2-phenoxy-3-[4-[2-(tetrahyd-
ropyran-2-yloxy)ethoxy]phenyl]propionate (1.60 g), which is the
product of Reference example 8(c), and p-toluenesulfonic acid
monohydrate (0.70 g) and the reaction mixture was treated to afford
the desired compound (1.10 g) as a syrup.
[1426] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 1.40 (3H, s), 2.09 (1H, brs), 3.11 (1H, d, J=13.5 Hz),
3.28 (1H, d, J=13.5 Hz), 3.91-4.00 (2H, m), 4.07 (2H, t, J=4.5 Hz),
4.21 (2H, q, J=7.0 Hz), 6.81-6.90 (4H, m), 6.97 (1H, t, J=7.5 Hz),
7.13-7.28 (4H, m).
[1427] (e) Ethyl
3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-methyl-2-pheno-
xypropionate
[1428] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
3-[4-(2-hydroxyethoxy)phenyl]-2-meth- yl-2-phenoxypropionate (1.10
g), which is the product of Reference example 8(d), triethylamine
(0.49 ml) and methanesulfonyl chloride (0.25 ml) and the reaction
mixture was treated to afford the desired compound (1.42 g) as a
syrup.
[1429] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 1.40 (3H, s), 3.07 (3H, s), 3.11 (1H, d, J=14.0 Hz),
3.29 (1H, d, J=14.0 Hz), 4.17-4.25 (4H, m), 4.56 (2H, t, J=4.5 Hz),
6.81-6.93 (4H, m), 6.98 (1H, t, J=7.5 Hz), 7.17-7.26 (4H, m).
[1430] (f) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-methyl-2-phenoxypropionate
[1431] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
3-[4-(2-methanesulfonyloxyethoxy)phe-
nyl]-2-methyl-2-phenoxypropionate (1.42 g), which is the product of
Reference example 8(e), and sodium azide (0.66 g) and the reaction
mixture was treated to afford the desired compound (0.82 g) as a
syrup.
[1432] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.22 (3H, t,
J=7.0 Hz), 1.40 (3H, s), 3.12 (1H, d, J=14.0 Hz), 3.29 (1H, d,
J=14.0 Hz), 3.58 (2H, t, J=5.0 Hz), 4.13 (2H, t, J=5.0 Hz), 4.20
(2H, q, J=7.0 Hz), 6.82-6.89 (4H, m), 6.97 (1H, t, J=7.5 Hz),
7.17-7.27 (4H, m).
[1433] (g) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-methyl-2-phenoxypropionate
[1434] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-methyl- -2-phenoxypropionate (0.82
g), which is the product of Reference example 8(f), and palladium
on carbon (5%, 123 mg) and the reaction mixture was treated to
afford the title compound (0.76 g) as a syrup.
Reference Example 9
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy)-2-methylpropionate
[1435] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-isopropylphenoxy)-2-methylprop-
ionate
[1436] In a similar manner to that described in Reference example
7(c), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)propionate (4.72 g) and 4-benzyloxybenzyl
chloride (6.00 g) and dicyclohexylamine (3.62 g) instead of
diisopropylamine and the reaction mixture was treated to afford the
desired compound (6.16 g) as a syrup.
[1437] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.21 (3H, t, J=7.5 Hz), 1.38 (3H, s), 2.83 (1H, septet,
J=7.0 Hz), 3.11 (1H, d, J=13.5 Hz), 3.25 (1H, d, J=13.5 Hz), 4.20
(2H, q, J=7.5 Hz), 5.05 (2H, s), 6.75 (2H, d, J=8.5 Hz), 6.91 (2H,
d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz),
7.30-7.45 (5H, m).
[1438] (b) Ethyl
3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)-2-methylpropio- nate
[1439] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-isopropyl- phenoxy)-2-methylpropionate
(6.16 g), which is the product of Reference example 9(a), and
palladium on carbon (5%, 1.00 g) and the reaction mixture was
treated to afford the title compound (4.18 g) as a syrup.
[1440] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.22 (3H, t, J=7.5 Hz), 1.38 (3H, s), 2.83 (1H, septet,
J=7.0 Hz), 3.10 (1H, d, J=13.5 Hz), 3.24 (1H, d, J=13.5 Hz), 4.20
(2H, q, J=7.5 Hz), 4.81 (1H, s), 6.75 (4H, d, J=8.5 Hz), 7.06 (2H,
d, J=8.5 Hz), 7.13 (2H, d, J=8.5 Hz).
[1441] (c) Ethyl
2-(4-isopropylphenoxy)-2-methyl-3-[4-[2-(tetrahydropyran--
2-yloxy)ethoxy]phenyl]propionate
[1442] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-(4-isopropylph- enoxy)-2-methylpropionate
(1.00 g), which is the product of Reference example 9(b),
2-(2-bromoethoxy)tetrahydropyran (1.84 g) and potassium carbonate
(1.62 g) in dimethylacetamide and the reaction mixture was treated
to afford the desired compound (1.06 g) as a syrup.
[1443] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.36 (3H, s), 1.48-1.90 (6H, m),
2.83 (1H, septet, J=7.0 Hz), 3.10 (1H, d, J=13.5 Hz), 3.25 (1H, d,
J=13.5 Hz), 3.48-3.57 (1H, m), 3.78-3.96 (2H, m), 4.01-4.25 (5H,
m), 4.70-4.73 (1H, m), 6.75 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5
Hz), 7.06 (2H, d, J=8.5 Hz), 7.17 (2H, d, J=8.5 Hz).
[1444] (d) Ethyl
2-(4-isopropylphenoxy)-3-[4-(2-hydroxyethoxy)phenyl]-2-me-
thylpropionate
[1445] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)-2-methyl-3-[4-
-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl]propionate (1.06 g),
which is the product of Reference example 9(c), and
p-toluenesulfonic acid monohydrate (0.60 g) and the reaction
mixture was treated to afford the desired compound (0.66 g) as a
syrup.
[1446] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.37 (3H, s), 2.01 (1H, t, J=6.0
Hz), 2.83 (1H, septet, J=7.0 Hz), 3.11 (1H, d, J=13.5 Hz), 3.26
(1H, d, J=13.5 Hz), 3.93-4.00 (2H, m), 4.054.10 (2H, m), 4.21 (2H,
q, J=7.0 Hz), 6.75 (2H, d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz), 7.06
(2H, d, J=8.5 Hz), 7.19 (2H, d, J=8.5 Hz).
[1447] (e) Ethyl 2-(4-isopropylphenoxy)-
3-[4-(2-methanesulfonyloxyethoxy)- phenyl]-2-methylpropionate
[1448] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)-3-[4-(2-hydro-
xyethoxy)phenyl]-2-methylpropionate (0.66 g), which is the product
of Reference example 9(d), triethylamine (0.36 ml) and
methanesulfonyl chloride (0.15 ml) and the reaction mixture was
treated to afford the desired compound (0.64 g) as a syrup.
[1449] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.37 (3H, s), 2.83 (1H, septet,
J=7.0 Hz), 3.09 (3H, s), 3.11 (1H, d, J=13.5 Hz), 3.26 (1H, d,
J=13.5 Hz), 4.21 (2H, q, J=7.0 Hz), 4.22-4.26 (2H, m), 4.55-4.59
(2H, m), 6.75 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5 Hz), 7.06 (2H,
d, J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz).
[1450] (f) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-isopropylphenoxy)-2-meth-
ylpropionate
[1451] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-(4-isopropylphenoxy)-3-[4-(2-metha-
nesulfonyloxyethoxy)phenyl]-2-methylpropionate (0.64 g), which is
the product of Reference example 9(e), and sodium azide (0.27 g)
and the reaction mixture was treated to afford the desired compound
(0.56 g) as a syrup.
[1452] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.37 (3H, s), 2.83 (1H, septet,
J=7.0 Hz), 3.11 (1H, d, J=13.5 Hz), 3.26 (1H, d, J=13.5 Hz), 3.59
(2H, t, J=5.0 Hz), 4.14 (2H, t, J=5.0 Hz), 4.21 (2H, q, J=7.0 Hz),
6.75 (2H, d, J=8.5 Hz), 6.85 (2H, d, J=8.5 Hz), 7.06 (2H, d, J=8.5
Hz), 7.19 (2H, d, J=8.5 Hz).
[1453] (g) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-isopropylphenoxy)-2-meth-
ylpropionate
[1454] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-iso-
propylphenoxy)-2-methylpropionate (0.56 g), which is the product of
Reference example 9(f), and palladium on carbon (5%, 60 mg) and the
reaction mixture was treated to afford the title compound (0.51 g)
as a syrup.
[1455] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 1.23 (3H, t, J=7.0 Hz), 1.37 (3H, s), 1.63 (2H, brs),
2.83 (1H, septet, J=7.0 Hz), 3.08 (2H, t, J=5.0 Hz), 3.10 (1H, d,
J=13.5 Hz), 3.25 (1H, d, J=13.5 Hz), 3.92-4.13 (2H, m), 4.21 (2H,
q, J=7.0 Hz), 6.75 (2H, d, J=8.5 Hz), 6.84 (2H, d, J=8.5 Hz), 7.06
(2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz).
Reference Example 10
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-butyl-2-methylpropionate
[1456] (a) Ethyl 2-(4-benzyloxybenzyl)-2-methylcaproate
[1457] In a similar manner to that described in Reference example
7(c), a reaction was carried out using ethyl
2-(4-benzyloxybenzyl)caproate (2.04 g) and methyl iodide (1.12 ml)
instead of 4-benzyloxybenzyl chloride and cyclohexylisopropylamine
(1.48 ml) instead of diisopropylaamine and the reaction mixture was
treated to afford the desired compound (1.80 g) as a syrup.
[1458] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.45 (8H, m), 1.63-1.79 (1H, m), 2.63
(1H, d, J=13.5 Hz), 2.96 (1H, d, J=13.5 Hz), 4.10 (2H, q, J=7.0
Hz), 5.03 (2H, s), 6.86 (2H, d, J=8.5 Hz), 7.02 (2H, d, J=8.5 Hz),
7.25-7.46 (5H, m).
[1459] (b) Ethyl 2-butyl-3-(4-hydroxyphenyl)-2-methylpropionate
[1460] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
2-(4-benzyloxybenzyl)-2-methylcaproa- te (3.95 g), which is the
product of Reference example 10(a), and palladium on carbon (5%,
0.40 g) and the reaction mixture was treated to afford the desired
compound (2.95 g) as a syrup.
[1461] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.45 (8H, m), 1.62-1.79 (1H, m), 2.61
(1H, d, J=13.5 Hz), 2.95 (1H, d, J=13.5 Hz), 4.10 (2H, q, J=7.0
Hz), 4.80 (1H, brs), 6.71 (2H, d, J=8.5 Hz), 6.96 (2H, d, J=8.5
Hz).
[1462] (c) Ethyl
2-butyl-2-methyl-3-[4-[2-(tetrahydropyran-2-yloxy)ethoxy]-
phenyl]propionate
[1463] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
2-butyl-3-(4-hydroxyphenyl)-2-methyl- propionate (2.95 g), which is
the product of Reference example 10(b),
2-(2-bromoethoxy)tetrahydropyran (4.66 g) and potassium carbonate
(4.62 g) in dimethylacetamide and the reaction mixture was treated
to afford the desired compound (4.18 g) as a syrup.
[1464] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.05 (3H, s), 1.11-1.43 (8H, m), 1.47-1.90 (7H, m), 2.62
(1H, d, J=13.5 Hz), 2.95 (1H, d, J=13.5 Hz), 3.48-3.57 (1H, m),
3.64-4.18 (7H, m), 4.67-4.72 (1H, m), 6.81 (2H, d, J=8.5 Hz), 7.00
(2H, d, J=8.5 Hz).
[1465] (d) Ethyl
2-butyl-3-[4-(2-hydroxyethoxy)phenyl]-2-methylpropionate
[1466] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-butyl-2-methyl-3-[4-[2-(tetrahydro-
pyran-2-yloxy)ethoxy]phenyl]propionate (4.18 g), which is the
product of Reference example 10(c), and p-toluenesulfonic acid
monohydrate (2.61 g) and the reaction mixture was treated to afford
the desired compound (2.73 g) as a syrup.
[1467] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.47 (8H, m), 1.65-1.78 (1H, m), 2.04
(1H, brs), 2.63 (1H, d, J=13.5 Hz), 2.96 (1H, d, J=13.5 Hz),
3.91-3.98 (2H, m), 4.04-4.17 (4H, m), 6.81 (2H, d, J=8.5 Hz), 7.02
(2H, d, J=8.5 Hz).
[1468] (e) Ethyl
2-butyl-3-[4-(2-methanesulfonyloxyethoxy)phenyl]-2-methyl-
propionate
[1469] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
2-butyl-3-[4-(2-hydroxyethoxy)phenyl- ]-2-methylpropionate (2.73
g), which is the product of Reference example 10(d), triethylamine
(1.85 ml) and methanesulfonyl chloride (0.75 ml) and the reaction
mixture was treated to afford the desired compound (3.17 g) as a
syrup.
[1470] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.44 (8H, m), 1.66-1.80 (1H, m), 2.62
(1H, d, J=13.5 Hz), 2.97 (1H, d, J=13.5 Hz), 3.08 (3H, s), 4.11
(2H, q, J=7.5 Hz), 4.20-4.23 (2H, m), 4.54-4.58 (2H, m), 6.79 (2H,
d, J=8.5 Hz), 7.03 (2H, d, J=8.5 Hz).
[1471] (f) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-butyl-2-methylpropionate
[1472] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-butyl-3-[4-(2-methanesulfonyloxyet-
hoxy)phenyl]-2-methylpropionate (3.17 g), which is the product of
Reference example 10(e), and sodium azide (1.60 g) and the reaction
mixture was treated to afford the desired compound (2.80 g) as a
syrup.
[1473] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.44 (8H, m), 1.66-1.78 (1H, m), 2.63
(1H, d, J=13.5 Hz), 2.96 (1H, d, J=13.5 Hz), 3.58 (2H, t, J=5.0
Hz), 4.11 (2H, q, J=7.5 Hz), 4.12 (2H, t, J=5.0 Hz), 6.81 (2H, d,
J=8.5 Hz), 7.03 (2H, d, J=8.5 Hz).
[1474] (g) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butyl-2-methylpropionate
[1475] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-butyl-- 2-methylpropionate (2.73 g),
which is the product of Reference example 10(f), and palladium on
carbon (5%, 270 mg) and the reaction mixture was treated to afford
the title compound (2.42 g) as a syrup.
[1476] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.06 (3H, s), 1.10-1.43 (9H, m), 1.71 (2H, brs), 2.62
(1H, d, J=13.5 Hz), 2.96 (1H, d, J=13.5 Hz), 3.07 (2H, t, J=5.0
Hz), 3.91-4.10 (2H, m), 4.11 (2H, q, J=7.0 Hz), 6.80 (2H, d, J=8.5
Hz), 7.01 (2H, d, J=8.5 Hz).
Reference Example 11
Ethyl
2-butyl-3-[4-[2-(4'-dimethoxymethylbiphenyl-4-carbonylamino)ethoxy]p-
henyl]propionate
[1477] (a) Methyl 4'-dimethoxymethylbiphenyl-4-carboxylate
[1478] Methyl orthoformate (4.55 ml) and amberlyst 15 (200 mg) were
added to a solution of methyl 4'-formylbiphenyl-4-carboxylate (2.00
g) in methanol (20 ml). The mixture was allowed to stand at ambient
temperature for 14 hours. The amberlyst was removed by filtration
and the filtrate was concentrated under reduced pressure. Excess
methyl orthoformate was azeotropicaly evaporated off with toluene.
The residue was crystallized from diisopropyl ether to afford the
desired compound (2.23 g) as colorless crystals.
[1479] mp 76-77.degree. C.
[1480] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.37 (6H, s),
3.94 (3H, s), 5.45 (1H, s), 7.55 (2H, d, J=8.5 Hz), 7.64 (2H, d,
J=8.5 Hz), 7.67 (2H, d, J=8.5 Hz), 8.11 (2H, d, J=8.5 Hz).
[1481] (b) 4'-Dimethoxymethylbiphenyl-4-carboxylic acid
[1482] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
4'-dimethoxymethylbiphenyl-4-carboxylate (1.89 g), which is the
product of Reference example 11(a), and aqueous sodium hydroxide
(1N, 9.90 ml) and the reaction mixture was treated to afford the
desired compound (1.80 g) as colorless crystals.
[1483] mp 164.degree. C.
[1484] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.28 (6H, s), 5.45 (1H, s), 7.51 (2H, d, J=8.5 Hz),
7.76 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz), 8.02 (2H, d, J=8.5
Hz).
[1485] (c) Ethyl 2-butyl-3-[4-[2-(4'-dimethoxymethylbiphenyl-4-
carbonylamino)ethoxy]phenyl]propionate
[1486] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (1.81 g), which is
the product of Reference example 6,
4'-dimethoxymethylbiphenyl-4-carboxylic acid (1.68 g), which is the
product of reference example 11(b), and carbonyldiimidazole (1.20
g) and the reaction mixture was treated to afford the desired
compound (2.77 g) as a pale brown solid.
[1487] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.36 (4H, m), 1.38-1.49
(1H, m), 1.51-1.71 (1H, m), 2.52-2.63 (1H, m), 2.68 (1H, dd, J=6.5,
13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.36 (6H, s), 3.88 (2H, q,
J=5.0 Hz), 4.05 (2H, q, J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz), 5.45
(1H, s), 6.65 (1H, brt), 6.83 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz), 7.54 (2H, d, J=8.5 Hz), 7.62 (2H, d, J=8.5 Hz), 7.66 (2H, d,
J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz).
Reference Example 12
Ethyl 2-butyl-3-[4-[2-(4'-methoxycarbonylbiphenyl-4-
carbonylamino)ethoxy]phenyl]propionate
[1488] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (375 mg), which is
the product of Reference example 6,
4'-methoxycarbonylbiphenyl-4-carboxylic acid (328 mg) and
carbonyldiimidazole (225 mg) and the reaction mixture was treated
to afford the title compound (257 mg) as colorless crystals.
[1489] mp 93-95.degree. C.
[1490] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.86 (3H, t,
J=6.5 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.36 (4H, m), 1.40-1.67
(2H, m), 2.52-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.88
(1H, dd, J=8.5, 13.5 Hz), 3.89 (2H, t, J=5.0 Hz), 3.95 (3H, s),
4.05 (2H, q, J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 6.63 (1H, brs),
6.84 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.68 (2H, d, J=8.5
Hz), 7.69 (2H, d, J=8.5 Hz), 7.88 (2H, d, J=8.5 Hz), 8.12 (2H, d,
J=8.5 Hz).
