U.S. patent application number 14/523296 was filed with the patent office on 2015-04-16 for 4-(4-pyridinyl)-benzamides and their use as rock activity modulators.
The applicant listed for this patent is AbbVie Deutschland GmbH & Co KG, AbbVie Inc.. Invention is credited to Dominique Bonafoux, Adrian Donald Hobson, Wilfried Hornberger, Michael F. Jarvis, Ryan Keddy, Helmut Mack, Bernhard K. Muller, Daryl Sauer, Steven L. Swann, Jr., Nicole Teusch, Anil Vasudevan.
Application Number | 20150105386 14/523296 |
Document ID | / |
Family ID | 39956743 |
Filed Date | 2015-04-16 |
United States Patent
Application |
20150105386 |
Kind Code |
A1 |
Mack; Helmut ; et
al. |
April 16, 2015 |
4-(4-PYRIDINYL)-BENZAMIDES AND THEIR USE AS ROCK ACTIVITY
MODULATORS
Abstract
The present invention relates to novel 4-(4-pyridyl)-benzamides
of the formula (I). The compounds I possess valuable therapeutic
properties and are suitable, in particular, for treating diseases
that respond to modulation of Rho kinases (ROCKs). R.sup.1 and
R.sup.2 are, independently of each other, hydrogen, hydroxy, cyano,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl,
C.sub.1-C.sub.8-alkoxy or C.sub.1-C.sub.8-haloalkoxy; R.sup.3,
R.sup.4, R.sup.5 and R.sup.6 are, independently of each other,
hydrogen, hydroxy, halogen, cyano, C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, C.sub.1-C.sub.8-alkoxy,
C.sub.1-C.sub.8-haloalkoxy, amino, C.sub.1-C.sub.8-alkylamino or
di-(C.sub.1-C.sub.8-alkyl)-amino; R.sup.7 is hydrogen,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl, aryl or
aryl-C.sub.1-C.sub.8-alkyl; R.sup.8 is a group of the formula
--X--W, where X is a single bond, C.sub.1-C.sub.4-alkylene or
C.sub.1-C.sub.4-alkylene-O--, where the alkylene group in the three
last-mentioned radicals may be linear or branched and may be partly
or fully halogenated and/or may be substituted by a hydroxyl group
and/or may be interrupted by an oxygen atom; and W is a cyclic
radical selected from phenyl and a 5- or 6-membered saturated,
partly unsaturated or aromatic heterocyclic ring which contains as
ring members 1, 2 or 3 heteroatoms selected O, S, and N and
optionally 1 or 2 carbonyl groups; R.sup.9 is a group of the
formula --Y--Z, where Z is hydrogen, halogen, OR.sup.11,
NR.sup.12R.sup.13, S(O).sub.m--R.sup.14, phenyl which may carry 1,
2, 3 or 4 substituents R.sup.15 or a 5- or 6-membered saturated,
partly unsaturated or aromatic heterocyclic ring; and Y is linear
or branched C.sub.1C.sub.4-alkylene which may be partly or fully
halogenated and/or may be substituted by a hydroxyl group and/or a
phenyl ring; or, in case Z is phenyl or the 5- or 6-membered
heterocyclic ring as defined above, Y can also be a single bond.
##STR00001##
Inventors: |
Mack; Helmut; (Ludwigshafen,
DE) ; Teusch; Nicole; (Ludwigshafen, DE) ;
Muller; Bernhard K.; (Ludwigshafen, DE) ; Hornberger;
Wilfried; (Ludwigshafen, DE) ; Jarvis; Michael
F.; (Vernon Hills, IL) ; Sauer; Daryl;
(Trevor, WI) ; Swann, Jr.; Steven L.; (San Diego,
CA) ; Bonafoux; Dominique; (Winthrop, MA) ;
Keddy; Ryan; (Beach Park, IL) ; Hobson; Adrian
Donald; (Shrewsbury, MA) ; Vasudevan; Anil;
(Union Grove, WI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AbbVie Deutschland GmbH & Co KG
AbbVie Inc. |
Ludwigshafen
North Chicago |
IL |
DE
US |
|
|
Family ID: |
39956743 |
Appl. No.: |
14/523296 |
Filed: |
October 24, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13868765 |
Apr 23, 2013 |
8895749 |
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14523296 |
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12675430 |
Jul 8, 2010 |
8445686 |
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PCT/EP08/61135 |
Aug 26, 2008 |
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13868765 |
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60966278 |
Aug 27, 2007 |
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Current U.S.
Class: |
514/235.5 ;
514/253.01; 514/318; 514/339; 514/341; 514/343; 514/357; 544/124;
544/360; 546/194; 546/275.1; 546/276.4; 546/277.4; 546/337 |
Current CPC
Class: |
A61P 25/28 20180101;
A61P 29/00 20180101; A61P 35/00 20180101; A61P 25/16 20180101; A61P
9/10 20180101; A61P 25/00 20180101; A61P 15/10 20180101; A61P 31/12
20180101; A61P 9/04 20180101; A61P 25/18 20180101; C07D 213/56
20130101; C07D 409/12 20130101; A61P 3/10 20180101; A61P 27/02
20180101; A61P 13/10 20180101; A61P 25/08 20180101; A61P 1/04
20180101; C07D 413/14 20130101; A61P 9/12 20180101; C07D 401/12
20130101; A61P 11/06 20180101; C07D 417/12 20130101; A61P 1/00
20180101; A61P 21/00 20180101; A61P 5/50 20180101; A61P 13/12
20180101; A61P 19/02 20180101; A61P 17/06 20180101; A61P 19/10
20180101; A61P 43/00 20180101; C07D 413/12 20130101; A61P 25/22
20180101; A61P 13/08 20180101; A61P 27/06 20180101; A61P 9/00
20180101; C07D 405/12 20130101; A61P 31/04 20180101; A61P 15/04
20180101; A61P 35/04 20180101; A61P 25/24 20180101; A61P 15/08
20180101; A61P 37/06 20180101; A61P 25/14 20180101 |
Class at
Publication: |
514/235.5 ;
546/337; 514/357; 546/277.4; 514/339; 546/276.4; 514/343; 544/124;
544/360; 514/253.01; 546/275.1; 514/341; 546/194; 514/318 |
International
Class: |
C07D 401/12 20060101
C07D401/12; C07D 213/56 20060101 C07D213/56 |
Claims
1. A compound of the formula I ##STR00044## or a physiologically
tolerated acid addition salt thereof, wherein R.sup.1 and R.sup.2
are, independently of each other, hydrogen, halogen, hydroxy,
cyano, C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl,
C.sub.1-C.sub.8-alkoxy or C.sub.1-C.sub.8-haloalkoxy; R.sup.3,
R.sup.4, R.sup.5 and R.sup.6 are, independently of each other,
hydrogen, hydroxy, halogen, cyano, C.sub.1-C.sub.8-haloalkyl,
C.sub.1-C.sub.8-alkoxy, C.sub.1-C.sub.8-haloalkoxy, amino,
C.sub.1-C.sub.8-alkylamino or di-(C.sub.1-C.sub.8-alkyl)-amino;
R.sup.7 is hydrogen, C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, C.sub.6-C.sub.14-aryl or
C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl; R.sup.8 is a group of
the formula X--W, where X is a single bond, linear or branched
C.sub.1-C.sub.4-alkylene or C.sub.1-C.sub.4-alkylene-O--, where the
alkylene group in the three last-mentioned radicals may be linear
or branched and may be partly or fully halogenated and/or may be
substituted by a hydroxyl group and/or may be interrupted by an
oxygen atom; and W is a cyclic radical selected from phenyl and a
5- or 6-membered saturated, partly unsaturated or aromatic
heterocyclic ring which contains as ring members 1, 2 or 3
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups, where phenyl and the heterocyclic ring may be fused to
phenyl, to a 5-, 6- or 7-membered saturated or partly unsaturated
carbocyclic ring, which may contain as ring members 1 or 2 carbonyl
groups, or to a 5- or 6-membered saturated, partly unsaturated or
aromatic heterocyclic ring which contains as ring members 1, 2 or 3
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups, where the fused phenyl ring, the fused carbocyclic ring and
the fused heterocyclic ring may for their part be fused to a phenyl
ring; and where the cyclic radical W may carry 1, 2, 3, 4 or 5
substituents R.sup.10; R.sup.9 is a group of the formula Y--Z,
where Z is hydrogen, halogen, OR.sup.11, NR.sup.12R.sup.13,
S(O).sub.m--R.sup.14, phenyl which may carry 1, 2, 3 or 4
substituents R.sup.15 or a 5- or 6-membered saturated, partly
unsaturated or aromatic heterocyclic ring which contains as ring
members 1, 2 or 3 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups and which may carry 1, 2, 3 or 4
substituents R.sup.15; and Y is linear or branched
C.sub.1-C.sub.4-alkylene which may be partly or fully halogenated
and/or may be substituted by a hydroxyl group and/or a phenyl ring;
or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring
as defined above, Y can also be a single bond; or R.sup.8 and
R.sup.9, together with the CH group to which they are bonded, form
a CH-bound saturated or partly unsaturated 5- or 6-membered
carbocyclic ring which may contain 1 or 2 carbonyl groups as ring
members or a saturated or partly unsaturated 5- or 6-membered
heterocyclic ring, where the heterocyclic ring contains 1 or 2
heteroatoms selected from O, S and N and optionally 1 carbonyl
group as ring members, where the carbocyclic ring and the
heterocyclic ring are fused to a phenyl ring or to a 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which contains as ring members 1, 2 or 3 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups, where the
carbocyclic ring and the heterocyclic ring and/or the ring fused
thereto may carry 1, 2 or 3 substituents R.sup.15, with the proviso
that in case the carbocyclic ring is fused to a phenyl ring, the
points of fusion are not in the 3,4-position, relative to the
1-position of the bond to the group NR.sup.7; each R.sup.10 is
independently selected from halogen, hydroxyl, SH, CN, nitro,
C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl,
C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, aryl,
heterocyclyl, aryl-C.sub.1-C.sub.4-alkyl,
aryl-C.sub.2-C.sub.4-alkenyl, aryl-C.sub.2-C.sub.4-alkynyl,
heterocyclyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy,
C.sub.2-C.sub.6-alkenyloxy, C.sub.2-C.sub.6-alkynyloxy,
C.sub.3-C.sub.6-cycloalkoxy, aryloxy, heterocyclyloxy,
aryl-C.sub.1-C.sub.4-alkoxy, aryloxy-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.6-alkylthio, C.sub.2-C.sub.6-alkenylthio,
C.sub.2-C.sub.6-alkynylthio, arylthio, heterocyclylthio,
aryl-C.sub.1-C.sub.4-alkylthio, arylthio-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.6-alkylsulfinyl, C.sub.2-C.sub.6-alkenylsulfinyl,
C.sub.2-C.sub.6-alkynylsulfinyl, arylsulfinyl,
heterocyclylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl,
C.sub.2-C.sub.6-alkenylsulfonyl, C.sub.2-C.sub.6-alkynylsulfonyl,
arylsulfonyl, heterocyclylsulfonyl, formyl,
C.sub.1-C.sub.6-alkylcarbonyl, C.sub.2-C.sub.6-alkenylcarbonyl,
C.sub.2-C.sub.6-alkynylcarbonyl, arylcarbonyl,
aryl-C.sub.1-C.sub.4-alkylcarbonyl, heterocyclylcarbonyl, carboxyl,
C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.2-C.sub.6-alkenyloxycarbonyl,
C.sub.2-C.sub.6-alkynyloxycarbonyl, aryloxycarbonyl,
aryl-C.sub.1-C.sub.4-alkoxycarbonyl, heterocyclyloxycarbonyl,
C.sub.1-C.sub.6-alkylcarbonyloxy,
C.sub.2-C.sub.6-alkenylcarbonyloxy,
C.sub.2-C.sub.6-alkynylcarbonyloxy, arylcarbonyloxy,
aryl-C.sub.1-C.sub.4-alkylcarbonyloxy, heterocyclylcarbonyloxy and
NR.sup.aR.sup.b, where R.sup.a and R.sup.b are independently
selected from H, C.sub.1-C.sub.6-alkyl, aryl, formyl,
C.sub.1-C.sub.6-alkylcarbonyl, arylcarbonyl and
C.sub.1-C.sub.6-alkylsulfonyl or, together with the nitrogen atom
to which they are bound, form a 4-, 5- or 6-membered saturated,
partly unsaturated or aromatic heterocyclic ring which may contain
as ring members 1 or 2 further heteroatoms selected from O, S and N
and/or 1 or 2 carbonyl groups, and where the heterocyclic ring may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; where aryl
in R.sup.10 is selected from phenyl and naphthyl, where
heterocyclyl is a saturated, partly unsaturated or aromatic 5 or
6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members, where the aliphatic and cycloaliphatic moieties in
the radicals R.sup.10 may be partly or fully halogenated and/or may
carry 1, 2 or 3 substituents selected from OH, CN,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.1-C.sub.4-alkylthio and C.sub.1-C.sub.4-haloalkylthio, where
the cycloaliphatic moieties may also carry 1, 2 or 3
C.sub.1-C.sub.6-alkyl substituents, where the aromatic and
heterocyclic moieties in the radicals R.sup.10 may be partly or
fully halogenated and/or may carry 1, 2, 3, 4 or 5 substituents
selected from OH, CN, C.sub.1-C.sub.6-alkyl,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylcarbonyl,
C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkylsulfonyl
and C.sub.1-C.sub.4-haloalkylsulfonyl; R.sup.11 is hydrogen,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl, phenyl or benzyl,
where the phenyl moiety in the two last-mentioned radicals may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; R.sup.12 and
R.sup.13, independently of each other, are hydrogen,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl,
C.sub.1-C.sub.8-hydroxyalkyl, C.sub.1-C.sub.8-alkylcarbonyl,
C.sub.1-C.sub.8-haloalkylcarbonyl, C.sub.1-C.sub.8-alkoxycarbonyl,
C.sub.1-C.sub.8-haloalkoxycarbonyl, C.sub.1-C.sub.8-alkylsulfinyl,
C.sub.1-C.sub.8-haloalkylsulfinyl, C.sub.1-C.sub.8-alkylsulfonyl,
C.sub.1-C.sub.8-haloalkylsulfonyl, C.sub.3-C.sub.8-cycloalkyl,
C.sub.3-C.sub.8-cycloalkyl-C.sub.1-C.sub.4-alkyl, phenyl, benzyl,
phenylcarbonyl, benzylcarbonyl, phenylsulfonyl or benzylsulfonyl,
where the phenyl moiety in the six last-mentioned radicals may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; or R.sup.12
and R.sup.13, together with the nitrogen atom to which they are
bound, form a 4-, 5- or 6-membered saturated, partly unsaturated or
aromatic heterocyclic ring which may contain as ring members 1 or 2
further heteroatoms selected from O, S and N and/or 1 or 2 carbonyl
groups, and where the heterocyclic ring may carry 1, 2 or 3
substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; R.sup.14 is
hydrogen, C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl, phenyl
or benzyl, where the phenyl moiety in the two last-mentioned
radicals may carry 1, 2 or 3 substituents selected from halogen,
hydroxyl, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; each
R.sup.15 is independently halogen, hydroxyl, CN, nitro,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.3-C.sub.6-cycloalkyl, aryl, aryl-C.sub.1-C.sub.4-alkyl,
aryloxy, aryl-C.sub.1-C.sub.4-alkoxy, heterocyclyl or
NR.sup.cR.sup.d, where R.sup.c and R.sup.d, independently of each
other, are selected from H, C.sub.1-C.sub.6-alkyl and aryl; where
aryl is selected from phenyl and naphthyl, where heterocyclyl is a
saturated, partly unsaturated or aromatic 5 or 6-membered
heterocyclic ring containing 1, 2, 3 or 4 heteroatoms selected from
O, S and N and optionally 1 or 2 carbonyl groups as ring members,
where the aromatic and heterocyclic moieties in the radicals
R.sup.15 may be partly or fully halogenated and/or may carry 1, 2,
3, 4 or 5 substituents selected from OH, CN, C.sub.1-C.sub.6-alkyl,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylcarbonyl,
C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkylsulfonyl
and C.sub.1-C.sub.4-haloalkylsulfonyl; and m is 0, 1 or 2; except
for
N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-(2-fluoro-5-methyl-pyridin-4-yl)--
benzamide.