Reference Example 13
3'-Hydroxybiphenyl-4-carboxylic acid
[1491] A solution of boron tribromide in dichloromethane (1N, 24.8
ml) was added to a solution of methyl
3'-methoxybiphenyl-4-carboxylate (2.00 g) in anhydrous
dichloromethane (10 ml) at -70.degree. C. The mixture was stirred
at ambient temperature for 4 hours and a mixture of ice and water
was added to the reaction mixture in an ice bath and then the
mixture was stirred for 30 minutes. The reaction mixture was
concentrated under reduced pressure. The residue was partitioned
between ethyl acetate and water and the layers were separated. The
ethyl acetate layer was dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was crystallized
from a mixture of hexane and diisopropyl ether to afford the title
compound (1.82 g) as pale yellow crystals.
[1492] mp 250-253.degree. C.
[1493] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 6.89 (1H, d,
J=8.0 Hz), 7.11 (1H, d, J=8.0 Hz), 7.13 (1H, s) 7.28 (1H, t, J=8.0
Hz), 7.64 (2H, d, J=8.5 Hz), 8.12 (2H, d, J=8.5 Hz).
Reference Example 14
Ethyl
2-butyl-3-[4-[2-(3'-dimethoxymethylbiphenyl-4-carbonylamino)ethoxy]p-
henyl]propionate
[1494] (a) Methyl 3'-formylbiphenyl-4-carboxylate
[1495] A solution of tetrakis(triphenylphosphine)palladium (297 mg)
was added to a solution of 3-formylphenylboric acid (3.00 g) and
methyl 4-bromobenzoic acid (4.30 g) in a mixture of toluene (30
ml), ethanol (50 ml) and saturated aqueous sodium hydrogencarbonate
solution (30 ml) at ambient temperature. The mixture was heated at
reflux for 2 hours at 100.degree. C. The reaction mixture was
partitioned between ethyl acetate and water and the layers were
separated. The ethyl acetate layer was washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and concentrated under reduced pressure. The residue was
crystallized from diisopropyl ether to afford the title compound
(3.37 g) as colorless crystals.
[1496] mp 95-97.degree. C.
[1497] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.96 (3H, s),
7.65 (1H, d, J=7.5 Hz), 7.70 (2H, d, J=8.5 Hz), 7.88-7.93 (2H, m),
8.14 (1H, s), 8.15 (2H, d, J=8.5 Hz), 10.11 (1H, s).
[1498] (b) Methyl 3'-dimethoxymethylbiphenyl-4-carboxylate
[1499] In a similar manner to that described in Example 11(a), a
reaction was carried out using methyl
3'-formylbiphenyl-4-carboxylate (1.60 g), which is the product of
Reference example 14(a), methyl orthoformate (3.64 ml) and
amberlyst 15 (160 mg) and the reaction mixture was treated to
afford the desired compound (1.91 g) as a syrup.
[1500] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.37 (6H, s),
3.94 (3H, s), 5.46 (1H, s), 7.47 (1H, d, J=4.5 Hz), 7.49 (1H, d,
J=2.5 Hz), 7.57-7.64 (1H, m), 7.68 (2H, d, J=8.5 Hz), 7.72 (1H, s),
8.11 (2H, d, J=8.5 Hz).
[1501] (c) 3'-Dimethoxymethylbiphenyl-4-carboxylic acid
[1502] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
3'-dimethoxymethylbiphenyl-4-carboxylate (1.91 g), which is the
product of Reference example 14(b), and aqueous sodium hydroxide
(1N, 10.0 ml) and the reaction mixture was treated to afford the
desired compound (1.55 g) as colorless crystals.
[1503] mp 130-13l.degree. C.
[1504] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.38 (6H, s),
5.48 (1H, s), 7.49 (1H, d, J=5.0 Hz), 7.49 (1H, d, J=3.5 Hz),
7.59-7.66 (1H, m), 7.73 (2H, d, J=8.5 Hz), 7.75 (1H, s), 8.19 (2H,
d, J=8.5 Hz).
[1505] (d) Ethyl
2-butyl-3-[4-[2-(3'-dimethoxymethylbiphenyl-4-carbonylami-
no)ethoxy]phenyl]propionate
[1506] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (1.55 g), which is
the product of Reference example 6,
3'-dimethoxymethylbiphenyl-4-carboxylic acid (1.44 g), which is the
product of reference example 14(c), and carbonyldiimidazole (1.03
g) and the reaction mixture was treated to afford the desired
compound (2.72 g) as a syrup.
[1507] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.21-1.35 (4H, m), 1.39-1.56
(1H, m), 1.58-1.67 (1H, m), 2.53-2.65 (1H, m), 2.69 (1H, dd, J=6.5,
13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.37 (6H, s), 3.89 (2H, q,
J=5.0 Hz), 4.06 (2H, q, J=7.0 Hz), 4.15 (2H, t, J=5.0 Hz), 5.45
(1H, s), 6.64(1H, brt), 6.84 (2H. d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz), 7.46 (1H, d, J=5.0 Hz), 7.47 (1H, d, J=3.0 Hz), 7.54-7.61 (1H,
m), 7.68 (2H, d, J=8.5 Hz), 7.71 (1H, s), 7.85 (2H, d, J=8.5
Hz).
Reference Example 15
Sodium
2-butyl-3-[4-[2-(3'-methoxymethoxymethylbiphenyl-4-carbonylamino)et-
hoxy]phenyl]propionate
[1508] (a) Methyl 3'-hydroxymethylbiphenyl-4-carboxylate
[1509] Sodium borohydride (132 mg) was added to a solution of
methyl 3'-formylbiphenyl-4-carboxylate (720 mg), which is the
product of Reference example 14(a), in ethanol (50 ml) at ambient
temperature. The mixture was stirred under an atmosphere of
nitrogen for 50 minutes. The reaction mixture was quenched with 50%
acetic acid and concentrated under reduced pressure. The residue
was partitioned between ethyl acetate and water and the layers were
separated. The ethyl acetate layer was washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and concentrated under reduced pressure. The residue was
crystallized from diisopropyl ether to afford the desired compound
(522 mg) as colorless crystals.
[1510] mp 88-89.degree. C.
[1511] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.95 (3H, s),
4.79 (2H, s), 7.40 (1H, d, J=7.5 Hz), 7.47 (1H, t, J=7.5 Hz), 7.56
(1H, d, J=7.5 Hz), 7.64 (1H, s), 7.67 (2H, d, J=8.5 Hz), 8.11 (2H,
d, J=8.5 Hz).
[1512] (b) Methyl 3'-methoxymethoxymethylbiphenyl-4-carboxylate
[1513] Chloromethylmethyl ether (0.24 ml) and diisopropylethylamine
(0.74 ml) was added to a solution of methyl
3'-hydroxymethylbiphenyl-4-carboxyl- ate (504 mg), which is the
product of Reference example 15(a), in anhydrous dichloromethane
(10 ml) at 0.degree. C. The mixture was stirred at 0.degree. C. for
1 hour and then allowed to stand at ambient temperature for 14
hours. The reaction mixture was concentrated under reduced
pressure. The residue was partitioned between ethyl acetate and
water and the layers were separated. The ethyl acetate layer was
washed with saturated aqueous sodium chloride solution and dried
over anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was purified via chromatography on a silica
gel column using hexane/ethyl acetate=2/1 as the eluant to afford
the desired compound (467 mg) as colorless crystals.
[1514] mp 54-55.degree. C.
[1515] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.44 (3H, s),
3.94 (3H, s), 4.67 (2H, s), 4.75 (2H, s), 7.39 (1H, d, J=7.5 Hz),
7.46 (1H, t, J=7.5 Hz), 7.56 (1H, d, J=7.5 Hz), 7.63 (1H, s), 7.67
(2H, d, J=8.5 Hz), 8.11 (2H, d, J=8.5 Hz).
[1516] (c) 3'-Methoxymethoxylmethylbiphenyl-4-carboxylic acid
[1517] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
3'-methoxymethoxymethylbiphenyl-4-carboxylate (445 mg), which is
the product of Reference example 15(b), and aqueous sodium
hydroxide (1N, 3.10 ml) and the reaction mixture was treated to
afford the desired compound (342 mg) as colorless crystals.
[1518] mp 126-127.degree. C.
[1519] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.45 (3H, s),
4.68 (2H, s), 4.76 (2H, s), 7.41 (1H, d, J=7.5 Hz), 7.47 (1H, t,
J=7.5 Hz), 7.58 (1H, d, J=7.5 Hz), 7.64 (1H, s), 7.71 (2H, d, J=8.5
Hz), 8.17 (2H, d, J=8.5 Hz).
[1520] (d) Ethyl
2-butyl-3-[4-[2-(3'-methoxymethoxymethylbiphenyl-4-
carbonylamino)ethoxy]phenyl]propionate
[1521] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (358 mg), which is
the product of Reference example 6,
3'-methoxymethoxymethylbiphenyl-4-carboxylic acid (333 mg), which
is the product of reference example 15(c), and carbonyldiimidazole
(238 mg) and the reaction mixture was treated to afford the desired
compound (573 mg) as a brown syrup.
[1522] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.39 (4H, m), 1.40-1.51
(1H, m), 1.54-1.67 (1H, m), 2.53-2.63 (1H, m), 2.68 (1H, dd, J=6.5,
13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 3.44 (3H, s), 3.88 (2H, q,
J=5.0 Hz), 4.05 (2H, q, J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz), 4.67
(2H, s), 4.74 (2H, s), 6.69 (1H, brt), 6.84 (2H, d, J=8.5 Hz), 7.08
(2H, d, J=8.5 Hz), 7.38 (1H, d, J=7.5 Hz), 7.45 (1H, t, J=7.5 Hz),
7.54 (2H, d, J=7.5 Hz), 7.60 (1H, s), 7.66 (2H, d, J=8.5 Hz), 7.86
(2H, d, J=8.5 Hz).
[1523] (e) Sodium
2-butyl-3-[4-[2-(3'-methoxymethoxymethylbiphenyl-4-carbo-
nylamino)ethoxy]phenyl]propionate
[1524] In a similar manner to that described in Example 2, a
reaction was carried out using ethyl
2-butyl-3-[4-[2-(3'-methoxymethoxymethylbiphenyl--
4-carbonylamino)ethoxy]phenyl]propionate (573 mg), which is the
product of Reference example 15(d), and aqueous sodium hydroxide
(1N, 2.00 ml) and the reaction mixture was treated to afford the
desired compound (472 mg) as a white powder.
[1525] mp 216-218.degree. C.
[1526] .sup.1H-NMR (270 MHz, deuterated methanol): .delta. ppm 0.85
(3H, t, J=7.0 Hz), 1.17-1.40 (4H, m), 1.46-1.60 (2H, m), 2.36-2.46
(1H, m), 2.52 (1H, dd, J=7.0, 13.5 Hz), 2.86 (1H, dd, J=7.5, 13.5
Hz), 3.41 (3H, s), 3.77 (2H, t, J=5.5 Hz), 4.14 (2H, t, J=5.5 Hz),
4.66 (2H, s), 4.73 (2H, s), 6.84 (2H, d, J=8.5 Hz), 7.13 (2H, d,
J=8.5 Hz), 7.38 (1H, d, J=7.5 Hz), 7.45 (1H, t, J=7.5 Hz), 7.60
(1H, d, J=7.5 Hz), 7.66 (1H, s), 7.72 (2H. d, J=8.5 Hz), 7.91 (2H,
d, J=8.5 Hz).
Reference Example 16
2'-Hydroxybiphenyl-4-carboxylic acid
[1527] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
2'-hydroxybiphenyl-4-carboxylate (498 mg) and aqueous sodium
hydroxide (1N, 4.81 ml) and the reaction mixture was treated to
afford the title compound (434 mg) as colorless crystals.
[1528] mp 176-178.degree. C.
[1529] .sup.1H-NMR (270 MHz, CDCl.sub.3/deuterated methanol=20/1):
.delta. ppm 6.92-7.05 (2H, m), 7.21-7.32 (2H, m), 7.64 (2H, d,
J=8.5 Hz), 8.15 (2H, d, J=8.5 Hz).
Reference Example 17
2-Butyl-3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carbonylamino)-
ethoxy]phenyl]propionic acid
[1530] (a) Methyl
4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carboxylate
[1531] A solution of 5-bromo-2-methoxymethoxy-1,3-dimethylbenzene
(3.35 g) in tetrahydrofuran (7.0 ml) was added dropwise a period of
15 minutes to a suspension of magnesium (327 mg) in tetrahydrofuran
(45 ml) at 65.degree. C. The mixture was stirred at 80.degree. C.
for 1 hour to prepare a Grignard reagent. This solution was added
dropwise to a solution of trimethyl borate (2.00 ml) in anhydrous
diethyl ether (20 ml) over a period of 30 minutes at -50.degree. C.
The mixture was stirred at room temperature for 2 hours. At the end
of this time the reaction was quenched with potassium
hydrogensulfate and partitioned between ethyl acetate and water.
The ethyl acetate layer was separated and washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and then concentrated under reduced pressure. The residue
was crystallized from diisopropyl ether to afford
4'-methoxymethoxy-3',5'-dimethylphenyl borate (1.04 g) as colorless
crystals. In a similar manner to that described in Reference
example 14(a), a reaction was carried out using
4'-methoxymethoxy-3',5'-dimethylp- henyl borate obtained above
(1.04 g), methyl 4-bromobenzoic acid (1.06 g) and
tetrakis(triphenylphosphine)palladium (96 mg) and the reaction
mixture was treated to afford the desired compound (1.36 g) as
colorless crystals.
[1532] mp 100-101.degree. C.
[1533] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.37 (6H, s),
3.64 (3H, s), 3.93 (3H, s), 5.01 (2H, s), 7.28 (2H, s), 7.61 (2H,
d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz).
[1534] (b) 4'-Methoxymethoxy-3',5'-dimethylbiphenyl-4-carboxylic
acid
[1535] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carbo- xylate (1.24 g)
and aqueous sodium hydroxide (1N, 8.20 ml) and the reaction mixture
was treated to afford the desired compound (0.99 g) as colorless
crystals.
[1536] mp 153-154.degree. C.
[1537] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.38 (6H, s),
3.64 (3H, s), 5.02 (2H, s), 7.30 (2H, s), 7.65 (2H, d, J=8.5 Hz),
8.14 (2H, d, J=8.5 Hz).
[1538] (c) Ethyl
2-butyl-3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-
-4-carbonylamino)ethoxy]phenyl]propionate
[1539] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (880 mg), which is
the product of Reference example 6,
4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carboxylic acid (859
mg), which is the product of reference example 17(b), and
carbonyldiimidazole (577 mg) and the reaction mixture was treated
to afford the desired compound (1.18 g) as colorless crystals.
[1540] mp 70-71.degree. C.
[1541] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.40 (4H, m), 1.41-1.77
(2H, m), 2.36 (6H, s), 2.52-2.63 (1H, m), 2.68 (1H, dd, J=6.5, 13.5
Hz), 2.86 (1H, dd, J=8.0, 13.5 Hz), 3.63 (3H, s), 3.88 (2H, q,
J=5.0 Hz), 4.05 (2H, q, J=7.0 Hz), 4.14 (2H, t, J=5.0 Hz), 5.00
(2H, s), 6.62 (1H, brt), 6.83 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5
Hz), 7.60 (2H, d, J=8.5 Hz), 7.82 (2H, d, J=8.5 Hz).
[1542] (d)
2-Butyl-3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-car-
bonylamino)ethoxy]phenyl]propionic acid
[1543] In a similar manner to that described in Example 2, a
reaction was carried out using ethyl
2-butyl-3-[4-[2-(4'-methoxymethoxy-3',5'-dimethyl-
biphenyl-4-carbonylamino)ethoxy]phenyl]propionate (1.01 g), which
is the product of Reference example 17(c) and aqueous sodium
hydroxide solution (1N, 3.60 ml) and the reaction mixture was
treated to afford the title compound (1.00 g) as a foam powder.
[1544] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.21-1.39 (4H, m), 1.40-1.70 (2H, m), 2.35 (6H, s),
2.56-2.65 (1H, m), 2.71 (1H, dd, J=6.5, 13.5 Hz), 2.89 (1H, dd,
J=8.5, 13.5 Hz), 3.63 (3H, s), 3.86 (2H, q, J=5.0 Hz), 4.12 (2H, t,
J=5.0 Hz), 5.00 (2H, s), 6.73 (1H, brt), 6.82 (2H, d, J=8.5 Hz),
7.09 (2H, d, J=8.5 Hz), 7.58 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5
Hz).
Reference Example 18
6-Isopropoxynicotinic acid
[1545] (a) Isopropyl 6-isopropoxynicotinate
[1546] Cesium carbonate (7.94 g) was added to a solution of
6-chloronicotinyl chloride (1.56 g) in isopropanol (20 ml). The
mixture was heated at reflux for 3 hours. The reaction mixture was
concentrated under reduced pressure. The residue was partitioned
between ethyl acetate and water and the layers were separated. The
ethyl acetate was dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=4/1 as the eluant to afford the desired compound (143 mg)
as colorless liquid.
[1547] H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.36 (12H, d, J=6.5
Hz), 5.24 (1H, septet, J=6.5 Hz), 5.39 (1H, septet, J=6.5 Hz), 6.68
(1H, d, J=8.5 Hz), 8.12 (1H, dd, J=2.5, 8.5 Hz), 8.81 (1H, d, J=2.5
Hz).
[1548] (b) 6-Isopropoxynicotinic acid
[1549] In a similar manner to that described in Example 2, a
reaction was carried out using isopropyl 6-isopropoxynicotinate
(130 mg), which is the product of Reference example 18(a) and
aqueous sodium hydroxide solution (1N, 0.87 ml) and the reaction
mixture was treated to afford the title compound (106 mg) as
crystals.
[1550] H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.38 (6H, d, J=6.0
Hz), 5.42 (1H, septet, J=6.0 Hz), 6.73 (1H, d, J=8.5 Hz), 8.18 (1H,
dd, J=2.5, 8.5 Hz), 8.92 (1H, d, J=2.5 Hz).
Reference Example 19
Ethyl
2-butyl-3-[4-[2-(3-phenylpropylamino)ethoxy]phenyl]propionate
[1551] 3-phenylpropionaldehyde (0.23 ml), sodium cyanoborohydride
(117 mg) and acetic acid (one drop) were added to a solution of
ethyl 3-[4-(2-aminoethoxy)phenyl]-2-butylpropionate (500 mg), which
is the product of Reference example 6, in ethanol (10 ml). The
mixture was stirred at ambient temperature for 18 hours. The
reaction mixture was concentrated under reduced pressure. The
residue was partitioned between ethyl acetate and water and the
layers were separated. The ethyl acetate solution was dried over
anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was purified via chromatography on silica gel
column using dichloromethane/methanol=19/1 as the eluant to afford
the desired compound (460 mg) as a pale yellow oil.