2. The compound or salt as claimed in claim 1, wherein R.sup.1 and
R.sup.2 are, independently of each other, hydrogen, hydroxy, cyano,
C.sub.1-C.sub.8-haloalkyl, C.sub.1-C.sub.8-alkoxy or
C.sub.1-C.sub.8-haloalkoxy.
3. The compound or salt as claimed in claim 1, wherein R.sup.1 and
R.sup.2 are hydrogen, C.sub.1-C.sub.4-alkyl, fluorine or
chlorine.
4. The compound or salt as claimed in claim 1, wherein R.sup.3 and
R.sup.4 are independently selected from hydrogen, halogen,
C.sub.1-C.sub.4-alkyl and C.sub.1-C.sub.4-haloalkyl.
5. The compound or salt as claimed in claim 4, wherein one of
R.sup.3 and R.sup.4 is hydrogen and the other is hydrogen, halogen
or C.sub.1-C.sub.4-alkyl.
6. The compound or salt as claimed in claim 1, wherein R.sup.5 and
R.sup.6 are independently selected from hydrogen, halogen,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl and
C.sub.1-C.sub.4-alkoxy.
7. The compound or salt as claimed in claim 6, wherein one of
R.sup.5 and R.sup.6 is hydrogen and the other is hydrogen, halogen,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy.
8. The compound or salt as claimed in claim 1, wherein R.sup.7 is
hydrogen.
9. The compound or salt as claimed in claim 1, wherein X is a
single bond, CH.sub.2, CH(OH) or CH.sub.2CH.sub.2.
10. The compound or salt as claimed in claim 1, wherein W is
selected from phenyl, naphthyl, anthracenyl, phenanthrenyl,
indenyl, indanyl, dihydronaphthyl, tetralinyl, indolyl,
2,3-dihydroindolyl, indoxylyl, oxindolyl, indazolyl,
2,3-dihydroindazolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl,
cumaronyl (benzo[b]furanyl), 2,3-dihydrobenzofuranyl,
benzo-1,3-dioxyl, benzo-1,4-dioxanyl, benzoxazolyl,
2,3-dihydrobenzoxazolyl, benzo[b]thienyl, 2,3-dihydrobenzothienyl,
benzothiazolyl, 2,3-dihydrobenzothiazolyl, quinolinyl,
isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromenyl,
chromenonyl, isochromenyl, chromanyl, chromanonyl, isochromanyl,
acenaphthenyl, dihydroacenaphthenyl, fluorenyl, carbazolyl,
dibenzofuranyl, dibenzothienyl, acridinyl, carbazinyl (acridanyl),
phenazinyl, 9,10-dihydrophenazinyl, dibenzomorpholinyl
(phenoxazinyl), dibenzothiomorpholinyl (phenothiazinyl), where the
42 last-mentioned radicals are bonded via the phenyl moiety of the
fused system to the group X, a saturated, partly unsaturated or
aromatic 5- or 6-membered heterocyclic ring containing 1, 2, 3 or 4
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups as ring members and a saturated, partly unsaturated or
aromatic 5- or 6-membered heterocyclic ring containing 1 or 2
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups as ring members which is fused to a phenyl ring and which is
bonded via the heterocyclyl moiety of the fused system to the group
X, where the above radicals may carry 1, 2, 3, 4 or 5 substituents
R.sup.10 as defined in claim 1.
11. The compound or salt as claimed in claim 10, wherein W is
selected from phenyl, naphthyl, a 5- or 6-membered heteroaromatic
ring containing 1, 2 or 3 heteroatoms selected from O, S and N as
ring members and a saturated, partly unsaturated or aromatic 5- or
6-membered heterocyclic ring containing 1 or 2 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups as ring
members which is fused to a phenyl ring and which is bonded via the
heterocyclyl moiety of the fused system to the group X, where the
above radicals may carry 1, 2, 3, 4 or 5 substituents R.sup.10 as
defined in claim 1.
12. The compound or salt as claimed in claim 11, wherein W is
selected from phenyl, naphthyl, pyridyl, indolyl,
benzo-1,4-dioxanyl and pyrrolidinyl, where the above radicals may
carry 1, 2, 3, 4 or 5 substituents R.sup.10 as defined in claim
1.
13. The compound or salt as claimed in claim 1, wherein R.sup.10 is
selected from halogen, hydroxyl, C.sub.1-C.sub.6-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-haloalkylthio, phenyl, benzyl, phenoxy and
benzoxy.
14. The compound or salt as claimed in claim 1, wherein Y is
CH.sub.2, CH(OH), CH(phenyl) or CH.sub.2CH.sub.2.
15. The compound or salt as claimed in claim 1, wherein Z is
hydrogen, halogen, hydroxyl, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, phenyl or a group NR.sup.12R.sup.13,
where R.sup.12 and R.sup.13 are as defined in claim 1.
16. The compound or salt as claimed in claim 1, wherein R.sup.12
and R.sup.13, independently of each other, are hydrogen,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-alkylcarbonyl,
C.sub.1-C.sub.8-alkoxycarbonyl, C.sub.1-C.sub.8-alkylsulfonyl,
phenyl, benzyl, phenylcarbonyl, benzylcarbonyl, phenylsulfonyl or
benzylsulfonyl, where the phenyl moiety in the six last-mentioned
radicals may carry 1, 2 or 3 substituents selected from halogen,
hydroxyl, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; or R.sup.12
and R.sup.13, together with the nitrogen atom to which they are
bound, form a 4-, 5- or 6-membered saturated, partly unsaturated or
aromatic heterocyclic ring which may contain as ring members 1 or 2
further heteroatoms selected from O, S and N and/or 1 or 2 carbonyl
groups, and where the heterocyclic ring may carry 1, 2 or 3
substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy.
17. The compound or salt as claimed in claim 1, wherein R.sup.8 and
R.sup.9, together with the CH group to which they are bonded, form
a CH-bound saturated or partly unsaturated 5- or 6-membered
carbocyclic ring which may contain 1 or 2 carbonyl groups as ring
members or a saturated or partly unsaturated 5- or 6-membered
heterocyclic ring, where the heterocyclic ring contains 1 or 2
heteroatoms selected from O, S and N and optionally 1 carbonyl
group as ring members, where the carbocyclic ring and the
heterocyclic ring are fused to a phenyl ring where the carbocyclic
ring and the heterocyclic ring and/or the phenyl ring fused thereto
may carry 1, 2 or 3, preferably 1, substituents R.sup.15, with the
proviso that in case it is the carbocyclic ring which is fused to a
phenyl ring, the points of fusion are not in the 3,4-position,
relative to the 1-position of the bond to the group NR.sup.7.
18. A pharmaceutical composition containing at least one compound
of claim 1, or a physiologically tolerated acid addition salt
thereof, and at least one physiologically acceptable carrier or
auxiliary substance.
19-22. (canceled)
23. A method for treating a medical disorder comprising
administering an effective amount of a compound or salt as claimed
in claim 1 to a subject in need thereof, wherein the medical
disorder is selected from the group consisting of hypertension,
chronic and congestive heart failure, cardiac hypertrophy, chronic
renal failure, cerebral vasospasm, pulmonary hypertension, ocular
hypertension, cancer, tumor metastasis, asthma, male erectile
dysfunctions, female sexual dysfunctions, over-active bladder
syndrome, preterm labor, restenosis, atherosclerosis, neuronal
injury, in particular spinal cord injury, traumatic brain injury
and stroke, Parkinson's disease, Alzheimer disease, Huntington's
disease, spinal muscular atrophy, amyotrophic lateral sclerosis,
multiple sclerosis, encephalomyelitis, pain, rheumatoid arthritis,
osteoarthritis, osteoporosis, irritable bowel syndrome,
inflammatory bowel disease, HIV-1 encephalitis, diabetes, insulin
resistance, ischemic CNS disorders, vascular or AD type dementia,
glaucoma, psoriasis, retinopathy, benign prostatic hypertrophy,
psychiatric disorders, in particular depression, schizophrenia,
obsessive compulsive disorder and bipolar disorder, epilepsy and
seizure disorders, for decreasing ischemia-reperfusion injury,
myocardial infarct size and myocardial fibrosis, for the prevention
of graft failure and for treating diseases caused by viral and
bacterial infections.
24. A method for treating a medical disorder comprising
administering an effective amount of a compound or salt as claimed
in claim 1 to a subject in need thereof, wherein the medical
disorder is selected from the group consisting of pain, asthma,
cognitive dysfunctions, multiple sclerosis, cancer, rheumatoid
arthritis and injuries of the spinal cord.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to novel
4-(4-pyridyl)-benzamides. The compounds possess valuable
therapeutic properties and are suitable, in particular, for
treating diseases that respond to modulation of Rho kinases
(ROCKs).
[0002] An important large family of enzymes is the protein kinase
enzyme family. Currently, there are about 500 different known
protein kinases. Protein kinases serve to catalyze the
phosphorylation of an amino acid side chain in various proteins by
the transfer of the y-phosphate of the ATP-Mg.sup.2+ complex to
said amino acid side chain.
[0003] These enzymes control the majority of the signalling
processes inside cells, thereby governing cell function, growth,
differentiation and destruction (apoptosis) through reversible
phosphorylation of the hydroxyl groups of serine, threonine and
tyrosine residues in proteins. Studies have shown that protein
kinases are key regulators of many cell functions, including signal
transduction, transcriptional regulation, cell motility, and cell
division. Several oncogenes have also been shown to encode protein
kinases, suggesting that kinases play a role in oncogenesis. These
processes are highly regulated, often by complex intermeshed
pathways where each kinase will itself be regulated by one or more
kinases. Consequently, aberrant or inappropriate protein kinase
activity can contribute to the rise of disease states associated
with such aberrant kinase activity. Due to their physiological
relevance, variety and ubiquitousness, protein kinases have become
one of the most important and widely studied families of enzymes in
biochemical and medical research.
[0004] The protein kinase family of enzymes is typically classified
into two main subfamilies: Protein Tyrosine Kinases and Protein
SerineThreonine Kinases, based on the amino acid residue they
phosphorylate. The serinethreonine kinases (PSTK), includes cyclic
AMP- and cyclic GMP-dependent protein kinases, calcium- and
phospholipid-dependent protein kinase, calcium- and
calmodulin-dependent protein kinases, casein kinases, cell division
cycle protein kinases and others. These kinases are usually
cytoplasmic or associated with the particulate fractions of cells,
possibly by anchoring proteins. Aberrant protein serinethreonine
kinase activity has been implicated or is suspected in a number of
pathologies such as rheumatoid arthritis, psoriasis, septic shock,
bone loss, many cancers and other proliferative diseases.
[0005] Accordingly, serinethreonine kinases and the signal
transduction pathways which they are part of are important targets
for drug design. The tyrosine kinases phosphorylate tyrosine
residues. Tyrosine kinases play an equally important role in cell
regulation. These kinases include several receptors for molecules
such as growth factors and hormones, including epidermal growth
factor receptor, insulin receptor, platelet derived growth factor
receptor and others. Studies have indicated that many tyrosine
kinases are transmembrane proteins with their receptor domains
located on the outside of the cell and their kinase domains on the
inside. Much work is also under progress to identify modulators of
tyrosine kinases as well.
[0006] A major signal transduction systems utilized by cells is the
RhoA-signalling pathways. RhoA is a small GTP binding protein that
can be activated by several extracellular stimuli such as growth
factor, hormones, mechanic stress, osmotic change as well as high
concentration of metabolite like glucose. RhoA activation involves
GTP binding, conformation alteration, post-translational
modification (geranylization and farnesylation) and activation of
its intrinsic GTPase activity. Activated RhoA is capable of
interacting with several effector proteins including ROCKs (Rho
kinase) and transmit signals into cellular cytoplasm and
nucleus.
[0007] Rho kinase is found in two isoforms encoded by two different
genes of ROCK, ROCK 1 (also known as ROCK.beta. or p160-ROCK) and
ROCK 2 (also known as ROCK.alpha.). Both ROCK 1 and ROCK 2 contain
an amino-terminal catalytic kinase domain, a central coiled-coil
domain of about 600 amino acids, and a carboxyl-terminal pleckstrin
homology (PH) domain that is split by a cysteine-rich region.
RhoGTP interacts with the Cterminal portion of the central
coiled-coil domain and activates the kinase activity of ROCK.
[0008] Thus, ROCK1 and 2 constitute a family of serinethreonine
kinases that can be activated by RhoA-GTP complex via physical
association. Activated ROCKs phosphorylate a number of substrates
and play important roles in pivotal cellular functions. The
substrates for ROCKs include myosin binding subunit of myosin light
chain phosphatase (MBS, also named MYPT1), adducin, moesin, myosin
light chain (MLC), LIM kinase as well as transcription factor FHL.
The phosphorylation of theses substrates modulate the biological
activity of the proteins and thus provide a means to alter cell's
response to external stimuli. One well documented example is the
participation of ROCK in smooth muscle contraction. Upon
stimulation by phenylephrine, smooth muscle from blood vessels
contracts. Studies have shown that phenylephrine stimulates
alpha-adrenergic receptors and leads to the activation of RhoA.
Activated RhoA in turn stimulates kinase activity of ROCK1 and
which in turn phosphorylates MBS. Such phosphorylation inhibits the
enzyme activity of myosin light chain phosphatase and increases the
phosphorylation of myosin light chain itself by a calcium-dependent
myosin light chain kinase (MLCK) and consequently increases the
contractility of myosin-actin bundle, leading to smooth muscle
contraction. This phenomenon is also sometimes called calcium
sensitization. In addition to smooth muscle contraction, ROCKs have
also been shown to be involved in cellular functions including
apoptosis, cell migration, transcriptional activation, fibrosis,
cytokinesis, inflammation and cell proliferation. Moreover, in
neurons ROCK plays a critical role in the inhibition of axonal
growth by myelin-associated inhibitory factors such as
myelin-associated glycoprotein (MAG). ROCK-activity also mediates
the collapse of growth cones in developing neurons. Both processes
are thought to be mediated by ROCK-induced phosphorylation of
substrates such as LIM kinase and myosin light chain phosphatase,
resulting in increased contractility of the neuronal actin-myosin
system.
[0009] Abnormal activation of the RhoROCK pathway has been observed
in various disorders (.sup.1Wettschureck, N., Offermanns, S.,
RhoRho-kinase mediated signaling in physiology and pathophysiology.
J. Mol. Med. 80, 2002, 629-638; .sup.2Muller, B. K., Mack, H.,
Teusch, N., Rho kinase, a promising drug target for neurological
discorders. Nat. Drug Discov. Rev. 4, 2005, 387-398; .sup.3Hu, E,
Lee, D., ROCK inhibitors as potential therapeutic agents for
cardiovascular diseases. Curr. Opin. Investig. Drugs. 4, 2003,
1065-1075). As already mentioned, ROCKs phosphorylate the myosin
binding subunit of myosin light chain (MLC) phosphatase (MLCP),
resulting in increased myosin phosphorylation and actin-myosin
contraction (Somlyo, A. P., Somlyo, A. V., Ca2+ sensitivity of
smooth muscle and nonmuscle myosin II: modulated by G proteins,
kinases, and myosin phosphatase. Physiol. Rev. 83, 2003,
1325-1358). Examples of disease states related with abnormal
RhoROCK activity, in particular with vasospasm activity, include
cardiovascular diseases such as hypertension (.sup.9Satoh S.,
Kreutz R., Wilm C., Ganten D., Pfitzer G., Augmented
agonist-induced Ca.sup.2+-sensitization of coronary artery
contraction in genetically hypertensive rats. Evidence for altered
signal transduction in the coronary smooth muscle cells. J. Clin.
Invest. 94, 1994, 1397-1403; .sup.10Mukai, Y., Shimokawa, H.,
Matoba, T., Kandabashi, T., Satoh, S., Hiroki, J., Kaibuchi, K.,
Takeshita, A., Involvement of Rho-kinase in hypertensive vascular
disease: a novel therapeutic target in hypertension. FASEB J. 15,
2001, 1062-1064; .sup.11Uehata, M., Ishizaki, T., Satoh, H., Ono,
T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui,
J., Maekawa, M., Narumiya, S., Calcium sensitization of smooth
muscle mediated by a Rho-associated protein kinase in hypertension.