[1552] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.23-1.32 (4H, m), 1.40-1.95
(4H, m), 2.52-3.00 (9H, m), 3.99-4.09 (4H, m), 6.80 (2H, d, J=8.5
Hz), 7.06 (2H, d, J=8.5 Hz), 7.15-7.31 (5H, m).
Reference Example 20
Ethyl 2-butyl-3-[4-[2-(butylamino)ethoxy]phenyl]propionate
[1553] In a similar manner to that described in Reference example
19, a reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-butylp- ropionate (500 mg), which is
the product of Reference example 6, butylaldehyde (0.15 ml), sodium
cyanoborohydride (107 mg) and acetic acid (one drop) and the
reaction mixture was treated to afford the title compound (390 mg)
as a yellow oil.
[1554] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 0.94 (3H, t, J=7.5 Hz), 1.17 (3H, t, J=7.0 Hz),
1.22-1.73 (10H, m), 2.52-3.00 (5H, m), 3.20-3.28 (2H, m), 3.99-4.20
(4H, m), 6.84 (2H, d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz).
Reference Example 21
Ethyl 3-[4-(3-aminopropoxy)phenyl]-2-butylpropionate
[1555] (a)
2-butyl-3-[4-[3-(tetrahydropyran-2-yloxy)propoxy]phenyl]propion-
ate
[1556] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
2-(4-hydroxybenzyl)caproate (3.02 g),
2-(3-bromopropoxy)-tetrahydropyran (3.23 g)and potassium carbonate
(5.00 g) and the reaction mixture was treated to afford the desired
compound (4.42 g) as a colorless oil.
[1557] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.22-1.35 (4H, m), 1.47-1.88
(8H, m), 2.06 (2H, quintuplet, J=6.0 Hz), 2.52-2.63 (1H, m), 2.67
(1H, dd, J=6.5, 13.5 Hz), 2.85 (1H, dd, J=8.5, 13.5 Hz), 3.46-3.61
(2H, m), 3.80-3.97 (2H, m), 4.01-4.10 (4H, m), 4.60 (1H, t, J=3.5
Hz), 6.80 (2H, d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz).
[1558] (b) Ethyl
2-butyl-3-[4-(3-hydroxypropoxy)phenyl]propionate
[1559] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-butyl-3-[4-[3-(tetrahydropyran-2-y-
loxy)propoxy]phenyl]propionate (4.42 g) and p-toluensulfonic acid
monohydrate (2.57 g) and the reaction mixture was treated to afford
the desired compound (3.02 g) as a colorless oil.
[1560] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm
0.87(3H,t,J=7.0Hz), 1.16(3H,t,J=7.0Hz), 1.22-1.35 (4H, m),
1.40-1.70 (2H, m), 1.77 (1H, t, J=5.5 Hz), 2.03 (2H, quintuplet,
J=5.5 Hz), 2.53-2.65 (1H, m), 2.68 (1H, dd, J=6.5, 13.5 Hz), 2.86
(1H, dd, J=8.5, 13.5 Hz), 3.86 (2H, q, J=5.5 Hz), 4.02-4.17 (4H,
m), 6.81 (2H, d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz).
[1561] (c) Ethyl
2-butyl-3-[4-(3-methansulfonyloxypropoxy)phenyl]propionat- e
[1562] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
2-butyl-3-[4-(3-hydroxypropoxy)pheny- l]propionate (3.02 g),
triethylamine (2.05 ml) and methanesulfonyl chloride (0.83 ml) and
the reaction mixture was treated to afford the desired compound
(3.49 g) as a colorless oil.
[1563] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.34 (4H, m), 1.40-1.70
(2H, m), 2.21 (2H, quintuplet, J=6.0 Hz), 2.52-2.64 (1H, m), 2.68
(1H, dd, J=6.5, 13.5 Hz), 2.86 (1H, dd, J=8.5, 13.5 Hz), 2.98 (3H,
s), 4.02-4.11 (4H, m), 4.44 (2H, t, J=6.0 Hz), 6.80 (2H, d, J=8.5
Hz), 7.07 (2H, d, J=8.5 Hz).
[1564] (d) Ethyl 3-[4-(3-azidopropoxy)phenyl]-2-butylpropionate
[1565] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-butyl-3-[4-(3-methanesulfonyloxypr- opoxy)phenyl]propionate (2.98
g) and sodium azide (1.50 g) and the reaction mixture was treated
to afford the desired compound (2.45 g) as a colorless oil.
[1566] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm
0.87(3H,t,J=7.0Hz), 1.16(3H,t,J=7.0Hz), 1.20-1.34 (4H, m),
1.40-1.70 (2H, m), 2.03 (2H, quintuplet, J=6.5 Hz), 2.51-2.63 (1H,
m), 2.67 (1H, dd, J=6.5, 13.5 Hz), 2.85 (1H, dd, J=8.5, 13.5 Hz),
3.51 (2H, t, J=6.5 Hz), 4.02 (2H, t, J=6.5 Hz), 4.05 (2H, q, J=7.0
Hz), 6.80 (2H, d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz).
[1567] (e) Ethyl 3-[4-(3-aminopropoxy)phenyl]-2-butylpropionate
[1568] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(3-azidopropoxy)phenyl]-2-butyl- propionate (2.45 g) and
palladium on carbon (5%, 250 mg) and the reaction mixture was
treated to afford the desired compound (1.62 g) as a colorless
oil.
[1569] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=6.5 Hz), 1.16 (3H, t, J=7.0 Hz), 1.22-1.34 (4H, m), 1.40-1.70
(2H, m), 1.80-2.10 (2H, m), 2.52-2.94 (6H, m), 4.00-4.11 (4H, m),
6.80 (2H, d, J=8.5 Hz), 7.06 (2H, d, J=8.5 Hz).
Reference Example 22
Ethyl 2-butyl-3-[4-(3-methylaminopropoxy)phenyl]propionate
[1570] A solution of methylamine in methanol (40%, 5.0 ml) was
added to a solution of ethyl
2-butyl-3-[4-(3-methansulfonyloxypropoxy)phenyl]propion- ate (500
mg), which is the product of Reference example 21(c) in toluene (10
ml). The mixture was stirred at 90.degree. C. for 2 days. The
reaction mixture was concentrated under reduced pressure. The
residue was partitioned between ethyl acetate and water and the
layers were separated. The ethyl acetate solution was dried over
anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was purified via chromatography on a silica
gel column using dichloromethane/methanol=- 5/1 as the eluant to
afford the title compound (389 mg) as a pale yellow oil.
[1571] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.87 (3H, t,
J=6.5 Hz), 1.15 (l.5H, t, J=7.0 Hz), 1.16 (1.5H, t, J=7.0 Hz),
1.22-1.35 (4H, m), 1.42-1.70 (2H, m), 1.92-2.02 (1H, m), 2.17-2.27
(1H, m), 2.52-3.09 (8H, m), 3.92-4.10 (4H, m), 6.73-6.81 (2H, m),
7.00-7.09 (2H, m).
Reference Example 23
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-propylpropionate
[1572] (a) Diethyl 2-(4-benzyloxybenzyl)-2-propylmalonate
[1573] In a similar manner to that described in Reference example
2(a), a reaction was carried out using diethyl 2-propylmalonate
(5.00 g), 4-benzyloxybenzyl chloride (6.32 g) and sodium hydride
(55% suspension in oil, 1.13 g) and the reaction mixture was
treated to afford the desired compound (9.80 g) as a colorless
oil.
[1574] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.92 (3H, t,
J=7.0 Hz), 1.23 (6H, t, J=7.0 Hz), 1.23-1.38 (2H, m), 1.71-1.80
(2H, m), 3.18 (2H, s), 4.08-4.21 (4H, m), 5.02 (2H, s), 6.86 (2H,
d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz), 7.30-7.48 (5H, m).
[1575] (b) 3-(4-benzyloxyphenyl)-2-propylpropionic acid
[1576] In a similar manner to that described in Reference example
2(b), a reaction was carried out using diethyl
2-(4-benzyloxybenzyl)-2-propylmalo- nate (9.85 g), which is the
product of Reference example 23(a), and potassium hydroxide (5.25
g) and the reaction mixture was treated to afford the desired
compound (3.96 g) as brown crystals.
[1577] mp 83-85.degree. C.
[1578] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, t,
J=7.0 Hz), 1.24-1.70 (4H, m), 2.59-3.00 (3H, m), 5.03 (2H, s), 6.90
(2H, d, J=8.5 Hz), 7.10 (2H, d, J=8.5 Hz), 7.21-7.48 (5H, m).
[1579] (c) Ethyl 3-(4-benzyloxyphenyl)-2-propylpropionate(c)
[1580] 1,8-Diazabicyclo[5.4.0]undec-7-ene (2.34 ml) and ethyl
iodide (1.57 ml) were added to a solution of
3-(4-benzyloxyphenyl)-2-propylpropionic acid (3.90 g), which is the
product of Reference example 23(b), in N,N-dimethylformamide (40
ml). The reaction mixture was stirred at 60.degree. C. for 4 hours.
The reaction mixture was partitioned between ethyl acetate and
water and the layers were separated. The ethyl acetate layer was
dried over anhydrous magnesium sulfate and concentrated under
reduced pressure. The residue was purified via chromatography on a
silica gel column using hexane/ethyl acetate=5/1-4/1 as the eluant
to afford the desired compound (4.00 g) as a colorless oil.
[1581] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.14 (3H, t, J=7.0 Hz), 1.20-1.70 (4H, m), 2.56-2.62
(1H, m), 2.68 (1H, dd, J=6.0, 13.0 Hz), 2.86 (1H, dd, J=8.0, 13.0
Hz), 4.05 (2H, q, J=7.0 Hz), 5.03 (2H, s), 6.88 (2H, d, J=8.5 Hz),
7.07 (2H, d, J=8.5 Hz), 7.28-7.47 (5H, m).
[1582] (d) Ethyl 3-(4-hydroxyphenyl)-2-propylpropionate
[1583] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-propylpropio- nate (4.00 g) and palladium
on carbon (5%, 0.40 g) and the reaction mixture was treated to
afford the desired compound (3.10 g) as a syrup.
[1584] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.89 (3H, t,
J=7.0 Hz), 1.15 (3H, t, J=7.0 Hz), 1.21-1.70 (4H, m), 2.53-2.72
(2H, m), 2.84 (1H, dd, J=8.5, 13.0 Hz), 4.05 (2H, q, J=7.0 Hz),
4.75-4.82 (1H, m), 6.72 (2H, d, J=8.5 Hz), 7.02 (2H, d, J=8.5
Hz).
[1585] (e) Ethyl
3-[4-(2-t-butoxycarbonylaminoeyhoxy)phenyl]-2-propylpropi-
onate
[1586] In a similar manner to that described in Example 122. a
reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-propylpropionate (1.65 g), which is the
product of Reference example 23(d), t-butyl 2-hydroxyethylcarbamate
(5.63 g) triphenylphophine (9.16 g) and diethyl azodicarboxylate
(6.14 ml) and the reaction mixture was treated to afford the
desired compound (2.22 g) as a colorless oil.
[1587] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.88 (3H, t,
J=7.0 Hz), 1.16 (3H, t, J=7.0 Hz), 1.20-1.70 (4H, m), 1.45 (9H, s),
2.55-2.71 (2H, m), 2.86 (1H, dd, J=8.0, 13.0 Hz), 3.51 (2H, q,
J=5.0 Hz), 3.90-4.15 (4H, m), 4.93-5.03 (1H, m), 6.79 (2H, d, J=8.5
Hz), 7.07 (2H, d, J=8.5 Hz).
Reference Example 24
3-[4-[2-(4'-Methoxymethoxy-3',5'-dimethylbiphenyl-4-carbonylamino)ethoxy]p-
henyl]-2-phenoxypropionic acid
[1588] (a) Ethyl
3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-
carbonylamino)ethoxy]phenyl]-2-phenoxypropionate
[1589] In a similar manner to that described in Example 5, a
reaction was carried out using ethyl
3-[4-(2-aminoethoxy)phenyl]-2-phenoxypropionate (2.07 g), which is
the product of Reference example 4,
4'-methoxymethoxy-3',5'-dimethylbiphenyl-4-carboxylic acid (1.50
g), which is the product of reference example 17(b), and
carbonyldiimidazole (1.10 g) and the reaction mixture was treated
to afford the desired compound (720 mg) as a colorless oil.
[1590] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 2.36 (6H, s), 3.18 (1H, d, J=5.5 Hz), 3.19 (1H, d, J=7.5
Hz), 3.64 (3H, s), 3.88 (2H, q, J=5.0 Hz), 4.15 (2H, t, J=5.0 Hz),
4.18 (2H, q, J=7.0 Hz), 4.74 (1H, dd, J=5.5, 7.5 Hz), 5.00 (2H, s),
6.61 (1H, brt), 6.83 (2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz),
6.94 (1H, t, J=7.5 Hz), 7.20-7.30 (6H, m), 7.60 (2H, d, J=8.5 Hz),
7.82 (2H, d, J=8.5 Hz).
[1591] (b) 3-[4-[2-(4'-Methoxymethoxy-3',5'-dimethylbiphenyl-4-
carbonylamino)ethoxy]phenyl]-2-phenoxypropionic acid
[1592] In a similar manner to that described in Example 2, a
reaction was carried out using ethyl
3-[4-[2-(4'-methoxymethoxy-3',5'-dimethylbiphenyl-
-4-carbonylamino)ethoxy]phenyl]-2-phenoxypropionate (720 mg), which
is the product of Reference example 24(a) and aqueous sodium
hydroxide (1N, 2.40 ml) and the reaction mixture was treated to
afford the title compound (520 mg) as a white powder.
[1593] mp 142-143.degree. C.
[1594] H-NMR (270 MHz, deuterated methanol): .delta. ppm 2.35 (6H,
s), 3.14 (1H, d, J=7.5 Hz), 3.16 (1H, d, J=4.5 Hz), 3.60 (3H, s),
3.77 (2H, q, J=5.5 Hz), 4.16 (2H, t, J=5.5 Hz), 4.86 (1H, dd,
J=4.5, 7.5 Hz), 5.00 (2H, s), 6.83 (2H, d, J=7.5 Hz), 6.86-6.93
(1H, m), 6.90 (2H, d, J=8.5 Hz), 7.19 (2H, d, J=7.5 Hz), 7.24 (2H,
d, J=8.5 Hz), 7.33 (2H, s), 7.65 (2H, d, J=8.5 Hz), 7.86 (2H, d,
J=8.5 Hz), 8.68 (1H, brt).
Reference Example 25
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-isopropylphenoxy)pr-
opionate
[1595] Potassium carbonate (23.5 g) was added to a solution of
ethyl 3-(4-hydroxyphenyl)-2-(4-iospropylphenoxy)propionate (18.2
g), which is the product of Reference example 5(d), in a mixture of
N,N-dimethylformamide (200 ml) and toluene (100 ml) at ambient
temperature. To this suspension a solution of t-butyl
2-methanesulfonyloxyethylcarbamate (12.2 g) in toluene (40 ml) was
added dropwise at 70.degree. C. and the mixture was stirred at the
same temperature for 2 hours. Further, to this reaction mixture a
solution of t-butyl 2-methanesulfonyloxyethylcarbamate (12.2 g) in
a mixture of N,N-dimethylformamide (10 ml) and toluene (40 ml) was
added and the the mixture was stirred at 70.degree. C. overnight.
The reaction mixture was partitioned between ethyl acetate and
water. The ethyl acetate layer was washed with saturated aqueous
sodium chloride solution and dried over anhydrous magnesium sulfate
and concentrated under reduced pressure. The residue was purified
via chromatography on a silica gel column using toluene/ethyl
acetate=20/1-hexane/ethyl acetate=3/1 as the eluant to afford the
desired compound (18.7 g) as a colorless oil.
[1596] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 1.45 (9H, s), 2.82 (1H, septet, J=7.0 Hz), 3.16 (1H, d,
J=5.0 Hz), 3.18 (1H, d, J=7.5 Hz), 3.52 (2H, q, J=5.0 Hz), 3.99
(2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.69 (1H, dd, J=5.0, 7.5
Hz), 4.97 (1H, brt), 6.76 (2H, d, J=8.5 Hz), 6.81 (2H, d, J=8.5
Hz), 7.08 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz).
Reference Example 26
6-(4-Methoxyphenyl)nicotinic acid
[1597] In a similar manner to that described in Example 2, a
reaction was carried out using methyl 6-(4-methoxyphenyl)nicotinate
(3.95 g) and aqueous sodium hydroxide solution (1N, 32.5 ml) and
the reaction mixture was treated to afford the title compound (2.63
g) as colorless crystals.
[1598] mp 252-253.degree. C.
[1599] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.84 (3H, s),
7.08 (2H, d, J=9.0 Hz), 8.04 (1H, d, J=8.5 Hz), 8.14 (2H, d, J=9.0
Hz), 8.27 (1H, dd, J=2.5, 8.5 Hz), 9.09 (1H, d, J=2.5 Hz).
Reference Example 27
6-(4-Fluorophenyl)nicotinic acid
[1600] In a similar manner to that described in Example 2, a
reaction was carried out using methyl 6-(4-fluorophenyl)nicotinate
(390 mg) and aqueous sodium hydroxide solution (1N, 5.00 ml) and
the reaction mixture was treated to afford the title compound (345
mg) as a pale yellow solid.
[1601] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 7.35 (2H, t,
J=8.5 Hz), 8.11 (1H, d, J=8.5 Hz), 8.15-8.29 (2H, m), 8.32 (1H, dd,
J=2.0, 8.5 Hz), 9.13 (1H, d, J=2.0 Hz).
Reference Example 28
6-(2,2,3,3-tetrafluoropropoxy)nicotinic acid
[1602] In a similar manner to that described in Reference example
1(c), a reaction was carried out using 2,2,3,3-tetrafluoropropanol
(5.23 ml), sodium hydride (55% suspension in oil, 1.91 g) and
methyl 6-chloronicotinate (5.00 g) and treated to afford crude
methyl 6-(2,2,3,3-tetrafluoropropoxy)nicotinate (5.42 g) as a
colorless oil. In a similar manner to that described in Example 2,
a reaction was carried out using the crude product described above
(2.70 g) and aqueous sodium hydroxide solution (2N, 15 ml) and the
reaction mixture was treated to afford crude title compound (1.60
g). This product was used in Example 102 and Example 150 without
further purification.
Reference Example 29
2-Trimethylsilylethyl
(S)-2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-yl--
benzoylamino)ethoxy]phenyl]propionate
[1603] (a)
(S)-4-benzyl-3-[(4-isopropylphenoxy)acetyl]oxazolidine-2-one
[1604] Oxalyl chloride (16.8 ml) and N,N-dimethylformamide (three
drops) were added to a solution of 4-isopropylphenoxyacetic acid
(15.0 g) in dichloromethane (75 ml) at ambient temperature. The
reaction mixture was stirred for 1.5 hours. The reaction mixture
was concentrated at reduced pressure and residual reagents were
azeotropically evaporated off with toluene. The residue was dried
under reduced pressure.
[1605] A solution of n-butyl lithium in hexane (1.61N, 48.0 ml) was
added dropwise to a solution of (S)-4-benzyloxazolidine-2-one (12.4
g) in tetrahydrofuran (150 ml) at -78.degree. C. and the mixture
was stirred at the same temperature for 30 minutes. To this
solution a solution of 4-isopropylphenoxyacetyl chloride, which had
been obtained above, in tetrahydrofuran (100 ml) was added at
-78.degree. C. The mixture was stirred at 0.degree. C. for 1 hour.
The reaction mixture was partitioned between ethyl acetate and
water. The ethyl acetate layer was washed with aqueous hydrogen
chloride solution (1N), saturated aqueous sodium hydrogencarbonate
solution and saturated aqueous sodium chloride solution. The ethyl
acetate solution was dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was crystallized
from a mixture of hexane/ethyl acetate=6/1 to afford the desired
compound (20.9 g) as colorless crystals.
[1606] mp 104.5-105.degree. C.
[1607] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.23 (6H, d,
J=7.0 Hz), 2.79-2.92 (2H, m), 3.36 (1H, dd, J=3.0, 13.5 Hz),
4.24-4.37 (2H, m), 4.68-4.78 (1H, m), 5.22 (2H, s), 6.91 (2H, d,
J=8.5 Hz), 7.13-7.38 (7H, m).
[1608] (b)
(S)-4-benzyl-3-[(2S,3R)-3-(4-benzyloxyphenyl)-3-hydroxy-2-(4-is-
opropylphenoxy)propionyl]oxazolidine-2-one
[1609] A solution of dibutylboron triflate in dichloromethane (1M,
67.9 ml) and triethylamine (10.2 ml) was added to a solution of
(S)4-benzyl-3-[(4-isopropylphenoxy)acetyl]oxazolidine-2-one (20.0
g) in dichloromethane (150 ml) at 0.degree. C. The mixture was
stirred at the same temperature for 1 hour. To the reaction mixture
a solution of 4-benzyloxybenzaldehyde (13.2 g) in dichloromethane
(20 ml) was added dropwise at -78.degree. C. and then stirred at
the same temperature for 40 minutes. The reaction mixture was
further stirred at 0.degree. C. for 1 hour. At the end of this time
a mixture of saturated aqueous sodium chloride
solution/methanol=1/1 (50 ml) and aqueous hydrogen peroxide
solution (31%)/methanol=2/1 (150 ml) was added to the reaction
mixture and stirred for 1 hour. The mixture was concentrated under
reduced pressure. The residue was partitioned between ethyl acetate
and water and the layers were separated. The ethyl acetate layer
was washed with aqueous hydrogen chloride solution (1N), saturated
aqueous sodium hydrogencarbonate solution and saturated aqueous
sodium chloride solution and dried over anhydrous magnesium sulfate
and concentrated under reduced pressure. The residue was purified
via chromatography on a silica gel column using hexane/ethyl
acetate=3/1-1/1 as the eluant to afford the desired compound (25.7
g) as a mass of foam.
[1610] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (6H, d,
J=7.0 Hz), 2.73 (1H, dd, J=9.5, 13.5 Hz), 2.85 (1H, septet J=7.0
Hz), 3.07 (1H, dd, J=3.0, 13.5 Hz), 3.58 (1H, t, J=8.5 Hz), 3.97
(1H, d, J=9.0 Hz), 4.23-4.29 (1H, m), 5.04 (2H, s), 5.09 (1H, d,
J=5.5 Hz), 6.18 (1H, d, J=5.5 Hz), 6.91 (2H, d, J=8.5 Hz), 6.94
(2H, d, J=8.5 Hz), 7.05-7.10 (2H, m), 7.14 (2H, d, J=8.5 Hz),
7.23-7.44 (10H, m).
[1611] (c)
(S)-4-benzyl-3-[(2S,3R)-3-hydroxy-3-(4-hydroxyphenyl)-2-(4-isop-
ropylphenoxy)propionyl]oxazolidine-2-one
[1612] In a similar manner to that described in Reference example
1(d), a reaction was carried out using
(S)-4-benzyl-3-[(2S,3R)-3-(4-benzyloxyphen-
yl)-3-hydroxy-2-(4-isopropylphenoxy)propionyl]oxazolidine-2-one
(25.0 g), which is the product of Reference example 29(b) and
palladium on carbon (5%, 2.50 g) and the reaction mixture was
treated to afford the desired compound (19.1 g) as a mass of
foam.
[1613] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=7.0 Hz), 2.76 (1H, dd, J=9.0, 13.5 Hz), 2.85 (1H, septet, J=7.0
Hz), 3.07 (1H, dd, J=3.0, 13.5 Hz), 3.17 (1H, d, J=4.5 Hz), 3.73
(1H, t, J=8.5 Hz), 4.04 (1H, d, J=8.5 Hz), 4.25-4.35 (1H, m), 5.07
(1H, t, J=5.0 Hz), 5.52 (1H, s), 6.18 (1H, d, J=5.5 Hz), 6.78 (2H,
d, J=8.5 Hz), 6.92 (2H, d, J=8.5 Hz), 7.02-7.12 (2H, m), 7.14 (2H,
d, J=8.5 Hz), 7.22-7.29 (3H, m), 7.32 (2H, d, J=8.5 Hz).
[1614] (d)
(S)-4-benzyl-3-[(S)-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)p-
ropionyl]oxazolidine-2-one
[1615] Triethylsilane (30.2 ml) was added to a solution of
(S)-4-benzyl-3-[(2S,3R)-3-hydroxy-3-(4-hydroxyphenyl)-2-(4-isopropylpheno-
xy)propionyl]oxazolidine-2-one (18.0 g), which is the product of
Reference example 29(c), in trifluoroacetic acid (150 ml) at
ambient temperature. The mixture was stirred for 18 hours. The
reaction mixture was concentrated under reduced pressure. The
residue was partitioned between ethyl acetate and water and the
layers were separated. The ethyl acetate layer was washed with
saturated aqueous sodium hydrogencarbonate solution, aqueous
hydrogen chloride solution (1N) and saturated aqueous sodium
chloride solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=3/1 as the eluant to afford the desired compound (10.7 g)
as colorless crystals.
[1616] mp 142-143.degree. C.
[1617] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 2.75-2.88 (2H, m), 3.10-3.21 (3H, m), 4.03 (1H, t, J=8.0
Hz), 4.17 (1H, d, J=9.0 Hz), 4.48-4.55 (1H, m), 4.89 (1H, s), 6.08
(1H, dd, J=5.5, 8.0 Hz), 6.74 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5
Hz), 7.05-7.16 (4H, m), 7.21-7.36 (5H, m).
[1618] (e) 2-Trimethylsilylethyl
(S)-3-(4-hydroxyphenyl)-2-(4-isopropylphe- noxy)propionate
[1619] A mixture of aqueous lithium hydroxide solution (1N, 57.0
ml) and aqueous hydrogen peroxide solution (31%, 6.34 ml) was added
dropwise to a suspension of
(S)-4-benzyl-3-[(S)-3-(4-hydroxyphenyl)-2-(4-isopropylpheno-
xy)propionyl]oxazolidine-2-one (10.6 g), which is the product of
Reference example 29(d), in a mixture of methanol (140 ml) and
tetrahydrofuran (15 ml). After the mixture was stirred at ambient
temperature for 6 hours, a solution of sodium dithionite (10.1 g)
in water (50 ml) was added to the reaction mixture and the mixture
was stirred for 1 hour. The reaction mixture was concentrated under
reduced pressure. Aqueous sodium hydroxide solution (1N) was added
to the residue to make it basic. The solution was washed with
dichloromethane and partitioned between aqueous hydrogen chloride
solution and ethyl acetate. The ethyl acetate layer was separated
and dried over anhydrous magnesium sulfate and then concentrated
under reduced pressure. The residue was crystallized from hexane to
afford (S)-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propionic acid
(6.00 g) as a white powder. Oxalyl chloride (5.50 ml) and
N,N-dimethylformamide (5 drops) were added to a suspension of this
carboxylic acid (4.43 g) in dichloromethane (100 ml) at ambient
temperature. The mixture was stirred for 1 hour. At the end of this
time the reaction mixture was concentrated under reduced pressure.
The residue was azeotropically distilled off using toluene to
remove excess reagent. 2-Trimethylsilylethanol (9.06 ml) was added
to a solution of the residue in dichloromethane (50 ml). This
mixture was stirred at ambient temperature for 15 hours.
Triethylamine (4.40 ml) and 4-N,N-dimethylaminopyridine (155 mg)
were added to the mixture. This mixture was stirred at ambient
temperature for 2 hours. The reaction mixture was concentrated
under reduced pressure. The residue was partitioned between ethyl
acetate and water and the layers were separated. The ethyl acetate
layer was washed with saturated aqueous sodium chloride solution
and dried over anhydrous magnesium sulfate and concentrated under
reduced pressure. The residue was purified via chromatography on a
silica gel column using hexane/ethyl acetate=5/1-4/1 as the eluant
to afford the desired compound (5.30 g) as a pale yellow oil.
[1620] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.00 (9H, s),
0.92 (2H, t, J=8.5 Hz), 1.18 (6H, d, J=7.0 Hz), 2.81 (1H, septet,
J=7.0 Hz), 3.10-3.17 (2H, m), 4.19 (2H, t, J=8.5 Hz), 4.66 (1H, dd,
J=6.0, 7.0 Hz), 6.73 (2H, d, J=8.5 Hz), 6.74 (2H, d, J=8.5 Hz),
7.07 (2H, d, J=8.5 Hz), 7.15 (2H, d, J=8.5 Hz).
[1621] (f) 2-Trimethylsilylethyl
(S)-3-[4-(2-t-butoxycarbonylaminoethoxy)p-
henyl]-2-(4-isopropylphenoxy)propionate
[1622] In a similar manner to that described in Reference example
25, a reaction was carried out using 2-trimethylsilylethyl
(S)-3-(4-hydroxyphenyl)-2-(4-isopropyl-phenoxy)propionate (4.80 g),
which is the product of Reference example 29(e), t-butyl
2-methanesulfonyloxyethylcarbamate (7.17 g) and potassium carbonate
(8.28 g) and the reaction mixture was treated to afford the desired
compound (5.94 g) as a colorless oil.
[1623] [.alpha.].sub.D.sup.25-6.0.degree. (c=0.9, chloroform)
[1624] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 0.00 (9H, s),
0.91 (2H, t, J=8.5 Hz), 1.17 (6H, d, J=7.0 Hz), 1.45 (9H, s), 2.81
(1H, septet, J=7.0 Hz), 3.08-3.18 (2H, m), 3.45-3.54 (2H, m),
3.93-4.00 (2H, m), 4.10-4.25 (2H, m), 4.65 (1H, dd, J=5.5, 7.5 Hz),
4.93-5.00 (1H, m), 6.74 (2H, d, J=8.5 Hz), 6.80 (2H, d, J=8.5 Hz),
7.06 (2H, d, J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz).
[1625] (g) 2-Trimethylsilylethyl
(S)-2-(4-isopropylphenoxy)-3-[4-[2-(4-pyr-
idine-2-yl-benzoylamino)ethoxy]phenyl]propionate
[1626] In a similar manner to that described in Example 73, a
reaction was carried out using 2-trimethylsilylethyl
(S)-3-[4-(2-t-butoxycarbonylamino-
ethoxy)phenyl]-2-(4-isopropylphenoxy)propionate (0.95 g),
4-pyridine-2-ylbenzoic acid (382 mg), diethyl cyanophosphonate
(0.29 ml) and triethylamine (0.53 ml) and the reaction mixture was
treated to afford the title compound (0.62 g) as a colorless
oil.
[1627] [.alpha.].sub.D.sup.25-3.0.degree. (c=0.7, chloroform)
[1628] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 0.05 (9H, s),
0.97 (2H, t, J=8.5 Hz), 1.15-1.23 (6H, m), 2.86 (1H, septet, J=7.0
Hz), 3.14-3.23 (2H, m), 3.85-3.95 (2H, m), 4.15-4.27 (4H, m), 4.70
(1H, dd, J=5.5, 7.5 Hz), 6.64-6.74 (1H, m), 6.79 (2H, d, J=8.5 Hz),
6.90 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz), 7.24-7.34 (3H, m),
7.76-7.84 (2H, m), 7.93 (2H, d, J=8.5 Hz), 8.11 (2H, d, J=8.5 Hz),
8.76 (1H, d, J=5.0 Hz).
Reference Example 30
2-Trimethylsilylethyl
(R)-2-(4-isopropylphenoxy)-3-[4-[2-(4-pyridine-2-yl--
benzoylamino)ethoxy]phenyl]propionate
[1629] (a)
(R)-4-benzyl-3-[(4-isopropylphenoxy)acetyl]oxazolidine-2-one
[1630] In a similar manner to that described in Reference example
29(a), a reaction was carried out using 4-isopropylphenoxyacetic
acid (14.1 g), oxalyl chloride (15.8 ml),
(R)-4-benzyloxazolidine-2-one (11.7 g) and a solution of n-butyl
lithium in hexane (1.61N, 45.0 ml) and the reaction mixture was
treated to afford the desired compound (18.6 g) as colorless
crystals.
[1631] mp 104.5-105.degree..5 C.
[1632] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 1.23 (6H, d,
J=7.0 Hz), 2.80-2.91 (2H, m), 3.36 (1H, dd, J=3.0, 13.5 Hz), 4.28
(1H, dd, J=3.0, 9.0 Hz), 4.33 (1H, dd, J=8.0, 9.0 Hz), 4.68-4.78
(1H, m), 5.22 (2H, s), 6.91 (2H, d, J=8.5 Hz), 7.14-7.38 (7H,
m).
[1633] (b)
(R)-4-benzyl-3-[(2R,3R)-3-(4-benzyloxyphenyl)-3-hydroxy-2-(4-is-
opropylphenoxy)propionyl]oxazolidine-2-one
[1634] In a similar manner to that described in Reference example
29(b), a reaction was carried out using
(R)-4-benzyl-3-[(4-isopropylphenoxy)acetyl- ]oxazolidine-2-one
(10.0 g), which is the product of Reference example 30(a), solution
of dibutylboron triflate in dichloromethane (1M, 34.0 ml),
triethylamine (5.11 ml) and 4-benzyloxybenzaldehyde (6.60 g) and
the reaction mixture was treated to afford the desired compound
(12.1 g) as a mass of foam.
[1635] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=7.0 Hz), 2.73 (1H, dd, J=9.0, 13.5 Hz), 2.85 (1H, septet, J=7.0
Hz), 3.02-3.12 (1H, m), 3.53-3.63 (1H, m), 3.93-4.01 (1H, m),
4.21-4.32 (1H, m), 5.02-5.12 (3H, m), 6.18 (1H, d, J=6.0 Hz),
6.88-7.46 (18H, m).
[1636] (c)
(R)-4-benzyl-3-[(2R,3S)-3-hydroxy-3-(4-hydroxyphenyl)-2-(4-isop-
ropylphenoxy)propionyl]oxazolidine-2-one
[1637] In a similar manner to that described in Reference example
1(d), a reaction was carried out using
(R)-4-benzyl-3-[(2R,3S)-3-(4-benzyloxyphen-
yl)-3-hydroxy-2-(4-isopropylphenoxy)propionyl]oxazolidine-2-one
(9.00 g), which is the product of Reference example 30(b) and
palladium on carbon (5%, 1.80 g) and the reaction mixture was
treated to afford the desired compound (7.48 g) as a mass of
foam.
[1638] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (6H, d,
J=7.0 Hz), 2.75 (1H, dd, J=9.0, 13.5 Hz), 2.85 (1H, septet, J=7.0
Hz), 3.05-3.14 (2H, m), 3.70-3.79 (1H, m), 4.01-4.09 (1H, m),
4.26-4.35 (1H, m), 5.04-5.12 (1H, m), 5.34 (1H, brs), 6.18 (1H, d,
J=6.0 Hz), 6.80 (2H, d, J=8.5 Hz), 6.92 (2H, d, J=8.5 Hz),
7.04-7.37 (9H, m).
[1639] (d)
(R)-4-benzyl-3-[(R)-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)p-
ropionyl]oxazolidine-2-one
[1640] In a similar manner to that described in Reference example
29(d), a reaction was carried out using
(R)-4-benzyl-3-[(2R,3S)-3-hydroxy-3-(4-hyd-
roxyxyphenyl)-2-(4-isopropylphenoxy)propionyl]oxazolidine-2-one
(7.00 g), which is the product of Reference example 30(c), and
triethylsilane (18.8 ml) and the reaction mixture was treated to
afford the desired compound (4.89 g) as colorless crystals.
[1641] mp 147-148.degree. C.
[1642] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (6H, d,
J=7.0 Hz), 2.71-2.88 (2H, m), 3.09-3.22 (3H, m), 3.97-4.07 (1H, m),
4.15 (1H, dd, J=2.5, 7.0 Hz), 4.47-4.57 (1H, m), 4.88 (1H, s), 6.08
(1H, d, J=5.5, 8.0 Hz), 6.75 (2H, d, J=8.5 Hz), 6.83 (2H, d, J=8.5
Hz), 7.05-7.30 (9H, m).
[1643] (e) 2-Trimethylsilylethyl
(R)-3-(4-hydroxyphenyl)-2-(4-isopropylphe- noxy)propionate
[1644] In a similar manner to that described in Reference example
29(e), a reaction was carried out using
(R)-4-benzyl-3-[(R)-3-(4-hydroxyphenyl)-2--
(4-isopropylphenoxy)propionyl]oxazolidine-2-one (3.78 g), which is
the product of Reference example 30(d), aqueous lithium hydroxide
solution (1N, 20.6 ml) and aqueous hydrogen peroxide solution (31%,
2.26 ml) and the reaction mixture was treated to afford
(R)-3-(4-hydroxyphenyl)-2-(4-i- sopropylphenoxy)propionic acid
(2.18 g) as a white powder. This acid (1.95 g) was reacted with
oxalyl chloride (2.73 ml) and 2-trimethylsilylethanol (4.66 ml) and
the reaction mixture was treated in a similar manner to that
described Reference example 29(e) to afford the desired compound
(2.26 g) as a colorless oil.