Nature 389, 1997, 990-994; .sup.12Masumoto, A., Hirooka, Y.,
Shimokawa, H., Hironaga, K., Setoguchi, S., Takeshita, A., Possible
involvement of Rhokinase in the pathogenesis of hypertension in
humans. Hypertension 38, 2001, 1307-1310), chronic and congestive
heart failure (.sup.18Fuster, V., Badimon, L., Badimon, J J,
Chesebro, J H, The pathogenesis of coronary artery disease and the
acute coronary syndromes (2). N Engl J Med 326, 1992, 310-318;
.sup.19Shimokawa, H., Cellular and molecular mechanisms of coronary
artery spasm: lessons from animal models. Jpn Circ J 64, 2000,
1-12; .sup.20Shimokawa, H., Morishige, K., Miyata, K., Kandabashi,
T., Eto, Y., Ikegaki, I., Asano, T., Kaibuchi, K., Takeshita, A.,
Longterm inhibition of Rho-kinase induces a regression of
arteriosclerotic coronary lesions in a porcine model in vivo.
Cardiovasc Res 51, 2001, 169-177; .sup.21Utsunomiya, T., Satoh, S.,
Ikegaki, I., Toshima, Y., Asano, T., Shimokawa, H., Antianginal
effects of hydroxyfasudil, a Rho-kinase inhibitor, in a canine
model of effort angina. Br J Pharmacol 134, 201, 1724-1730),
cardiac hypertrophy (.sup.40Hoshijima, M., Sah, V. P., Wang, Y.,
Chien, K. R., Brown, J. H., The low molecular weight GTPase Rho
regulates myofibril formation and organization in neonatal rat
ventricular myocytes. Involvement of Rho kinase. J Biol Chem 273,
1998, 7725-77230; .sup.41Sah, V. P., Hoshijima, M., Chien, K. R.,
Brown, J. H., Rho is required for Galphaq and alpha1-adrenergic
receptor signal-637 ing in cardiomyocytes. Dissociation of Ras and
Rho pathways. J Biol Chem 271, 1996, 31185-1190; .sup.42Kuwahara,
K., Saito, Y., Nakagawa, O., Kishimoto, I., Harada, M., Ogawa, E.,
Miyamoto, Y., Hamanaka, I., Kajiyama, N., Takahashi, N., Izumi, T.,
Kawakami, R., Tamura, N., Ogawa, Y., Nakao, K., The effects of the
selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic
response in neonatal rat cardiacmyocytes-possible involvement of
Rho/ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett 452,
1999, 314-318), chronic renal failure (.sup.7Sharpe, C. C., Hendry,
B., M. Signaling: focus on Rho in renal disease. J. Am. Soc.
Nephrol. 14, 2003, 261-264), cerebral vasospasm after subarachnoid
bleeding (.sup.13Shibuya, M., Suzuki, Y., Sugita, K., Saito, I.,
Sasaki, T., Takakura, K., Okamoto, S., Kikuchi, H., Takemae, T.,
Hidaka, H., Dose escalation trial of a novel calcium antagonist,
AT877, in patients 636 with aneurysmal subarachnoid haemorrhage.
Acta Neurochir (Wien) 107, 1990, 11-15; .sup.14Shibuya, M., Suzuki,
Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Nagata, I.,
Kikuchi, H., Takemae, T., Hidaka, H., et. al, Effect of AT877 on
cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
Results of a prospective placebo-controlled double-blind trial. J
Neurosurg 76, 1992, 571-577; .sup.15Sato, M., Tani, E., Fujikawa,
H., Kaibuchi, K., Involvement of Rhokinase-mediated phosphorylation
of myosin light chain in enhancement of cerebral vasospasm. Circ
Res 87, 2000, 195-200; .sup.16Miyagi, Y., Carpenter, R. C., Meguro,
T., Parent, A. D., Zhang, J. H., Upregulation of rho A and rho
kinase messenger RNAs in the basilar artery of a rat model of
subarachnoid hemorrhage. J Neurosurg 93, 2000, 471-476;
.sup.17Tachibana, E., Harada, T., Shibuya, M. Saito, K., Takayasu,
M., Suzuki, Y., Yoshida, J., Intra-arterial infusion of fasudil
hydrochloride for treating vasospasm following subarachnoid
haemorrhage. Acta Neurochir (Wien) 141, 1999, 13-19), pulmonary
hypertension (.sup.5Sylvester, J. T., The tone of pulmonary smooth
muscle: ROK and Rho music? Am. J. Physiol. Lung Cell. Mol. Physiol.
287, 2004, L624-L630) and ocular hypertension (.sup.34Honjo, M.,
Inatani, M., Kido, N., Sawamura, T., Yue, B. Y., Honda, Y.,
Tanihara H., Effects of protein kinase inhibitor, HA1077, on
intraocular pressure and outflow facility in rabbit eyes. Arch
Ophthalmol 119, 2001, 1171-1178; .sup.35Rao, P. V, Deng, P. F.,
Kumar, J. Epstein, D. L., Modulation of aqueous humor outflow
facility by the Rho kinase-specific inhibitor Y-27632. Invest
Ophthalmol V is Sci 42, 2001, 1029-1037). Further diseases related
to abnormal RhoROCK activity are cancer (.sup.6Aznar, S.,
Fernandez-Valeron, P., Espina, C., Lacal, J. C., Rho GTPases:
potential candidates for anticancer therapy. Cancer Lett. 206,
2004, 181-191; .sup.43Yin, L. et al., Fasudil inhibits vascular
endothelial growth factor-induced angiogenesis in vitro and in
vivo. Mol Cancer Ther 5, 2007, 1517-25; .sup.44Itoh, K., Yoshioka,
K., Akedo, H., Uehata, M., Ishizaki, T., Narumiya, S., An essential
part for Rho-associated kinase in the transcellular invasion of
tumor cells. Nat Med 5, 1999, 221-225; .sup.45Genda, T. Sakamoto,
M., Ichida, T., Asakura, H., Kojiro, M., Narumiya, S., Hirohashi,
S., Cell motility mediated by rho and Rho-associated protein kinase
plays a critical role inintrahepatic metastasis of human
hepatocellular carcinoma. Hepatology 30, 1999, 1027-1036;
.sup.46Somlyo, A. V., Bradshaw, D., Ramos, S., Murphy, C., Myers,
C. E., Somlyo, A. P., Rho-kinase inhibitor retards migration and in
vivo dissemination of human prostate cancer cells. Biochem Biophys
Res Commun 269, 2000, 652-659), asthma (.sup.24Roberts, J. A.,
Raeburn, D., Rodger, I. W., Thomson, N. C., Comparison of in vivo
airway responsiveness and in vitro smooth muscle sensitivity to
methacholine in man. Thorax 39; 1984, 837-843; .sup.25Chiba, Y.,
Misawa, M., Characteristics of muscarinic cholinoceptors in airways
of antigen-induced airway hyperresponsive rats. Comp Biochem
Physiol C Pharmacol Toxicol Endocrinol 111, 1995, 351-357;
.sup.26Chiba, Y., Takada, Y., Miyamoto, S., MitsuiSaito, M.,
Karaki, H., Misawa, M., Augmented acetylcholine-induced, Rho
mediated Ca.sup.2+ sensitization of bronchial smooth muscle
contraction in antigen-induced airway hyperresponsive rats. Br J
Pharmacol 127, 1999, 597-600; .sup.27Chiba, Y., Sakai, H. Misawa,
M., Augmented acetylcholine-induced translocation of RhoA in
bronchial smooth muscle from antigen-induced airway hyperresponsive
rats. BrJ Pharmacol 133, 2001, 886-890; .sup.28lizuka, K., Shimizu,
Y., Tsukagoshi, H., Yoshii, A., Harada, T. Dobashi, K., Murozono,
T., Nakazawa, T., Mori, M., Evaluation of Y-27632, a rho-kinase
inhibitor, as a bronchodilator in guinea pigs. Eur J Pharmacol 406,
2000, 273-279), male erectile dysfunctions (.sup.8Andersson, K. E.,
Hedlund, P., New directions for erectile dysfunction therapies.
Int. J. Impot. Res. 14 (Suppl. 1), 2002, S82-S92; .sup.32Chitaley,
K., Wingard, C. J., Clinton Webb, R., Branam, H., Stopper, V. S.,
Lewis, R. W., Mills, T. M., Antagonism of Rho-kinase stimulates rat
penile erection via a nitric oxideindependent pathway. Nat Med 7,
2001, 119-122; .sup.33 Mills, T. M., Chitaley, K., Wingard, C. J.,
Lewis, R. W., Webb, R. C., Effect of Rho-kinase inhibition on
vasoconstriction in the penile circulation. J Appl Physiol 91,
2001, 1269-1273), female sexual dysfunction, over-active bladder
syndrome (.sup.64Peters, S. L. et al., Rho kinase: a target for
treating urinary bladder dysfunction? Trends Pharmacol Sci. 27,
2006, 492-7) and preterm labor (.sup.29Niiro, N., Nishimura, J.,
Sakihara, C., Nakano, H., Kanaide, H., Up-regulation of rho A and
rho-kinase mRNAs in the rat myometrium during pregnancy. Biochem
Biophys Res Commun 230, 1997, 356-359; .sup.30Tahara, M.,
Morishige, K., Sawada, K., Ikebuchi, Y., Kawagishi, R., Tasaka, K.,
Murata, Y., RhoARho-kinase cascade is involved in oxytocin-induced
rat uterine contraction. Endocrinology 143, 2002, 920-929;
.sup.31Kupittayanant, S., Burdyga, T., Wray, S., The effects of
inhibiting Rho-associated kinase with Y-27632 on force and
intracellular calcium in human myometrium. Pflugers Arch. 443,
2001, 112-114).
[0010] Inhibitors of ROCKs have been suggested for use in the
treatments of a variety of diseases. They include cardiovascular
diseases such as hypertension (see above .sup.9-12), chronic and
congestive heart failure.sup.18-21, and cardiac
hypertrophy.sup.40-42, chronic renal failure.sup.7, furthermore
cerebral vasospasm after subarachnoid bleeding.sup.13-17, pulmonary
hypertension.sup.5 and ocular hypertension.sup.34, 35. In addition,
because of their muscle relaxing properties, they are also suitable
for asthma.sup.24-28, male erectile dysfunctions.sup.8, 32, 33,
female sexual dysfunction and over-active bladder syndrome and
preterm labor.sup.29-31. Several recent studies have reported the
beneficial effects of ROCK inhibitors in ischemia--reperfusion and
myocardial infarction. In these studies, the ROCK inhibitors
Y-27632 and fasudil were shown to decrease ischemiareperfusion
injury, myocardial infarct size, and myocardial fibrosis in
response to experimental myocardial infarction (MI) and in a rat
model of chronic hypertension induced congestive heart failure (see
above .sup.18-21 and .sup.22Masumoto, A., Mohri, M., Shimokaw, a
H., Urakami, L., Usui, M., Takeshita, A., Suppression of coronary
artery spasm by the rho-kinase inhibitor fasudil in patients with
vasospastic angina. Circulation 105, 2002, 1545-1547;
.sup.23Shimokawa, H., linuma, H., Kishida, H., et al., Antianginal
effect of fasudil, a Rho-kinase inhibitor, in patients with stable
effort angina: a multicenter study (abstract). Circulation 104
[Suppl II], 2001, 11691; .sup.36Morishige K, Shimokawa H, Eto Y,
Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K,
Takeshita A, Adenovirus-mediated transfer of dominant-negative
rho-kinase induces a regression of coronary arteriosclerosis in
pigs in vivo. Arterioscler Thromb Vasc Biol 21, 2001, 548-554;
.sup.37Kandabashi T, Shimokawa H, Mukai Y, Matoba T, Kunihiro I,
Morikawa K, Ito M, Takahashi S, Kaibuchi K, Takeshita A,
Involvement of rho-kinase in agonists-induced contractions of
arteriosclerotic human arteries. Arterioscler Thromb Vasc Biol 22,
2002, 243-248; .sup.38Liu M W, Roubin G S, King SB 3.sup.rd,
Restenosis after coronary angioplasty. Potential biologic
determinants and role of intimal hyperplasia. Circulation 79, 1989,
1374-1387; .sup.39Shibata R, Kai H, Seki Y, Kato S, Morimatsu M,
Kaibuchi K, Imaizumi T, Role of Rho-associated kinase in neointima
formation after vascular injury. Circulation 103, 2001,
284-289).
[0011] Additionally, ROCKs can interact with other signalling
pathways resulting in inhibition of phosphoinositide-3 kinase
(PI-3K), endothelial nitric oxide synthase (eNOS) pathways, and
activation of plasminogen activator inhibitor-1 (PAI-1) which may
contribute to endothelial dysfunction like restenosis and
atherosclerosis. Thus ROCK inhibitors have been suggested for the
treatment of restenosis and atherosclerosis (see above.sup.38-39
and Iwasaki, H. et al., High glucose induces plasminogen activator
inhibitor-1 expression through Rho/Rho-kinase-mediated NF-kappaB
activation in bovine aortic endothelial cells. Atherosclerosis,
2007, Jan 31).
[0012] Vascular intimal thickening in vein grafts after surgery is
the major cause of late graft failure. In a study with the ROCK
inhibitor fasudil, the intimal thickening and vascular smooth
muscle cell (VSMC) proliferation was significantly suppressed,
whereas VSMC apoptosis was enhanced in the weeks following the
procedure, suggesting that ROCK inhibitors can be used as a
therapeutic agent for the prevention of graft failure.sup.36-39,
67.
[0013] Injury to the adult vertebrate brain and spinal cord
activates ROCKs, thereby causing neurodegeneration and inhibition
of neuroregeneration like neurite growth and sprouting (.sup.56
Bito, H., Furuyashiki, T., Ishihara, H., Shibasaki, Y., Ohashi, K.,
Mizuno, K., Maekawa, M., Ishizaki, T., Narumiya, S., A critical
role for a Rho-associated kinase, p160ROCK, in determining axon
outgrowth in mammalian CNS neurons. Neuron 26, 2000, 431-441).
Inhibition of ROCKs results in induction of new axonal growth,
axonal rewiring across lesions within the CNS, accelerated
regeneration and enhanced functional recovery after acute neuronal
injury in mammals (spinal-cord injury, traumatic brain injury) (see
above .sup.64 and .sup.60Hara, M. et al., Protein kinase inhibition
by fasudil hydrochloride promotes neurological recovery after
spinal cord injury in rats. J. Neurosurg. Spine 93, 94-101;
.sup.61Fournier, A. E., Takizawa, B. T. & Strittmatter, S. M.,
ROCK inhibition enhances axonal regeneration in the injured CNS. J.
Neurosci. 23, 2003, 1416-1423; .sup.62Sung, J. K. et al., A
possible role of RhoARho-kinase in experimental spinal cord injury
in rat. Brain Res. 959, 2003, 29-38; .sup.63Tanaka, H. et al.,
Cytoplasmic p21 (Cip1/WAF1) enhances axonal regeneration and
functional recovery after spinal cord injury in rats. Neuroscience
127, 2004, 155-164). ROCK inhibitors are therefore likely to be
useful for regenerative (recovery) treatment of CNS disorders such
as spinal cord injury, acute neuronal injury (stroke, traumatic
brain injury) (.sup.52Okamura N et al., Vasodilator effects of
fasudil, a Rho-kinase inhibitor, on retinal arterioles in
strokeprone spontaneously hypertensive rats. J Ocul Pharmacol Ther.
23, 2007, 207-12; .sup.53Yagita Y et al., Rho-kinase activation in
endothelial cells contributes to expansion of infarction after
focal cerebral ischemia. J Neurosci Res. 85, 2007, 2460-9),
Parkinson's disease, Alzheimer disease (.sup.54Pedrini S et al.,
Modulation of statin-activated shedding of Alzheimer APP ectodomain
by ROCK. PLoS Med. 2, 2005, 18; .sup.55Burton A., NSAIDS and
Alzheimer's disease: its only Rock and Rho. Lancet Neurol. 3(1),
2004, 6) and other neurodegenerative disorders. Other
neurodegenetarive disorders for which ROCK inhibitors are expected
to be useful are Huntington's disease (Shao J, Welch W J,
Diprospero N A, Diamond M I. Phosphorylation of profilin by ROCK1
regulates polyglutamine aggregation. Mol Cell Biol. 2008 September;
28(17):5196-208; Shao J, Welch W J, Diamond M I. ROCK and PRK-2
mediate the inhibitory effect of Y-27632 on polyglutamine
aggregation. FEBS Lett. 2008 May 28; 582(12):1637-42), spinal
muscular atrophy (Bowerman M, Shafey D, Kothary R. Smn depletion
alters profilin II expression and leads to upregulation of the
RhoAROCK pathway and defects in neuronal integrity. J Mol.