[1645] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.00 (9H, s),
0.92 (2H, t, J=8.5 Hz), 1.18 (6H, d, J=7.0 Hz), 2.81 (1H, septet,
J=7.0 Hz), 3.07-3.18 (2H, m), 4.11-4.25 (2H, m), 4.70 (1H, dd,
J=5.5, 7.0 Hz), 5.75 (1H, s), 6.72 (2H, d, J=8.5 Hz), 6.75 (2H, d,
J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz), 7.12 (2H, d, J=8.5 Hz).
[1646] (f) 2-Trimethylsilylethyl
(R)-3-[4-(2-t-butoxycarbonylaminoethoxy)p-
henyl]-2-(4-isopropylphenoxy)propionate
[1647] In a similar manner to that described in Reference example
25, a reaction was carried out using 2-trimethylsilylethyl
(R)-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propionate (221 mg),
which is the product of Reference example 30(e), t-butyl
2-methanesulfonyloxyethylcarbamate (330 mg) and potassium carbonate
(381 mg) and the reaction mixture was treated to afford the desired
compound (264 mg) as a colorless oil.
[1648] [.alpha.].sub.D.sup.25+6.8.degree. (c=0.9, chloroform)
[1649] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.00 (9H, s),
0.93 (2H, t, J=8.5 Hz), 1.19 (6H, d, J=7.0 Hz), 1.45 (9H, s), 2.82
(1H, septet, J=7.0 Hz), 3.10-3.20 (2H, m), 3.43-3.54 (2H, m), 3.98
(2H, t, J=5.0 Hz), 4.11-4.25 (2H, m), 4.66 (1H, dd, J=5.5, 7.0 Hz),
4.91-5.01 (1H, m), 6.75 (2H, d, J=8.5 Hz), 6.81 (2H, d, J=8.5 Hz),
7.08 (2H, d, J=8.5 Hz), 7.22 (2H, d, J=8.5 Hz).
[1650] (g) 2-Trimethylsilylethyl
(R)-2-(4-isopropylphenoxy)-3-[4-[2-(4-pyr-
idine-2-yl-benzoylamino)ethoxy]phenyl]propionate
[1651] In a similar manner to that described in Example 73, a
reaction was carried out using 2-trimethylsilylethyl
(R)-3-[4-(2-t-butoxycarbonylamino-
ethoxy)phenyl]-2-(4-isopropylphenoxy)propionate (356 mg),
4-pyridine-2-ylbenzoic acid (143 mg), diethyl cyanophosphonate
(0.11 ml) and triethylamine (0.10 ml) and the reaction mixture was
treated to afford the title compound (307 mg) as a colorless
oil.
[1652] [.alpha.].sub.D.sup.25+2.8.degree. (c=2.1, chloroform)
[1653] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. ppm 0.05 (9H, s),
0.97 (2H, t, J=8.5 Hz), 1.18-1.22 (6H, m), 2.85 (1H, septet, J=7.0
Hz), 3.15-3.23 (2H, m), 3.92 (2H, q, J=5.0 Hz), 4.15-4.30 (4H, m),
4.71 (1H, dd, J=5.5, 7.5 Hz), 6.64-6.74 (1H, m), 6.79 (2H, d, J=8.5
Hz), 6.89 (2H, d, J=8.5 Hz), 7.11 (2H, d, J=8.5 Hz), 7.26-7.34 (3H,
m), 7.78-7.83 (2H, m), 7.93 (2H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5
Hz), 8.75 (1H, d, J=5.0 Hz).
Reference Example 31
3-Trifluoromethylpyridine-6-ylbenzoic acid
[1654] (a) Methyl 3-trifluoromethylpyridine-6-ylbenzoate
[1655] 4-methoxycarbonylphenyl boronic acid (541 mg) and
2-chloro-5-trifluoromethylpyridine (718 mg) were added to a
suspension of bisbenzonitriledichloropalladium (119 mg) and
1,4-bisdiphenylphosphinobut- ane (131 mg) in toluene (10 ml) at
ambient temperature and then ethanol (5 ml) and saturated aqueous
sodium hydrogencarbonate solution (5 ml) were added to the mixture.
This mixture was heated at reflux for 5 hours at 100.degree. C. The
reaction mixture was partitioned between ethyl acetate and water.
The ethyl acetate layer was separated and washed with saturated
aqueous sodium chloride solution and dried over anhydrous magnesium
sulfate and concentrated under reduced pressure. To the residue
diisopropyl ether was added to afford the desired compound (841 mg)
as a white powder which include some impurity.
[1656] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.96 (3H, s),
7.91 (1H, d, J=8.5 Hz), 8.04 (1H, d, J=8.5 Hz), 8.12 (2H, d, J=8.5
Hz), 8.18 (2H, d, J=8.5 Hz), 8.98 (1H, s).
[1657] (b) 3-Trifluoromethylpyridine-6-ylbenzoic acid
[1658] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
3-trifluoromethylpyridine-6-ylbenzoate (791 mg) and aqueous sodium
hydroxide solution (1N, 5.60 ml) and the reaction mixture was
treated to afford the title compound (546 mg) which includes some
impurity and was used in example 106 without further
purification.
[1659] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 8.05 (1H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5 Hz), 8.29
(2H, d, J=8.5 Hz), 8.35 (1H, d, J=8.5 Hz), 9.10 (1H, s).
Reference Example 32
3-Nitropyridine-6-ylbenzoic acid
[1660] (a) Methyl 3-nitropyridine-6-ylbenzoate
[1661] In a similar manner to that described in Reference example
14(a), a reaction was carried out using 4-methoxycarbonylphenyl
boronic acid (3.24 g), 2-bromo-5-nitropyridine (4.75 g) and
tetrakis(triphenylphosphine)pall- adium (1.04 g) and treated to
afford the desired compound (3.67 g) as colorless crystals.
[1662] mp 197-199.degree. C.
[1663] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.97 (3H, s),
7.98 (1H, d, J=8.5 Hz), 8.19 (4H, s), 8.58 (1H, dd, J=2.5, 8.5 Hz),
9.53 (1H, d, J=2.5 Hz).
[1664] (b) 3-Nitropyridine-6-ylbenzoic acid
[1665] In a similar manner to that described in Example 2, a
reaction was carried out using methyl 3-nitropyridine-6-ylbenzoate
(545 mg), which is the product of Reference example 32(a), and
aqueous sodium hydroxide solution (1N, 3.16 ml) at 90.degree. C.
and the reaction mixture was treated to afford the title compound
(370 mg) as colorless crystals.
[1666] mp 262-264.degree. C.
[1667] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 8.11 (2H, d, J=8.0 Hz), 8.33 (2H, d, J=8.0 Hz), 8.36
(1H, d, J=8.0 Hz), 8.71 (1H, dd, J=2.0, 8.0 Hz), 9.48 (1H, d, J=2.0
Hz).
Reference Example 33
3-Methoxypyridine-6-ylbenzoic acid
[1668] (a) Methyl 3-aminopyridine-2-ylbenzoate
[1669] In a similar manner to that described in Reference example
1(d), a reaction was carried out using methyl
3-nitropyridine-6-ylbenzoate (1.13 g), which is the product of
Reference example 32(a) and palladium on carbon (221 mg) and
treated to afford the desired compound (738 mg) as colorless
crystals.
[1670] mp 188-189.degree. C.
[1671] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.83 (2H,
brs), 3.93 (3H, s), 7.06 (1H, dd, J=3.0, 8.5 Hz), 7.61 (1H, d,
J=8.5 Hz), 7.98 (2H, d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz), 8.20
(1H, d, J=3.0 Hz).
[1672] (b) Methyl 3-methoxypyridine-6-ylbenzoate
[1673] Concentrated sulfuric acid (0.14 ml) were added to a
suspension of methyl 3-aminopyridine-6-ylbenzoate (425 mg) and
sodium bromide (383 mg) in water at 0.degree. C. (10 ml) and then a
solution of sodium nitrite (295 mg) in water (1.5 ml) was added
dropwise to the mixture at 80.degree. C. The mixture was stirred at
the same temperature for 15 minutes. At the end of this time a
solution of amidosulfuric acid and concentrated sulfuric acid (0.21
ml) in water (1.60 ml) was added to the reaction mixture and this
mixture was stirred for 1.5 hours at 80.degree. C. and at ambient
temperature for 1 hour and then allowed to stand for 14 hours. The
pH of the reaction mixture was adjusted to pH 8 with aqueous sodium
hydroxide solution (1N). After addition of acetic anhydride (2.00
ml) to the solution, the mixture was stirred at ambient temperature
for 30 minutes. The reaction mixture was partitioned between ethyl
acetate and water and the ethyl acetate layer was separated and
washed with saturated aqueous sodium chloride solution and dried
over anhydrous magnesium sulfate. The ethyl acetate was distilled
off under reduced pressure to afford a mixture (457 mg) of methyl
5-acetoxypyridine-2-ylben- zoate and methyl
5-hydroxypyridine-2-ylbenzoate. In a similar manner to that
described in Example 2, a reaction was carried out using the
mixture obtained above and aqueous sodium hydroxide solution (1N,
2.10 ml) and the reaction mixture was treated to afford
5-hydroxypyridine-2-ylbenzoic acid as a white powder. In a similar
manner to that described in Reference example 1(c) a reaction was
carried out using 5-hydroxypyridine-2-ylbenzoic acid obtained
above, sodium hydride (55% suspension in oil, 174 mg) and methyl
iodide (0.35 ml) and the reaction mixture was treated to afford the
desired compound (429 mg) as colorless crystals
[1674] mp 130-132.degree. C.
[1675] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.93 (3H, s),
3.94 (3H, s), 7.30 (1H, dd, J=3.0, 9.0 Hz), 7.74 (1H, d, J=9.0 Hz),
8.02 (2H, d, J=8.5 Hz), 8.12 (2H, d, J=8.5 Hz), 8.43 (1H, d, J=3.0
Hz).
[1676] (c) 3-Methoxypyridine-6-ylbenzoic acid
[1677] In a similar manner to that described in Example 2, a
reaction was carried out using methyl
3-methoxypyridine-6-ylbenzoate (249 mg), which is the product of
Reference example 33(b), and aqueous sodium hydroxide solution (1N,
1.20 ml) and the reaction mixture was treated to afford the title
compound (206 mg) as colorless crystals.
[1678] mp 221-223.degree. C.
[1679] .sup.1H-NMR (270 MHz, CDCl.sub.3/deuterated methanol=3/1):
.delta. ppm 3.94 (3H, s), 7.35 (1H, dd, J=3.0, 8.5 Hz), 7.75 (1H,
d, J=8.5 Hz), 7.96 (2H, d, J=8.5 Hz), 8.13 (2H, d, J=8.5 Hz), 8.38
(1H, d, J=3.0 Hz).
Reference Example 34
3-Dimethylaminopyridine-6-ylbenzoic acid
[1680] (a) Methyl 3-dimethylaminopyridine-6-ylbenzoate
[1681] An aqueous solution of formaldehyde (35%, 3.20 ml) and
palladium on carbon (5%, 640 mg) was added to a suspension of
methyl 3-nitropyridine-6-ylbenzoate (519 mg) in a mixture of
methanol (25 ml) and 2-methoxyethanol (5 ml). The mixture was
stirred under an atmosphere of hydrogen at 50.degree. C. for 3
days. The catalyst was removed by filtration and the filtrate was
concentrated under reduced pressure. The residue was partitioned
between ethyl acetate and water. The ethyl acetate layer was
separated and washed with saturated aqueous sodium
hydrogencarbonate solution and saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was crystallized
from diisopropyl ether to afford the desired product (288 mg) as
colorless crystals.
[1682] mp 161-163.degree. C.
[1683] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 3.05 (6H, s),
3.93 (3H, s), 7.05 (1H, dd, J=3.0, 8.5 Hz), 7.66 (1H, d, J=8.5 Hz),
8.00 (2H, d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz), 8.24 (1H, d, J=3.0
Hz).
[1684] (b) 3-Dimethylaminopyridine-6-ylbenzoic acid
[1685] In a similar manner to that described in Example 2, a
reaction was carried out using-methyl
3-dimethylaminopyridine-6-ylbenzoate (277 mg), which is the product
of Reference example 34(a), and aqueous sodium hydroxide solution
(1N, 2.20 ml) and the reaction mixture was treated to afford the
title compound (237 mg)as colorless crystals.
[1686] mp 234-236.degree. C.
[1687] .sup.1H-NMR (270 MHz, deuterated dimethyl sulfoxide):
.delta. ppm 3.01 (6H, s), 7.18 (1H, dd, J=3.0, 9.0 Hz), 7.87 (1H,
d, J=9.0 Hz), 7.97 (2H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5 Hz), 8.23
(1H, d, J=3.0 Hz).
Reference Example 35
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-methylphenoxy)propi-
onate
[1688] (a) Ethyl
3-(4-benzyloxyphenyl)-2-methanesulfonyloxypropionate
[1689] Methanesulfonyl chloride (0.94 ml) was added to a solution
of ethyl 3-(4-benzyloxyphenyl)lactate (3.32 g), which is the
product of Reference example 1(b) , in anhydrous dichloromethane
(30 ml). To this mixture triethylamine (2.47 ml) was added dropwise
in an ice bath. The mixture was stirred at ambient temperature for
3 hours. The reaction mixture was concentrated under reduced
pressure. The residue was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and dried over
anhydrous magnesium sulfate and concentrated under reduced
pressure. The residue was crystallized from hexane to afford the
desired product (3.60 g) as colorless crystals.
[1690] mp 81-83.degree. C.
[1691] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.27 (3H, t,
J=7.0 Hz), 2.80 (3H, s), 3.02-3.29 (2H, m), 4.24 (2H, q, J=7.0 Hz),
5.05 (2H, s), 5.05-5.14 (1H, m), 6.93 (2H, d, J=8.5 Hz), 7.17 (2H,
d, J=8.5 Hz), 7.28-7.45 (5H, m).
[1692] (b) Ethyl
3-(4-benzyloxyphenyl)-2-(4-methylphenoxy)propionate
[1693] Potassium carbonate (8.09 g) was added to a solution of
ethyl 3-(4-benzyloxyphenyl)-2-methanesulfonyloxypropionate (11.1
g), which is the product of Reference example 35(a), and p-cresol
(2.85 g) in N,N-dimethylformamide (110 ml). This mixture was
stirred at 70.degree. C. for 16 hours. The reaction mixture was
partitioned between ethyl acetate and water and the layers were
separated. The ethyl acetate layer was dried over anhydrous
magnesium sulfate and concentrated under reduced pressure. The
residue was purified via chromatography on silica gel column using
hexane/ethyl acetate=9/1 as the eluant to afford the desired
compound (2.84 g) as a colorless oil.
[1694] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.23 (3H, t,
J=7.0 Hz), 2.30 (3H, s), 3.15-3.28 (2H, m), 4.15-4.25 (2H, m),
4.70-4.79 (1H, m), 5.08 (2H, s), 6.78 (2H, d, J=8.5 Hz), 6.95 (2H,
d, J=8.5 Hz), 7.07 (2H, d, J=8.5 Hz), 7.26 (2H, d, J=8.5 Hz),
7.32-7.60 (5H, m).
[1695] (c) Ethyl
3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionate
[1696] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-methylphe- noxy)propionate (2.84 g),
which is the product of Reference example 35(b), and palladium on
carbon (284 mg) and the reaction mixture was treated to afford the
desired compound (2.27 g) as a syrup.
[1697] NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t, J=7.0
Hz), 2.25 (3H, s), 3.09-3.18 (2H, m), 4.16 (2H, q, J=7.0 Hz),
4.64-4.72 (1H, m). 4.76 (1H, brs), 6.65-6.79 (4H, m), 7.02 (2H, d,
J=8.5 Hz), 7.16 (2H, d, J=8.5 Hz).
[1698] (d) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-methylph-
enoxy)propionate
[1699] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-(4-methylpheno- xy)propionate (300 mg), which
is the product of Reference example 35(c), t-butyl
2-methanesulfonyloxyethylcarbamate (598 mg) and potassium carbonate
(691 mg) and the reaction mixture was treated to afford the title
compound (261 mg) as a colorless oil.
[1700] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 2.25 (3H, s), 3.12-3.18 (2H, m), 3.45-3.55
(2H, m), 3.99 (2H, t, J=5.0 Hz), 4.17 (2H, q, J=7.0 Hz), 4.69 (1H,
dd, J=5.5, 7.5 Hz), 4.96 (1H, brs), 6.72 (2H, d, J=8.5 Hz), 6.82
(2H, d, J=8.5 Hz), 7.02 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5
Hz).
Reference Example 36
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-t-butylphenoxy)prop-
ionate
[1701] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-t-butylphenoxy)propionate
[1702] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl 3-(4-benzyloxyphenyl)lactate
(5.00 g), which is the product of Reference example 1(b),
4-t-butylphenol (2.50 g), triphenylphosphine (5.24 g) and a
solution of diethylazodicarboxylate in toluene (40%, 8.80 ml) and
the reaction mixture was treated to afford the desired compound
(3.00 g) as a colorless oil.
[1703] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 1.26 (9H, s), 3.12-3.21 (2H, m), 4.17 (2H, q, J=7.0 Hz),
4.70 (1H, dd, J=5.5, 7.5 Hz), 5.04 (2H, s), 6.76 (2H, d, J=8.5 Hz),
6.90 (2H, d, J=8.5 Hz), 7.20-7.26 (4H, m), 7.31-7.45 (5H, m).
[1704] (b) Ethyl
2-(4-t-butylphenoxy)-3-(4-hydroxyphenyl)propionate
[1705] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-t-butylph- enoxy)propionate (3.00 g),
which is the product of Reference example 36(a) and palladium on
carbon (5%, 300 mg) and the reaction mixture was treated to afford
the desired compound (2.37 g) as a colorless oil.
[1706] NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t, J=7.0
Hz), 1.26 (9H, s), 3.13-3.20 (2H, m), 4.18 (2H, q, J=7.0 Hz), 4.69
(1H, dd, J=5.5, 7.5 Hz), 4.81 (1H, brs), 6.75 (2H, d, J=8.5 Hz),
6.76 (2H, d, J=8.5 Hz), 7.17 (2H, d, J=8.5 Hz), 7.24 (2H, d, J=8.5
Hz).
[1707] (c) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-t-butylp-
henoxy)propionate
[1708] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl
2-(4-t-butylphenoxy)-3-(4-hydroxyphe- nyl)propionate (2.37 g),
which is the product of Reference example 36(b), t-butyl
2-methanesulfonyloxyethylcarbamate (3.60 g) and potassium carbonate
(4.78 g) and the reaction mixture was treated to afford the title
compound (3.13 g) as a colorless oil.
[1709] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 1.26 (9H, s), 1.45 (9H, s), 3.13-3.19 (2H, m), 3.51 (2H,
q, J=5.0 Hz), 3.99 (2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz),
4.66-4.72 (1H, m), 4.90-5.02 (1H, m), 6.76 (2H, d, J=8.5 Hz), 6.82
(2H, d, J=8.5 Hz), 7.22 (2H, d, J=8.5 Hz), 7.24 (2H, d, J=8.5
Hz).
Reference Example 37
Ethyl 3-[4-(2-aminoethoxy)phenyl]-2-(4-fluorophenoxy)propionate
[1710] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-fluorophenoxy)propionate
[1711] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl 3-(4-benzyloxyphenyl)lactate
(10.0 g), which is the product of Reference example 1(b),
4-fluorophenol (4.15 g), triphenylphosphine (10.6 g) and
diethylazodicarboxylate (6.40 ml) and the reaction mixture was
treated to afford the desired compound (7.00 g) as a colorless
oil.
[1712] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (3H, t,
J=7.0 Hz), 3.16 (2H, d, J=6.5 Hz), 4.16 (2H, q, J=7.0 Hz), 4.66
(1H, t, J=6.5 Hz), 5.04 (2H, s), 6.72-6.80 (2H, m), 6.89-6.97 (4H,
m), 7.21 (2H, d, J=8.5 Hz), 7.31-7.48 (5H, m).
[1713] (b) Ethyl
2-(4-fluorophenoxy)-3-(4-hydroxyphenyl)propionate
[1714] A solution of ethyl
3-(4-benzyloxyphenyl)-2-(4-fluorophenoxy)propio- nate (7.00 g),
which is the product of Reference example 37(a) in a solution of
hydrogen bromide in acetic acid (25%, 70 ml) was stirred at ambient
temperature for 3 hours. The reaction mixture was concentrated
under reduced pressure. Potassium carbonate (6.90 g) was added to a
solution of the residue in ethanol (70 ml). This mixture was
stirred at ambient temperature for 4 hours. The reaction mixture
was concentrated under reduced pressure. The residue was
partitioned between ethyl acetate and water and the layers were
separated. The ethyl acetate layer was dried over anhydrous
magnesium sulfate and concentrated under reduced pressure. The
residue was purified via chromatography on a silica gel column
using hexane/ethyl acetate=9/1-4/1 as the eluant to afford the
desired compound (2.75 g) as a white powder.
[1715] mp 80-81.degree. C.
[1716] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.15 (2H, d, J=6.5 Hz), 4.17 (2H, q, J=7.0 Hz), 4.65
(1H, t, J=6.5 Hz), 4.76 (1H, s), 6.71-6.80 (4H, m), 6.87-6.95 (2H,
m), 7.16 (2H, d, J=8.5 Hz).
[1717] (c) Ethyl
2-(4-fluorophenoxy)-3-[4-[2-(tetrahydropyran-2-yloxy)etho-
xy]phenyl]propionate
[1718] In a similar manner to that described in Reference example
3(e), a reaction was carried out using ethyl
2-(4-fluorophenoxy)-3-(4-hydroxyphen- yl)propionate (2.75 g), which
is the product of Reference example 37(b),
2-(2-bromoethyoxy)tetrahydropyran (2.08 g)and potassium carbonate
(3.75 g) and the reaction mixture was treated to afford the desired
compound (3.75 g) as a colorless oil.
[1719] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.48-1.90 (6H, m), 3.16 (2H, d, J=6.5 Hz), 3.49-3.57
(1H, m), 3.77-3.95 (2H, m), 4.00-4.21 (5H, m), 4.60-4.73 (2H, m),
6.74-6.79 (2H, m), 6.84-6.95 (4H, m), 7.20 (2H, d, J=8.5 Hz).
[1720] (d) Ethyl
2-(4-fluorophenoxy)-3-[4-(2-hydroxyethoxy)phenyl]propiona- te
[1721] In a similar manner to that described in Reference example
3(f), a reaction was carried out using ethyl
2-(4-fluorophenoxy)-3-[4-[2-(tetrahy-
dropyran-2-yloxy)ethoxy]phenyl]propionate (3.75 g), which is the
product of Reference example 37(c), and p-toluensulfonic acid
monohydrate (2.15 g) and the reaction mixture was treated to afford
the desired compound (2.68 g) as a colorless oil.
[1722] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.25 (3H, t,
J=7.0 Hz), 2.06 (1H, t, J=6.5 Hz), 3.20-3.23 (2H, m), 3.98-4.02
(2H, m), 4.10-4.13 (2H, m), 4.22 (2H, q, J=7.0 Hz), 4.71 (1H, dd,
J=6.0, 7.0 Hz), 6.80-7.00 (6H, m), 7.25-7.28 (2H, m).
[1723] (e) Ethyl
2-(4-fluorophenoxy)-3-[4-(2-methanesulfonyloxyethoxy)phen-
yl]propionate
[1724] In a similar manner to that described in Reference example
3(g), a reaction was carried out using ethyl
2-(4-fluorophenoxy)-3-[4-(2-hydroxye- thoxy)phenyl]propionate (2.68
g), which is the product of Reference example 37(d), triethylamine
(1.61 ml) and methanesulfonyl chloride (0.65 ml) and the reaction
mixture was treated to afford the desired compound (3.17 g) as a
pale yellow oil.
[1725] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.08 (3H, s), 3.17 (2H, d, J=6.5 Hz), 4.18 (2H, q, J=7.0
Hz), 4.20-4.24 (2H, m), 4.54-4.58 (2H, m), 4.66 (1H, t, J=6.5 Hz),
6.74-6.96 (6H, m), 7.23 (2H, d, J=8.5 Hz).
[1726] (f) Ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-fluorophenoxy)propionate
[1727] In a similar manner to that described in Reference example
3(h), a reaction was carried out using ethyl
2-(4-fluorophenoxy)-3-[4-(2-methanes-
ulfonyloxyethoxy)phenyl]propionate (3.16 g), which is the product
of Reference example 37(e), and sodium azide (1.45 g) and the
reaction mixture was treated to afford the desired compound (2.67
g) as a colorless oil.
[1728] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 3.58 (2H, t, J=5.0 Hz),
4.08-4.23 (4H, m), 4.66 (1H, t, J=6.5 Hz), 6.74-6.96 (6H, m),
7.20-7.25 (2H, m).
[1729] (g) Ethyl
3-[4-(2-aminoethoxy)phenyl]-2-(4-fluorophenoxy)propionate
[1730] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-[4-(2-azidoethoxy)phenyl]-2-(4-flu- orophenoxy)propionate (2.60
g), which is the product of Reference example 37(f), and palladium
on carbon (5%, 250 mg) and the reaction mixture was treated to
afford the title compound (2.30 g) as a colorless oil.
[1731] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 2.99-3.15 (2H, m), 3.16 (2H, d, J=6.5 Hz), 3.97 (2H, t,
J=5.0 Hz), 4.17 (2H, q, J=7.0 Hz), 4.66 (1H, t, J=6.5 Hz),
6.72-6.96 (6H, m), 7.1-7.27 (2H, m).
Reference Example 38
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-chlorophenoxy)propi-
onate
[1732] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-chlorophenoxy)propionate
[1733] In a similar manner to that described in Reference example
35(b), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-methanesulfo- nyloxypropionate (8.82 g),
which is the product of Reference example 35(a), 4-chlorophenol
(3.00 g) and potassium carbonate (6.44 g) and the reaction mixture
was treated to afford the desired compound (5.99 g) as colorless
crystals.
[1734] mp 63-64.degree. C.
[1735] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.18 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 4.16 (2H, q, J=7.0 Hz), 4.69
(1H, t, J=6.5 Hz), 5.04 (2H, s), 6.75 (2H, d, J=9.0 Hz), 6.91 (2H,
d, J=8.5 Hz), 7.13-7.23 (4H, m), 7.25-7.55 (5H, m).
[1736] (b) Ethyl
2-(4-chlorophenoxy)-3-(4-hydroxyphenyl)propionate
[1737] In a similar manner to that described in Reference example
37(b), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-chlorophe- noxy)propionate (5.99 g),
which is the product of Reference example 38(a), a solution of
hydrogen bromide in acetic acid (25%, 60 ml) and potassium
carbonate (4.68 g) and the reaction mixture was treated to afford
the desired compound (3.85 g) as colorless crystals.
[1738] mp 90-93.degree. C.
[1739] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.16 (2H, d, J=6.5 Hz), 4.17 (2H, q, J=7.0 Hz), 4.69
(1H, t, J=6.5 Hz), 4.95 (1H, brs), 6.76 (4H, d, J=8.5 Hz), 7.15
(2H, d, J=8.5 Hz), 7.18 (2H, d, J=8.5 Hz).
[1740] (c) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-chloroph-
enoxy)propionate
[1741] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
2-(4-chlorophenoxy)-3-(4-hydroxyphenyl)propio- nate (1.01 g), which
is the product of Reference example 38(b), t-butyl
2-hydroxyethylcarbamate (1.27 g), triphenylphosphine (2.06 g) and
diethylazodicarboxylate (1.37 g) and the reaction mixture was
treated to afford the title compound (1.14 g) as a colorless
oil.
[1742] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 3.17 (2H, t, J=6.5 Hz), 3.43-3.57 (2H, m),
3.99 (2H, t, J=5.0 Hz), 4.17 (2H, q, J=7.0 Hz), 4.69 (1H, t, J=6.5
Hz), 4.96 (1H, brs), 6.76 (2H, d, J=8.5 Hz), 6.82 (2H, d, J=8.5
Hz), 7.10-7.20 (4H, m).
Reference Example 39
Ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phenyl]propion-
ate
[1743] (a) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-hydroxyprop-
ionate
[1744] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl 4-hydroxyphenylactate
(224 mg), t-butyl 2-methanesulfonyloxyethylcarbamate (638 mg) and
potassium carbonate (737 mg) and the reaction mixture was treated
to afford the title compound (205 mg) as a colorless oil.
[1745] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.29 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 2.72 (1H, d, J=6.0 Hz), 2.91 (1H, dd,
J=6.5, 14.0 Hz), 3.07 (1H, dd, J=4.5, 14.0 Hz), 3.52 (2H, q, J=5.0
Hz), 3.99 (2H, t, J=5.0 Hz), 4.22 (2H, q, J=7.0 Hz), 4.39 (1H, ddd,
J=4.5, 6.0, 6.5 Hz), 4.98 (1H, brt), 6.82 (2H, d, J=8.5 Hz), 7.13
(2H, d, J=8.5 Hz).
[1746] (b) Ethyl
2-hydroxy-3-[4-[2-(4-pyridine-2-ylbenzoylamino)ethoxy]phe-
nyl]propionate
[1747] In a similar manner to that described in Example 126, a
reaction was carried out using ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2- -hydroxypropionate
(168 mg), 4-pyridine-2-ylbenzoylchloride hydrochloride (126 mg) and
triethylamine (0.28 ml) and the reaction mixture was treated to
afford the title compound (188 mg) as colorless crystals.
[1748] mp 97-99.degree. C.
[1749] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.29 (3H, t,
J=7.0 Hz), 2.92 (1H, d, J=6.5, 14.0 Hz), 3.07 (1H, dd, J=4.5, 14.0
Hz), 3.90 (2H, q, J=5.0 Hz), 4.16 (2H, t, J=5.0 Hz), 4.22 (2H, q,
J=7.0 Hz), 4.39 (1H, dd, J=4.5, 6.5 Hz), 6.66 (1H, brt), 6.87 (2H,
d, J=8.5 Hz), 7.15 (2H, d, J=8.5 Hz), 7.27-7.32 (1H, m), 7.73-7.84
(2H, m), 7.89 (2H, d, J=8.5 Hz), 8.07 (2H, d, J=8.5 Hz), 8.73 (1H,
d, J=5.0 Hz).
Reference Example 40
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-trifluoromethoxyphe-
noxy)propionate
[1750] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-trifluoromethoxyphenoxy)propio- nate
[1751] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl 3-(4-benzyloxyphenyl)lactate
(4.50 g), which is the product of Reference example 1(b),
4-trifluoromethoxyphenol (2.33 ml), triphenylphosphine (4.71 g) and
solution of diethylazodicarboxylate in toluene (40%, 8.15 ml) and
the reaction mixture was treated to afford the desired compound
(4.19 g) as colorless crystals.
[1752] mp 34-36.degree. C.
[1753] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.18 (2H, d, J=6.5 Hz), 4.18 (2H, q, J=7.0 Hz), 4.70
(1H, t, J=6.5 Hz), 5.04 (2H, s), 6.82 (2H, d, J=8.5 Hz), 6.91 (2H,
d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz),
7.29-7.46 (5H, m).
[1754] (b) Ethyl
3-(4-hydroxyphenyl)-2-(4-trifluoromethoxyphenoxy)propiona- te
[1755] In a similar manner to that described in Reference example
37(b), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-trifluoro- methoxyphenoxy)propionate
(4.08 g), which is the product of Reference example 40(a), a
solution of hydrogen bromide in acetic acid (25%, 40 ml) and
potassium carbonate (1.68 g) and the reaction mixture was treated
to afford the desired compound (2.98 g) as a colorless oil.
[1756] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.17 (2H, d, J=6.5 Hz), 3.50 (1H, brs), 4.18 (2H, q,
J=7.0 Hz), 4.70 (1H, t, J=6.5 Hz), 6.76 (2H, d, J=8.5 Hz), 6.82
(2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.15 (2H, d, J=8.5
Hz).
[1757] (c) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-trifluor-
omethoxyphenoxy)propionate
[1758] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-(4-trifluorome- thoxyphenoxy)propionate (2.93
g), t-butyl 2-methanesulfonyloxyethylcarbama- te (4.73 g) and
potassium carbonate (5.46 g) and the reaction mixture was treated
to afford the title compound (2.28 g) as a colorless oil.
[1759] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.44 (9H, s), 3.18 (2H, d, J=6.5 Hz), 3.51 (2H, q, J=5.0
Hz), 3.99 (2H, t, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.70 (1H, t,
J=6.5 Hz), 4.97 (1H, brt), 6.81 (2H, d, J=8.5 Hz), 6.83 (2H, d,
J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz).
Reference Example 41
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-cyanophenoxy)propio-
nate
[1760] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(4-cyanophenoxy)propionate
[1761] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl 3-(4-benzyloxyphenyl)lactate
(1.01 g), which is the product of Reference example 1(b),
4-cyanophenol (481 mg), triphenylphosphine (1.06 g) and solution of
diethylazodicarboxylate in toluene (40%, 0.73 ml) and the reaction
mixture was treated to afford the desired compound (619 mg) as a
colorless oil.
[1762] .sup.1-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.21 (2H, d, J=6.5 Hz), 4.17 (2H, q, J=7.0 Hz), 4.79
(1H, t, J=6.5 Hz), 5.04 (2H, s), 6.88 (2H, d, J=8.5 Hz), 6.91 (2H,
d, J=8.5 Hz), 7.19 (2H, d, J=8.5 Hz), 7.28-7.48 (5H, m), 7.54 (2H,
d, J=8.5 Hz).
[1763] (b) Ethyl
2-(4-cyanophenoxy)-3-(4-hydroxyphenyl)propionate
[1764] In a similar manner to that described in Reference example
1(d), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(4-cyanophen- oxy)propionate (376 mg),
which is the product of Reference example 41(a), and palladium on
carbon (5%, 65 mg) and the reaction mixture was treated to afford
the title compound (293 mg) as a colorless oil.
[1765] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7.0 Hz), 3.19 (2H, d, J=6.5 Hz), 4.18 (2H, q, J=7.0 Hz), 4.78
(1H, t, J=6.5 Hz), 6.76 (2H, d, J=8.5 Hz), 6.88 (2H, d, J=9.0 Hz),
7.14 (2H, d, J=8.5 Hz), 7.62 (2H, d, J=9.0 Hz).
[1766] (c) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-cyanophe-
noxy)propionate
[1767] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl
2-(4-cyanophenoxy)-3-(4-hydroxypheny- l)propionate (293 mg),
t-butyl 2-methanesulfonyloxyethylcarbamate (560 mg) and potassium
carbonate (520 mg) and the reaction mixture was treated to afford
the title compound (245 mg) as a colorless oil.
[1768] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 3.21 (2H, d, J=6.5 Hz), 3.52 (2H, q, J=5.0
Hz), 3.99 (2H, t, J=5.0 Hz), 4.19 (2H, q, J=7.0 Hz), 4.79 (1H, t,
J=6.5 Hz), 4.97 (1H, brt), 6.83 (2H, d, J=8.5 Hz), 6.88 (2H, d,
J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz).
Reference Example 42
Methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-methylthiophenoxy)-
propionate
[1769] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(389 mg), which is obtained in a similar manner to that described
in Reference example 39(a), 4-methylthiophenol (241 mg),
triphenylphosphine (463 mg) and solution of diethylazodicarboxylate
in toluene (40%, 0.31 ml) and the reaction mixture was treated to
afford the desired compound (265 mg) as a colorless oil which
contained some impurities.
[1770] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.45 (9H, s),
2.43 (3H, s), 3.17 (2H, d, J=6.5 Hz), 3.52 (2H, q, J=5.0 Hz), 3.72
(3H, s), 3.99 (2H, t, J=5.0 Hz), 4.72 (1H, t, J=6.5 Hz), 4.98 (1H,
brt), 6.78 (2H, d, J=8.5 Hz), 6.82 (2H, d, J=8.5 Hz), 7.20 (4H, d,
J=8.5 Hz).
Reference Example 43
Methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-methanesulfonylphe-
noxy)propionate
[1771] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(518 mg), which is obtained in a similar manner to that described
in Reference example 39(a), 4-methanesulfonylphenol (394 mg),
tributylphosphine (0.57 ml) instead of triphenylphosphine and
1,1'-(azodicarbonyl)dipiperidine (578 mg) instead of
diethylazodicarboxylate and the reaction mixture was treated to
afford the desired compound (441 mg) as a mass of foam.
[1772] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.44 (9H, s),
3.00 (3H, s), 3.22 (2H, d, J=6.5 Hz), 3.51 (2H, q, J=5.0 Hz), 3.74
(3H, s), 3.99 (2H, t, J=5.0 Hz), 4.84 (1H, t, J=6.5 Hz), 4.97 (1H,
brt), 6.83 (2H, d, J=8.5 Hz), 6.94 (2H, d, J=9.0 Hz), 7.19 (2H, d,
J=8.5 Hz), 7.82 (2H, d, J=9.0 Hz).