Neurosci. 2007; 32(2):120-31) and amyotrophic lateral sclerosis.
Inhibition of the RhoROCK pathway has also proved to be efficacious
in other animal models of neurodegeneration like stroke.sup.52, 53
and in inflammatory and demyelinating diseases like multiple
sclerosis (.sup.51Sun X et al., The selective Rho-kinase inhibitor
Fasudil is protective and therapeutic in experimental autoimmune
encephalomyelitis. J Neuroimmunol. 180, 2006, 126-34), acute and
chronic pain (.sup.57Inoue, M. et al., Initiation of neuropathic
pain requires lysophosphatidic acid receptor signaling. Nature Med.
10, 2004, 712-718; .sup.58Ramer, L. M., Borisoff, J. F. &
Ramer, M. S., Rho-kinase inhibition enhances axonal plasticity and
attenuates cold hyperalgesia after dorsal rhizotomy. J. Neurosci.
24, 2004, 10796-10805; .sup.59Tatsumi, S. et al., Involvement of
Rho-kinase in inflammatory and neuropathic pain through
phosphorylation of myristoylated alanine-rich Ckinase substrate
(MARCKS). Neuroscience 131, 2005, 491-498).
[0014] ROCK inhibitors have been shown to possess anti-inflammatory
properties by decreased cytokine release, e.g. TNF.alpha.. Thus
they can be used as treatment for neuroinflammatory diseases such
as stroke, multiple sclerosis, Alzheimer's disease, Parkinson's
disease, amyotrophic lateral sclerosis and inflammatory pain, as
well as other inflammatory diseases such as rheumatoid arthritis,
osteoarthritis, osteoporosis, asthma, irritable bowel syndrome, or
inflammatory bowel disease (.sup.70Segain J. P., Rho kinase
blockade prevents inflammation via nuclear factor kappa B
inhibition: evidence in Crohn's disease and experimental colitis.
Gastroenterology. 124(5), 2003, 1180-7). In addition, recent
reports have demonstrated that inhibition of ROCK results in
disruption of inflammatory cell chemotaxis as well as inhibition of
smooth muscle contraction in models of pulmonary inflammation
associated with asthma. Therefore, the inhibitors of the Rho/ROCK
pathway should be useful for the treatment of asthma (see above
.sup.51 and .sup.47Kawaguchi A, Ohmori M, Harada K, Tsuruoka S,
Sugimoto K, Fujimura A., The effect of a Rho kinase inhibitor
Y-27632 on superoxide production, aggregation and adhesion inhuman
polymorphonuclear leukocytes. Eur J Pharmacol 403, 2000, 203-208;
.sup.48Lou Z, Billadeau D D, Savoy D N, Schoon R A, Leibson P. J.,
A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of
cytotoxic lymphocytes. J Immunol 167, 2001, 5749-5757;
.sup.49Vicente-Manzanares M, Cabrero J R, Rey M, Perez-Martinez M,
Ursa A, Itoh K, Sanchez-Madrid F., A role for the Rho-p160 Rho
coiled-coil kinase axis in the chemokine stromal cell-derived
factor-1alpha-induced lymphocyte actomyosinand microtubular
organization and chemotaxis. J Immunol 168, 2002, 400-410;
.sup.50Thorlacius K et al., Protective effect of fasudil, a
Rho-kinase inhibitor, on chemokine expression, leukocyte
recruitment, and hepatocellular apoptosis in septic liver injury. J
Leukoc Biol. 79, 2006, 923-31).
[0015] Since ROCK inhibitors reduce cell proliferation and cell
migration, they could be useful in treating cancer and tumor
metastasis.sup.6, 43-46. ROCK inhibitors can also be beneficial in
diseases with impaired blood brain barrier function, e.g. HIV-1
encephalitis (.sup.71Persidski Y et al., Rho-mediated regulation of
tight junctions during monocyte migration across the blood-brain
barrier in HIV-1 encephalitis (HIVE). Blood. 107, 2006, 4770-4780)
and Alzheimer's disease (.sup.72Man S-M et al., Peripheral T cells
overexpress MIP-1.alpha. to enhance its transendothelial migration
in Alzheimer's disease. Neurobiol. Of Aging 28, 2007, 485-496).
[0016] Furthermore, there is evidence suggesting that ROCK
inhibitors suppress cytoskeletal rearrangement upon virus invasion,
thus they also have potential therapeutic value in anti-viral and
anti-bacterial applications (.sup.69Favoreel H W, Cytoskeletal
rearrangements and cell extensions induced by the US3 kinase of an
alphaherpesvirus are associated with enhanced spread. Proc Natl
Acad Sci USA. 102(25), 2006, 8990-5).
[0017] ROCKs have been reported to interfere with insulin
signalling through serine phosphorylation of insulin receptor
substrate-1 (IRS-1), in cultured VSMC. Activation of RhoAROCK was
observed in skeletal muscles and aortic tissues of Zucker obese
rats. Inhibition of ROCK, by fasudil for 4 weeks, reduced blood
pressure, corrected glucose and lipid metabolism, improved insulin
signalling and endothelial dysfunction. In another experiment
administration of high dose fasudil completely suppressed the
development of diabetes, obesity, and dyslipidemia and increased
serum adiponectin levels in OLETF rats. ROCK inhibitors may
therefore be useful for the treatment of insulin resistance and
diabetes (see above .sup.67 and .sup.65Nakamura Y et al., Marked
increase of insulin gene transcription by suppression of the
RhoRho-kinase pathway. Biochem Biophys Res Commun. 350(1), 2006,
68-73; .sup.66Kikuchi Y et al., A Rho-kinase inhibitor, fasudil,
prevents development of diabetes and nephropathy in
insulin-resistant diabetic rats. J Endocrinol. 192(3), 2007,
595-603; .sup.68Goyo A et al., The Rho-kinase inhibitor, fasudil,
attenuates diabetic nephropathy in streptozotocin-induced diabetic
rats. Eur J. Pharmacol. 568(1-3), 2007, 242-7).
[0018] The ROCK inhibitor Fasudil increased cerebral blood flow and
was neuroprotective under CNS ischemic conditions. ROCK inhibitors
are expected to be useful for the treatment of ischemic CNS
disorders and may therefore improve functional outcome in patients
suffering from stroke, vascular or AD type dementia.sup.52, 53.
[0019] Due to the efficacy of Y-27632 and fasudil in animal models
of epileptogenesis, of ROCK inhibitors have been suggested for the
use in the treatments of epilepsy and seizure disorders (Inan S Y,
Buyukafsar K. Antiepileptic effects of two Rho-kinase inhibitors,
Y-27632 and fasudil, in mice. Br. J. Pharmacol. advance online
publication, 9 Jun. 2008; doi:10.1038bjp.2008.225)
[0020] ROCK inhibitors are also expected to be useful for the
treatment of glaucoma.sup.34, 35, psoriasis, retinopathy and benign
prostatic hypertrophy.
[0021] As ROCK's have been implicated in neuronal morphogenesis,
connectivity, and plasticity in general, they are expected to be
useful for the treatment of psychiatric disorders, e.g. maior
depression, schizophrenia, obsessive compulsive disorder and
bipolar disorders.
[0022] ROCK inhibitors have been described in the prior art, e.g.
in WO 2007026920, WO 2005074643 and WO 2004016597. However, their
affinity and selectivity or their pharmacological profile is not
yet satisfactory.
SUMMARY OF THE INVENTION
[0023] It is an object of the present invention to provide
compounds which have a high affinity and selectivity for the ROCKs,
thus allowing the treatment of disorders associated with
inappropriate ROCK activity.