Reference Example 44
Methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-fluorophenoxy)prop-
ionate
[1773] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(420 mg), which is obtained in a similar manner to that described
in Reference example 39(a), 4-fluorophenol (284 mg),
triphenylphosphine (666 mg) and solution of diethylazodicarboxylate
in toluene (40%, 1.10 ml) and the reaction mixture was treated to
afford the desired compound (314 mg) as a colorless oil.
[1774] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.45 (9H, s),
3.16 (2H, d, J=6.5 Hz), 3.52 (2H, q, J=5.0 Hz), 3.72 (3H, s), 3.99
(2H, t, J=5.0 Hz), 4.67 (1H, t, J=6.5 Hz), 4.96 (1H, brt), 6.76
(2H, dd, J=4.0, 9.0 Hz), 6.83 (2H, d, J=8.5 Hz), 6.92 (2H, dd,
J=8.0, 9.0 Hz), 7.20 (2H, d, J=8.5 Hz).
Reference Example 45
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-isopropylphenoxy)-2-
-methylpropionate
[1775] In a similar manner to that described in Reference example
25, a reaction was carried out using ethyl
3-(4-hydroxyphenyl)-2-(4-isopropylph- enoxy)-2-methylpropionate
(4.85 g), which is the product of Reference example 9(b), t-butyl
2-methanesulfonyloxy-ethylcarbamate (8.47 g) and potassium
carbonate (9.78 g) and the reaction mixture was treated to afford
the title compound (6.23 g) as a colorless oil.
[1776] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.15-1.28
(9H, m), 1.37 (3H, s), 1.45 (9H, s), 2.83 (1H, septet, J=7.0 Hz),
3.10 (1H, d, J=13.5 Hz), 3.25 (1H, d, J=13.5 Hz), 3.46-3.58 (2H,
m), 4.00 (2H, t, J=5.0 Hz), 4.21 (2H, q, J=7.0 Hz), 4.95-5.05 (1H,
m), 6.75 (2H, d, J=8.5 Hz), 6.81 (2H, d, J=8.5 Hz), 7.06 (2H, d,
J=8.5 Hz), 7.17 (2H, d, J=8.5 Hz).
Reference Example 46
Methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-phenylthiopropionate
[1777] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(366 mg), which is obtained in a similar manner to that described
in Reference example 39(a), thiophenol (0.17 ml),
triphenylphosphine (438 mg) and solution of diethylazodicarboxylate
in toluene (40%, 0.29 ml) and the reaction mixture was treated to
afford the desired compound (209 mg) as a colorless oil.
[1778] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.45 (9H, s),
3.00 (1H, dd, J=6.5, 13.5 Hz), 3.13 (1H, dd, J=9.5, 13.5 Hz), 3.52
(2H, t, J=5.0 Hz), 3.58 (3H, s), 3.86 (1H, dd, J=6.5, 9.5 Hz), 3.98
(2H, t, J=5.0 Hz), 5.00 (1H, brt), 6.80 (2H, d, J=8.5 Hz), 7.10
(2H, d, J=8.5 Hz), 7.30-7.40 (3H, m), 7.41-7.56 (2H, m).
Reference Example 47
Methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(pyridine-3-yloxy)pro-
pionate
[1779] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(404 mg), which is obtained in a similar manner to that described
in Reference example 39(a), 3-hydroxypyridine (227 mg),
triphenylphosphine (938 mg) and solution of diethylazodicarboxylate
in toluene (40%, 0.65 ml) and the reaction mixture was treated to
afford the desired compound (345 mg) as a colorless oil.
.sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.44 (9H, s), 3.21
(2H, d, J=6.5 Hz), 3.52 (2H, q, J=5.0 Hz), 3.74 (3H, s), 3.99 (2H,
t, J=5.0 Hz), 4.78 (1H, t, J=6.5 Hz), 4.96 (1H, brt), 6.84 (2H, d,
J=8.5 Hz), 7.11 (1H, d, J=8.5 Hz), 7.18 (1H, dd, J=5.0, 8.5 Hz),
7.20 (2H, d, J=8.5 Hz), 8.23 (1H, d, J=5.0 Hz), 8.24 (1H, s).
Reference Example 48
Methyl
2-(benzoxazole-2-ylthio)-3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl-
]propionate
[1780] In a similar manner to that described in Example 122, a
reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-- 2-hydroxypropionate
(415 mg), which is obtained in a similar manner to that described
in Reference example 39(a), 2-mercaptobenzoxazole (277 mg),
tributylphosphine (0.46 ml) instead of triphenylphosphine and
1,1'-(azodicarbonyl)dipiperidine (460 mg) instead of
diethylazodicarboxylate and the reaction mixture was treated to
afford the desired compound (665 mg) as a colorless oil which
contained some impurities.
[1781] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.46 (9H, s),
3.26 (1H, dd, J=7.0, 14.0 Hz), 3.35 (1H, dd, J=7.5, 14.0 Hz), 3.51
(2H, q, J=5.0 Hz), 3.71 (3H, s), 3.96 (2H, t, J=5.0 Hz), 4.76 (1H,
dd, J=7.0, 7.5 Hz), 4.89 (1H, brt), 6.81 (2H, d, J=8.0 Hz), 7.17
(2H, d, J=8.0 Hz), 7.22-7.29 (2H, m), 7.43 (1H, d, J=7.5 Hz), 7.60
(1H, d, J=6.0 Hz).
Reference Example 49
Methyl
2-benzyloxy-3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]propionate
[1782] In a similar manner to that described in Reference example
1(c), a reaction was carried out using methyl
3-[4-(2-t-butoxycarbonylaminoethoxy- )phenyl]-2-hydroxypropionate
(398 mg), which is obtained in a similar manner to that described
in Reference example 39(a), benzylbromide (0.28 ml), hydride (55%
suspension in oil, 168 mg) and tetrabutylammonium iodide (43 mg)
and the reaction mixture was treated to afford the desired compound
(133 mg) as a colorless oil.
[1783] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.46 (9H, s),
2.99 (1H, d, J=7.5 Hz), 3.00 (1H, d, J=5.5 Hz), 3.53 (2H, q, J=5.0
Hz), 3.71 (3H, s), 4.00 (2H, t, J=5.0 Hz), 4.09 (1H, dd, J=5.5, 7.5
Hz), 4.37 (1H, d, J=12.0 Hz), 4.65 (1H, d, J=12.0 Hz), 5.00 (1H,
brt), 6.81 (2H, d, J=8.5 Hz), 7.13 (2H, d, J=8.5 Hz), 7.17-7.22
(2H, m), 7.25-7.31 (3H, m).
Reference Example 50
Dibenzyl
2-(3-phenylpropyl)-2-[4-[3-(4-pyridine-2-ylbenzoylamino)propyl]be-
nzyl]malonate
[1784] (a) 4-(3-Benzyloxycarbonylaminopropyl)benzylalcohol
[1785] A solution of methyl 4-(2-cyanoethyl)benzoate (10.0 g) in
tetrahydrofuran (80 ml) was added dropwise to a suspension of
lithium aluminum hydride (4.00 g) in tetrahydrofuran (180 ml) in an
ice bath. The mixture was stirred at ambient temperature for 1 hour
and at 60.degree. C. for 3 hours. To the reaction mixture, water (4
ml), aqueous sodium hydroxide solution (15%, 4 ml) and water (12
ml) were added successively and the mixture was stirred for 1 hour.
The insoluble material in the reaction mixture was removed by
filtration and washed with tetrahydrofuran.
N-Benzyloxycarbonyl-5-norbornene-2,3-dicarboxyimide (16.5 g) was
added to the mixture of the filtrate and the tetrahydrofuran
solution and this mixture was stirred at ambient temperature for 3
hours. The reaction mixture was concentrated. The residue was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
chloride solution and saturated aqueous sodium hydrogencarbonate
solution and dried over anhydrous magnesium sulfate and
concentrated. The residue was purified via chromatography on a
silica gel column using hexane/ethyl acetate=1/1 as the eluant to
afford the desired compound (5.67 g) as crystals.
[1786] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.82 (2H,
quintuplet, J=7.5 Hz), 2.64 (2H, t, J=7.5 Hz), 3.22 (2H, dt, J=6.5,
7.5 Hz), 4.65 (2H, s), 4.75 (1H, brs), 5.09 (2H, s), 7.16 (2H, d,
J=8.0 Hz), 7.26-7.36 (7H, m).
[1787] (b)
4-[3-(4-Pyridine-2-ylbenzoylamino)propyl]benzylalcohol
[1788] Palladium on carbon (5%, 0.15 g) was added to a solution of
4-(3-benzyloxycarbonylaminopropyl)benzylalcohol (1.00 g), which is
the product of Reference example 50(a) in ethanol (20 ml). The
mixture was stirred under an atmosphere of hydrogen at ambient
temperature for 2 hours. The catalyst was removed by filtration and
the filtrate was concentrated to afford
4-(3-aminopropyl)benzylalcohol as a gum. In a similar manner to
that described in Example 5, a reaction was carried out using
4-(3-aminopropyl)benzylalcohol, 4-pyridine-2-ylbenzoic acid (668
mg) and carbonyldiimidazole (650 mg) and the reaction mixture was
treated to afford the desired compound (0.74 g) as colorless
crystals.
[1789] mp 118-120.degree. C.
[1790] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 2.00 (2H,
quintuplet, J=7.5 Hz), 2.75 (2H, t, J=7.5 Hz), 3.53 (2H, dt, J=6.5,
7.5 Hz), 4.65 (2H, s), 6.10 (1H brs), 7.20-7.31 (5H, m), 7.72-7.80
(4H, m), 8.02 (2H, d, J=8.5 Hz), 8.71 (1H, d, J=5.0 Hz).
[1791] (c)
4-[3-(4-pyridine-2-ylbenzoylamino)propyl]benzylchloride
[1792] Methanesulfonyl chloride (294 mg) and triethylamine (0.37
ml) were successively added to a solution of
4-[3-(4-pyridine-2-ylbenzoylamino)pro- pyl]benzylalcohol (0.74 g)
in dichloromethane (20 ml). The mixture was allowed to stand at
ambient temperature for 16 hours. The reaction mixture was
concentrated. The residue was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and washed with
saturated aqueous sodium chloride solution and dried over anhydrous
magnesium sulfate and concentrated to afford crystals. The crystals
were washed with a small amount of diisopropyl ether to afford the
desired compound (0.68 g).
[1793] mp 115-117.degree. C.
[1794] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.99 (2H,
quintuplet, J=7.5 Hz), 2.75 (2H, t, J=7.5 Hz), 3.53 (2H, dt, J=6.5,
7.5 Hz), 6.15 (1H, brs), 7.21-7.34 (5H, m), 7.76-7.82 (4H, m), 8.06
(2H, d, J=8.5 Hz) 8.70-8.73 (1H m).
[1795] (d) Dibenzyl
2-(3-phenylpropyl)-2-[4-[3-(4-pyridine-2-ylbenzoylamin-
o)propyl]benzyl]malonate
[1796] In a similar manner to that described in Reference example
2(a), a reaction was carried out using
4-[3-(4-pyridine-2-ylbenzoylamino)propyl]b- enzylchloride (488 mg),
which is the product of Reference example 50(c), sodium hydride
(55% suspension in oil, 64 mg) and benzyl (3-phenylpropyl)malonate
(540 mg) and the reaction mixture was treated to afford the title
compound (0.65 g) as a syrup. .sup.1H-NMR (270 MHz, CDCl.sub.3):
.delta. ppm 1.44-1.58 (2H, m), 1.78-1.87 (2H, m), 1.92 (2H, t,
J=7.5 Hz), 2.52 (2H, t, J=7.5 Hz), 2.65 (2H, t, J=7.5 Hz), 3.19
(2H, s), 3.49 (2H, dt, J=6.0, 7.5 Hz), 5.05 (1H, d, J=12.0 Hz),
5.09 (1H, d, J=12.0 Hz), 6.16 (1H, brt, J=6.0 Hz), 6.78 (2H, d,
J=8.0 Hz), 6.96 (2H, d, J=8.0 Hz), 7.05 (2H, d, J=8.0 Hz),
7.17-7.35 (14H, m), 7.76-7.82 (4H, m), 8.06 (2H, d, J=8.5 Hz), 8.71
(1H, d, J=5.0 Hz).
Reference Example 51
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)-3-chlorophenyl]-2-phenoxypropio-
nate
[1797] (a) Ethyl
3-(3-chloro-4-hydroxyphenyl)-2-phenoxypropionate
[1798] A solution of sulfuryl chloride (0.71 ml) in diethyl ether
(5 ml) was added dropwise to a solution of ethyl
3-(4-hydroxyphenyl)-2-phenoxypr- opionate (1.43 g) in diethyl ether
(20 ml) at ambient temperature. The mixture was stirred for 8 hour
and allowed to stand overnight. The reaction mixture was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
hydrogencarbonate solution and saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=10/3 as the eluant to afford the desired compound (1.09 g)
as a colorless oil.
[1799] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.15 (1H, d, J=5.0 Hz), 3.16 (1H, d, J=7.5 Hz), 4.19
(2H, q, J=7.0 Hz), 4.73 (1H, dd, J=5.0, 7.5 Hz), 5.49 (1H, s), 6.84
(2H, d, J=8.0 Hz), 6.94 (1H, d, J=8.5 Hz), 6.96 (1H, t, J=8.0 Hz),
7.12 (1H, dd, J=2.0, 8.5 Hz), 7.25 (2H, t, J=8.0 Hz), 7.28 (1H, d,
J=2.0 Hz).
[1800] (b) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)-3-chlorophenyl]-2-ph-
enoxypropionate
[1801] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
3-(3-chloro-4-hydroxyphenyl)-2-phenoxypropion- ate (761 mg), which
is the product of Reference example 51(a), t-butyl
2-hydroxyethylcarbamate (0.96 g), triphenylphosphine (1.55 g) and
solution of diethylazodicarboxylate in toluene (40%, 2.69 ml) and
the reaction mixture was treated to afford the desired compound
(1.03 g) as a colorless oil.
[1802] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 3.15 (1H, d, J=5.5 Hz), 3.16 (1H, d, J=7.5
Hz), 3.56 (2H, q, J=5.0 Hz), 4.05 (2H, t, J=5.0 Hz), 4.19 (2H, q,
J=7.0 Hz), 4.73 (1H, dd, J=5.5, 7.5 Hz), 5.06 (1H, brt), 6.84 (2H,
d, J=8.0 Hz), 6.85 (1H, d, J=8.5 Hz), 6.96 (1H, t, J=8.0 Hz), 7.15
(1H, dd, J=2.0, 8.5 Hz), 7.25 (2H, t, J=8.0 Hz), 7.33 (1H, d, J=2.0
Hz).
Reference Example 52
Ethyl
3-[3-bromo-4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-phenoxypropion-
ate
[1803] (a) Ethyl
3-(3-bromo-4-hydroxyphenyl)-2-phenoxypropionate
[1804] N-bromosuccinimide (1.12 g) was added to a solution of ethyl
3-(4-hydroxyphenyl)-2-phenoxypropionate (1.43 g), which is the
product of reference example 4(c) in chloroform (20 ml) at ambient
temperature. The mixture was stirred at 70.degree. C. for 4 hour
and concentrated under reduced pressure. The residue was
partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
chloride solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on silica gel column using hexane/ethyl acetate=4/1
as the eluant to afford the desired compound (1.41 g) as a
colorless oil.
[1805] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7.0 Hz), 3.148 (1H, d, J=5.5 Hz), 3.153 (1H, d, J=7.0 Hz), 4.18
(2H, q, J=7.0 Hz), 4.72 (1H, dd, J=5.5, 7.0 Hz), 5.45 (1H, brs),
6.84 (2H, d, J=8.0 Hz), 6.94 (1H, d, J=8.5 Hz), 6.96 (1H, t, J=8.0
Hz), 7.16 (1H, dd, J=2.0, 8.5 Hz), 7.25 (2H, t, J=8.0 Hz), 7.42
(1H, d, J=2.0 Hz).
[1806] (b) Ethyl
3-[3-bromo-4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-phe-
noxypropionate
[1807] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
3-(3-bromo-4-hydroxyphenyl)-2-phenoxypropiona- te (374 mg), which
is the product of Reference example 52(a), t-butyl
2-hydroxyethylcarbamate (403 mg), triphenylphosphine (672 mg) and a
solution of diethylazodicarboxylate in toluene (40%, 1.16 ml) and
the reaction mixture was treated to afford the desired compound
(466 mg) as a colorless oil.
[1808] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.21 (3H, t,
J=7.0 Hz), 1.45 (9H, s), 3.15 (1H, d, J=5.5 Hz), 3.16 (1H, d, J=7.0
Hz), 3.56 (2H, q, J=5.0 Hz), 4.04 (2H, t, J=5.0 Hz), 4.19 (2H, q,
J=7.0 Hz), 4.72 (1H, dd, J=5.5, 7.0 Hz), 5.08 (1H, brt), 6.82 (1H,
d, J=8.5 Hz), 6.85 (2H, d, J=8.0 Hz), 6.96 (1H, t, J=7.5 Hz), 7.20
(1H, dd, J=2.0, 8.5 Hz), 7.25 (2H, dd, J=7.5, 8.0 Hz), 7.50 (1H, d,
J=2.0 Hz).
Reference Example 53
Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)-3-nitrophenyl]-2-phenoxypropion-
ate
[1809] (a) Ethyl
3-(4-hydroxy-3-nitrophenyl)-2-phenoxypropionate
[1810] Water (2.5 ml), concentrated aqueous hydrogen chloride
solution (1.17 ml) and sodium nitrate (297 mg) were added to a
solution of ethyl 3-(4-hydroxyphenyl)-2-phenoxypropionate (1.00 g),
which is the product of Reference example 4(c), in a mixture of
dichloromethane (4.0 ml) and diethyl ether (8.0 ml) at ambient
temperature. The mixture was stirred for 2.5 hours at the same
temperature and allowed to stand for 14 hours. The reaction mixture
was partitioned between ethyl acetate and water. The ethyl acetate
layer was separated and washed with saturated aqueous sodium
hydrogencarbonate solution and saturated aqueous sodium chloride
solution and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using hexane/ethyl
acetate=4/1 as the eluant to afford the desired compound (935 mg)
as a colorless oil.
[1811] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.23 (3H, t,
J=7.0 Hz), 3.23 (2H, d, J=6.0 Hz), 4.21 (2H, q, J=7.0 Hz), 4.76
(1H, t, J=6.0 Hz), 6.83 (2H, d, J=8.0 Hz), 6.97 (1H, t, J=7.5 Hz),
7.11 (1H, d, J=8.5 Hz), 7.25 (2H, dd, J=7.5, 8.0 Hz), 7.56 (1H, dd,
J=2.0, 8.5 Hz), 8.08 (1H, d, J=2.0 Hz).
[1812] (b) Ethyl
3-[4-(2-t-butoxycarbonylaminoethoxy)-3-nitrophenyl]-2-phe-
noxypropionate
[1813] In a similar manner to that described in Example 122, a
reaction was carried out using ethyl
3-(4-hydroxy-3-nitrophenyl)-2-phenoxypropiona- te (270 mg), which
is the product of Reference example 53(a), t-butyl
2-hydroxyethylcarbamate (322 mg), triphenylphosphine (535 mg) and a
solution of diethylazodicarboxylate in toluene (40%, 0.93 ml) and
the reaction mixture was treated to afford the desired compound
(349 mg) as a colorless oil.
[1814] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.23 (3H, t,
J=7.0 Hz), 1.44 (9H, s), 3.23 (2H, d, J=6.0 Hz), 3.57 (2H, q, J=5.0
Hz), 4.14 (2H, t, J=5.0 Hz), 4.21 (2H, q, J=7.0 Hz), 4.76 (1H, t,
J=6.0 Hz), 5.14 (1H, brt), 6.83 (2H, d, J=8.0 Hz), 6.97 (1H, t,
J=7.5 Hz), 7.00 (1H, d, J=8.5 Hz), 7.25 (2H, dd, J=7.5, 8.0 Hz),
7.50 (1H, dd, J=2.0, 8.5 Hz), 7.85 (1H, d, J=2.0 Hz).
Reference Example 54
Methyl
(S)-2-benzyloxycarbonylamino-3-[4-(2-t-butoxycarbonylaminoethoxy)ph-
enyl]propionate
[1815] In a similar manner to that described in Reference example
25, a reaction was carried out using N-benzyloxycarbonyl-L-tyrosine
methyl ester (4.94 g), t-butyl 2-methanesulfonyloxyethylcarbamate
(8.97 g) and potassium carbonate (10.4 g) and the reaction mixture
was treated to afford the title compound (3.32 g) as colorless
crystals.
[1816] mp 89-91.degree. C.
[1817] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.62 (9H, s),
3.00-3.10 (2H, m), 3.48-3.56 (2H, m), 3.72 (3H, s), 3.98 (2H, t,
J=5.0 Hz), 4.56-4.68 (1H, m), 4.99 (1H, brs), 5.10 (2H, ABq, J=12.5
Hz, .delta.=0.03 ppm), 5.15-5.24 (1H, m), 6.79 (2H, d, J=8.5 Hz),
7.00 (2H, d, J=8.5 Hz), 7.23-7.41 (5H, m).
Reference Example 55
Ethyl 3-(4-hydroxyphenyl)-2-(phenylamino)propionate
[1818] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(phenylamino)propionate
[1819] A mixture of ethyl
3-(4-benzyloxyphenyl)-2-methanesulfonyloxypropio- nate (4.00 g) and
aniline (5 ml) was stirred at 110.degree. C. for 24 hours. The
reaction mixture was purified via chromatography on silica gel
column using ethyl acetate/hexane=1/4 as the eluant to afford the
desired compound (3.94 g) as a syrup.
[1820] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.17 (3H, t,
J=7 Hz), 3.00-3.14 (2H, m), 4.12 (2H, dq, J=1.5, 7 Hz), 4.30 (1H,
t, J=6 Hz), 5.04 (2H, s), 6.60 (2H, d, J=8.5 Hz), 6.73 (1H, t,
J=7.5 Hz), 6.89 (2H, d, J=8.5 Hz), 7.09 (2H, d, J=8.5 Hz), 7.16
(2H, d, J=8.5 Hz), 7.31-7.44 (5H, m).
[1821] (b) Ethyl 3-(4-hydroxyphenyl)-2-(phenylamino)propionate
[1822] Palladium on carbon (5%, 0.80 g) was added to a solution of
ethyl 3-(4-benzyloxyphenyl)-2-(phenylamino)propionate (3.94 g),
which is the product of Reference example 55(a), in a mixture of
ethanol (40 ml) and tetrahydrofuran (20 ml). The mixture was
stirred under an atmosphere of hydrogen at 50.degree. C. for 6
hours. The catalyst was removed by filtration and the filtrate was
concentrated. The residue was purified via chromatography on a
silica gel column using ethyl acetate/hexane=1/2 as the eluant to
afford the title compound (2.95 g) as a syrup.
[1823] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7 Hz), 3.00-3.13 (2H, m), 4.13 (2H, dq, J=1, 7 Hz), 4.30 (1H,
brt, J=6 Hz), 4.88 (1H, brs), 6.60 (2H, d, J=8 Hz), 6.71-6.76 (3H,
m), 7.03 (2H, d, J=8 Hz), 7.14-7.20 (2H, m).
Reference Example 56
Ethyl 3-(4-hydroxyphenyl)-2-(N-ethyl-N-phenylamino)propionate
[1824] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(N-ethyl-N-phenylamino)propionate
[1825] In a similar manner to that described in Reference example
55(a), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-methanesulfo- nyloxypropionate (4.50 g) and
N-ethylaniline (5.6 ml) and the reaction mixture was treated to
afford a mixture of the desired compound and N-ethylaniline (6.30
g) as a syrup.
[1826] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm
1.07(3H,t,3H,J=7Hz), 1.14(3H, t, J=7 Hz), 3.01-3.45 (4H, m), 4.09
(2H, q, J=7 Hz), 4.39 (1H, t, J=7.5 Hz), 5.02 (2H, s), 6.66-6.75
(3H, m), 6.87 (2H, d, J=8 Hz), 7.10 (2H, d, J=8.5 Hz), 7.15-7.25
(2H, m), 7.31-7.44 (5H, m).
[1827] (b) Ethyl
2-(N-ethyl-N-phenylamino)-3-(4-hydroxyphenyl)propionate
[1828] In a similar manner to that described in Reference example
55(b), a reaction was carried out using the mixture (6.30 g), which
is the product of Reference example 56(a) and the reaction mixture
was treated to afford the title compound (2.37 g) as a syrup.
[1829] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.07 (3H, t,
J=7 Hz), 1.15 (3H, t, J=7 Hz), 3.05 (1H, dd, J=8, 14 Hz), 3.26 (1H,
d, d, J=7.5, 14 Hz), 3.30-3.46 (2H, m), 4.10 (2H, q, J=7 Hz), 4.38
(1H, t, J=8 Hz), 4.75 (1H, brs), 6.67-6.79 (5H, m), 7.05 (2H, d,
J=8.5 Hz), 7.18-7.26 (2H, m).
Reference Example 57
Ethyl 3-(4-hydroxyphenyl)-2-(pyrrole-1-yl)propionate
[1830] (a) Ethyl
3-(4-benzyloxyphenyl)-2-(pyrrole-1-yl)propionate
[1831] 1,4-dichloro-1,4-dimethoxybutane (3.30 g) was added to a
solution of ethyl 3-(4-benzyloxyphenyl)-2-aminopropionate (3.30 g)
in dichloromethane (80 ml) and then amberlyst A-21 (20 g) was added
to the mixture. The mixture was stirred at ambient temperature for
18 hours and the reaction mixture was filtered. The filtrate was
concentrated and the residue was purified via chromatography on a
silica gel column using ethyl acetate/hexane=1/5 as the eluant to
afford the desired compound (1.00 g) as a syrup.
[1832] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.19 (3H, t,
J=7 Hz), 3.19 (1H, dd, J=8.5, 14 Hz), 3.34 (1H, dd, J=7,14 Hz),
4.14 (2H, q, J=7 Hz), 4.68 (1H, dd, J=7, 8.5 Hz), 5.01 (2H, s),
6.15 (2H, t, J=2 Hz), 6.73 (2H, t, J=2 Hz), 6.84 (2H, d, J=8.5 Hz),
6.94 (2H, d, J=8.5 Hz), 7.28-7.43 (5H, m).
[1833] (b) Ethyl 3-(4-hydroxyphenyl)-2-(pyrrole-1-yl)propionate
[1834] In a similar manner to that described in Reference example
55(b), a reaction was carried out using ethyl
3-(4-benzyloxyphenyl)-2-(pyrrole-1-y- l)propionate (1.00 g)
obtained in Reference example 57(a) and palladium on carbon (5%,
0.12 g) and the reaction mixture was treated to afford the title
compound (0.71 g) as a syrup.
[1835] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.20 (3H, t,
J=7 Hz), 3.18 (1H, dd, J=8.5, 14 Hz), 3.33 (1H, dd, J=7, 14 Hz),
4.15 (2H, q, J=7 Hz), 4.67 (1H, dd, J=7, 8.5 Hz), 4.80 (1H, s),
6.14 (2H, t, J=2 Hz), 6.71 (2H, d, J=8.5 Hz), 6.72 (2H, d, J=2 Hz),
6.88 (2H, d, J=8.5 Hz).
Reference Example 58
Ethyl 2-(N,N-diethylamino)-3-(4-hydroxyphenyl)propionate
[1836] Acetic acid (0.3 ml) and acetaldehyde (0.5 ml) were added to
a solution of DL-tyrosine ethyl ester hydrochloride (491 mg) in
methanol (5 ml). To the mixture sodium cyanoborohydride (126 mg)
was added and the mixture was stirred at ambient temperature for 2
hours. At the end of this time the reaction mixture was
concentrated. The residue was partitioned between ethyl acetate and
water. The ethyl acetate layer was separated and washed with
aqueous sodium hydrogencarbonate solution and dried over anhydrous
magnesium sulfate and concentrated under reduced pressure. The
residue was purified via chromatography on a silica gel column
using methanol/dichloromethane=1/20 as the eluant to afford the
desired compound (420 mg) as a syrup.
[1837] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.02 (6H, t,
J=7 Hz), 1.16 (3H, t, J=7 Hz), 2.53 (2H, sextet, J=7 Hz), 2.79 (2H,
sextet, J=7 Hz), 2.81 (1H, dd, J=6, 13.5 Hz), 2.99 (1H, dd, J=9,
13.5 Hz), 3.55 (1H, dd, J=6, 9 Hz), 4.02-4.11 (2H, m), 6.72 (2H, d,
J=8.5 Hz), 7.02 (2H, d, J=8.5 Hz).
Reference Example 59
Ethyl
2-N-(t-butoxycarbonyl)ethylamino-3-(4-hydroxyphenyl)propionate
[1838] (a) Ethyl 2-ethylamino-3-(4-hydroxyphenyl)propionate
[1839] In a similar manner to that described in Reference example
9, a reaction was carried out using DL-tyrosine ethyl ester
hydrochloride (983 mg), acetaldehyde (0.26 ml) and sodium
cyanoborohydride (100 mg) and the reaction mixture was treated to
afford the desired compound (515 mg) as a syrup which was allowed
to stand to give crystals.
[1840] mp 87-89.degree. C.
[1841] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 1.08 (3H, t,
J=7 Hz), 1.18 (3H, t, J=7 Hz), 2.48-2.72 (2H, m), 2.82-2.96 (2H,
m), 3.50 (1H, t, J=7 Hz), 4.11 (2H, q, J=7 Hz), 6.68 (2H, d, J=8.5
Hz), 7.01 (2H, d, J=8.5 Hz).
[1842] (b) Ethyl
2-N-(t-butoxycarbonyl)ethylamino-3-(4-hydroxyphenyl)propi-
onate
[1843] Triethylamine (1 ml) was added dropwise to a solution of
ethyl 2-ethylamino-3-(4-hydroxyphenyl)propionate (569 mg), which is
the product of Reference example 59(a), and di-t-butylcarbonate
(785 mg) in dichloromethane (10 ml) in an ice bath. The mixture was
stirred at ambient temperature for 4 hours. At the end of this time
the reaction mixture was concentrated. The residue was partitioned
between ethyl acetate and water. The ethyl acetate layer was
separated and dried over anhydrous magnesium sulfate and
concentrated under reduced pressure. The residue was purified via
chromatography on a silica gel column using ethyl
acetate/hexane=1/2 as the eluant to afford the title compound (663
mg) as a syrup.
[1844] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm 0.90 (3H, br
t, J=7 Hz), 1.21-1.31 (3H. m), 1.45 (9H, s), 3.15-3.37 (1H, m),
3.08 (1H, dd, J=10, 14 Hz), 3.15-3.37 (1H, m), 3.24 (1H, dd, J=5,
14 Hz), 3.85-4.30 (3H, m), 6.76 (2H, br d, J=8.5 Hz), 7.00-7.11
(2H, m).
Reference Example 60
Ethyl
2-N-(t-butoxycarbonyl)propylamino-3-(4-hydroxyphenyl)propionate
[1845] (a) Ethyl 3-(4-hydroxyphenyl)-2-propylaminopropionate
[1846] In a similar manner to that described in Reference example
59(a), a reaction is carried out using DL-tyrosine ethyl ester
hydrochloride, propionaldehyde and sodium cyanoborohydride and the
reaction mixture is treated to afford the desired compound.
[1847] (b) Ethyl
2-N-(t-butoxycarbonyl)propylamino-3-(4-hydroxyphenyl)prop-
ionate
[1848] In a similar manner to that described in Reference example
59(b), a reaction is carried out using ethyl
3-(4-hydroxyphenyl)-2-propylaminoprop- ionate, which is the product
of reference example 60(a), and t-butyldicarbonate and the reaction
mixture is treated to afford the title compound.
Reference Example 61
2-(4-pyridine-2-ylbenzoylamino)ethanol
[1849] Triethylamine (0.14 ml) was added to a suspension of
4-pyridine-2-ylbenzoylchloride hydrochloride (254 mg) in
dichloromethane (2 ml). To the mixture a solution of ethanolamine
(0.060 ml) in dichloromethane (3ml) was added. This mixture was
stirred for 30 minutes. At the end of this time the reaction
mixture was concentrated and the residue was partitioned between
ethyl acetate and water. The ethyl acetate layer was separated and
washed with aqueous sodium chloride and dried over anhydrous
magnesium sulfate and concentrated to afford crystals. The crystals
were washed with isopropyl ether to afford the title compound (111
mg).
[1850] mp 86-88.degree. C.
[1851] .sup.1H-NMR (270 MHz, CDCl.sub.3): .delta. ppm
[1852] 2.52 (1H, t, J=4.5 Hz), 3.68 (2H, dt, J=5.0, 5.5 Hz),
3.88(2H, dt, J=4.5, 5.5 Hz), 6.68 (1H, br s), 7.24-7.33 (1H, m),
7.77-7.82 (1H, m), 7.90 (2H, d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz),
8.72 (1H, d, J=5 Hz).
Test Example
[1853] Action in Depressing Blood Glucose (Method 1)
[1854] Each compound, admixed with powder feed F-2 (Funabashi Farm)
was administered to hyperglycemic male KK mice each having a body
weight of 40 g or more at a rate of 0.01% (ca. 10 mg/kg/day) for
three days. Meanwhile, mice of a control group were fed with the
powder feed only. Then, a blood sample was collected from the
caudal vein of each mouse under no anesthesia and centrifuged. The
blood glucose in the plasma thus obtained was determined using
Glucoloader F (Product of A & T Co., Ltd.).
[1855] The blood glucose depression rate were estimated from the
following equation:
154 Blood glucose [(Blood glucose in Control group - depression
Blood glucose in administered group)/Blood glucose rate (%) = in
Control group] .times. 100
[1856] The results are summarized in Table 156.
155 TABLE 156 Rate of hypoglycemic Test Compound activity (%)
Compound of 43 Example 2 Compound of 15 Example 4 Compound of 22
Example 8 Compound of 64 Example 10 Compound of 42 Example 12
Compound of 64 Example 16 Compound of 68 Example 18 Compound of 17
Example 22 Compound of 35 Example 27 Compound of 20 Example 29
Compound of 18 Example 30 Compound of 21 Example 32 Compound of 22
Example 34 Compound of 20 Example 43 Compound of 37 Example 48
Compound of 20 Example 52 Compound of 16 Example 62 Compound of 23
Example 70 Compound of 60 Example 74 Compound of 50 Example 76
Compound of 53 Example 78 Compound of 50 Example 80 Compound of 32
Example 82 Compound of 66 Example 97 Compound of 57 Example 99
Compound of 51 Example 101 Compound of 48 Example 103 Compound of
73 Example 104 Compound of 38 Example 107 Compound of 38 Example
109 Compound of 70 Example 111 Compound of 64 Example 113 Compound
of 66 Example 115 Compound of 70 Example 117 Compound of 49 Example
119 Compound of 60 Example 121 Compound of 43 Example 123 Compound
of 54 Example 125 Compound of 56 Example 127 Compound of 49 Example
137 Compound of 23 Example 139 Compound of 27 Example 141 Compound
of 43 Example 143 Compound of 28 Example 145 Compound of 58 Example
152 These data show that the compounds of the present invention
exhibit excellent hypoglycemic activity.
Formulation Example
[1857] (1) Capsule
156 Compound of Example 2 10 mg Lactose 110 mg Corn starch 58 mg
Magnesium stearate 2 mg 180 mg
[1858] Powders of each component mentioned above were mixed and
passed through a sieve of 60 mesh (the standard of mesh was based
on Tyler). The mixed powder (180 mg) was used to fill a gelatin
capsule (No. 3) to give a capsule.
[1859] (2) Tablet
157 Compound of example 2 10 mg Lactose 85 mg Corn starch 34 mg
Finely crystallized cellulose 20 mg Magnesium stearate 1 mg 150
mg
[1860] Powders of each component shown above were mixed and
compression-molded to prepare a tablet (150 mg). If necessary the
tablet may be coated with sugar or film.
[1861] (3) Granule
158 Compound of Example 2 10 mg Lactose 839 mg Corn starch 150 mg
Hydroxypropyl cellulose 1 mg 1000 mg
[1862] Powders of each component shown above were mixed and wetted
with pure water, granulated using a basket type granulator and
dried to give a granule.
INDUSTRIAL APPLICABILITY
[1863] The amidocarboxylic acid derivatives, the pharmacologically
acceptable salts thereof and the pharmacologically acceptable
esters thereof of the present invention are useful as a preventive
agent and/or therapeutic agent for diabetes mellitus, hyperlipemia,
obesity, impaired glucose tolerance, insuline resistant
non-impaired glucose tolerance, hypertension, diabetic
complications, arteriosclerosis, gestational diabetes mellitus,
polycystic ovary syndrome, cell injury caused by atherosclerosis,
arthrosteitis, rheumatic arthritis, allergic diseases, asthma,
cancer, autoimmune diseases, pancreatitis, osteoporosis, cataracts,
etc.
* * * * *