[0024] This object is surprisingly achieved by means of compounds
of the formula I
##STR00002##
wherein [0025] R.sup.1 and R.sup.2 are, independently of each
other, hydrogen, hydroxy, halogen, cyano, C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, C.sub.1-C.sub.8-alkoxy or
C.sub.1-C.sub.8-haloalkoxy; [0026] R.sup.3, R.sup.4, R.sup.5 and
R.sup.6 are, independently of each other, hydrogen, hydroxy,
halogen, cyano, C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl,
C.sub.1-C.sub.8-alkoxy, C.sub.1-C.sub.8-haloalkoxy, amino,
C.sub.1-C.sub.8-alkylamino or di-(C.sub.1-C.sub.3-alkyl)-amino;
[0027] R.sup.7 is hydrogen, C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, aryl or aryl-C.sub.1-C.sub.8-alkyl;
[0028] R.sup.8 is a group of the formula X--W, where [0029] X is a
single bond, C.sub.1-C.sub.4-alkylene or
C.sub.1-C.sub.4-alkylene-O--, where the alkylene group in the three
last-mentioned radicals may be linear or branched and may be partly
or fully halogenated and/or may be substituted by a hydroxyl group
and/or may be interrupted by an oxygen atom; and [0030] W is a
cyclic radical selected from phenyl and a 5- or 6-membered
saturated, partly unsaturated or aromatic heterocyclic ring which
contains as ring members 1, 2 or 3 heteroatoms selected from O, S
and N and optionally 1 or 2 carbonyl groups, where phenyl and the
heterocyclic ring may be fused to phenyl, to a 5- or 6-membered
saturated or partly unsaturated carbocyclic ring, which may contain
as ring members 1 or 2 carbonyl groups, or to a 5- or 6-membered
saturated, partly unsaturated or aromatic heterocyclic ring which
contains as ring members 1, 2 or 3 heteroatoms selected from O, S
and N and optionally 1 or 2 carbonyl groups, where the fused phenyl
ring, the fused carbocyclic ring and the fused heterocyclic ring
may for their part be fused to a phenyl ring; and where the cyclic
radical W may carry 1, 2, 3, 4 or 5 substituents R.sup.10; [0031]
R.sup.9 is a group of the formula Y--Z, where [0032] Z is hydrogen,
halogen, OR.sup.11, NR.sup.12R.sup.13, S(O).sub.m--R.sup.14, phenyl
which may carry 1, 2, 3 or 4 substituents R.sup.15 or a 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which contains as ring members 1, 2 or 3 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups and which may
carry 1, 2, 3 or 4 substituents R.sup.15; and [0033] Y is linear or
branched C.sub.1-C.sub.4-alkylene which may be partly or fully
halogenated and/or may be substituted by a hydroxyl group and/or a
phenyl ring; or, in case Z is phenyl or the 5- or 6-membered
heterocyclic ring as defined above, Y can also be a single bond;
[0034] or R.sup.8 and R.sup.9, together with the CH group to which
they are bonded, form a CH-bound saturated or partly unsaturated 5-
or 6-membered carbocyclic ring which may contain 1 or 2 carbonyl
groups as ring members or a saturated or partly unsaturated 5- or
6-membered heterocyclic ring, where the heterocyclic ring contains
1 or 2 heteroatoms selected from O, S and N and optionally 1
carbonyl group as ring members, where the carbocyclic ring and the
heterocyclic ring are fused to a phenyl ring or to a 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which contains as ring members 1, 2 or 3 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups, where the
carbocyclic ring and the heterocyclic ring and/or the ring fused
thereto may carry 1, 2 or 3 substituents R.sup.15, with the proviso
that in case the carbocyclic ring is fused to a phenyl ring, the
points of fusion are not in the 3,4-position, relative to the
1-position of the bond to the group NR.sup.7; [0035] each R.sup.10
is independently selected from halogen, hydroxyl, SH, CN, nitro,
C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl,
C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, aryl,
heterocyclyl, aryl-C.sub.1-C.sub.4-alkyl,
aryl-C.sub.2-C.sub.4-alkenyl, aryl-C.sub.2-C.sub.4-alkynyl,
heterocyclyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy,
C.sub.2-C.sub.6-alkenyloxy, C.sub.2-C.sub.6-alkynyloxy,
C.sub.3-C.sub.6-cycloalkoxy, aryloxy, heterocyclyloxy,
aryl-C.sub.1-C.sub.4alkoxy, aryloxy-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.6-alkylthio, C.sub.2-C.sub.6-alkenylthio,
C.sub.2-C.sub.6-alkynylthio, arylthio, heterocyclylthio,
aryl-C.sub.1-C.sub.4-alkylthio, arylthio-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.6-alkylsulfinyl, C.sub.2-C.sub.6-alkenylsulfinyl,
C.sub.2-C.sub.6-alkynylsulfinyl, arylsulfinyl,
heterocyclylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl,
C.sub.2-C.sub.6-alkenylsulfonyl, C.sub.2-C.sub.6-alkynylsulfonyl,
arylsulfonyl, heterocyclylsulfonyl, formyl,
C.sub.1-C.sub.6-alkylcarbonyl, C.sub.2-C.sub.6-alkenylcarbonyl,
C.sub.2-C.sub.6-alkynylcarbonyl, arylcarbonyl,
aryl-C.sub.1-C.sub.4-alkylcarbonyl, heterocyclylcarbonyl, carboxyl,
C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.2-C.sub.6-alkenyloxycarbonyl,
C.sub.2-C.sub.6-alkynyloxycarbonyl, aryloxycarbonyl,
aryl-C.sub.1-C.sub.4-alkoxycarbonyl, heterocyclyloxycarbonyl,
C.sub.1-C.sub.6-alkylcarbonyloxy,
C.sub.2-C.sub.6-alkenylcarbonyloxy,
C.sub.2-C.sub.6-alkenylcarbonyloxy, arylcarbonyloxy,
aryl-C.sub.1-C.sub.4-alkylcarbonyloxy, heterocyclylcarbonyloxy and
NR.sup.aR.sup.b, where R.sup.a and R.sup.b are independently
selected from H, C.sub.1-C.sub.6-alkyl, aryl, formyl,
C.sub.1-C.sub.6-alkylcarbonyl, arylcarbonyl and
C.sub.1-C.sub.6-alkylsulfonyl or, together with the nitrogen atom
to which they are bound, form a 4-, 5- or 6-membered saturated,
partly unsaturated or aromatic heterocyclic ring which may contain
as ring members 1 or 2 further heteroatoms selected from O, S and N
and/or 1 or 2 carbonyl groups, and where the heterocyclic ring may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0036] where
aryl is selected from phenyl and naphthyl, [0037] where
heterocyclyl is a saturated, partly unsaturated or aromatic 5 or
6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members, [0038] where the aliphatic and cycloaliphatic
moieties in the radicals R.sup.10 may be partly or fully
halogenated and/or may carry 1, 2 or 3 substituents selected from
OH, CN, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.1-C.sub.4-alkylthio and C.sub.1-C.sub.4-haloalkylthio, where
the cycloaliphatic moieties may also carry 1, 2 or 3
C.sub.1-C.sub.6-alkyl substituents, [0039] where the aromatic and
heterocyclic moieties in the radicals R.sup.10 may be partly or
fully halogenated and/or may carry 1, 2, 3, 4 or 5 substituents
selected from OH, CN, C.sub.1-C.sub.6-alkyl,
C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylcarbonyl,
C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkylsulfonyl
and C.sub.1-C.sub.4-haloalkylsulfonyl; [0040] R.sup.11 is hydrogen,
C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8-haloalkyl, phenyl or benzyl,
where the phenyl moiety in the two last-mentioned radicals may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0041]
R.sup.12 and R.sup.13, independently of each other, are hydrogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-haloalkyl,
C.sub.1-C.sub.8-hydroxyalkyl, C.sub.1-C.sub.8-alkylcarbonyl,
C.sub.1-C.sub.3-haloalkylcarbonyl, C.sub.1-C.sub.8-alkoxycarbonyl,
C.sub.1-C.sub.8-haloalkoxycarbonyl, C.sub.1-C.sub.8-alkylsulfinyl,
C.sub.1-C.sub.8-haloalkylsulfinyl, C.sub.1-C.sub.8-alkylsulfonyl,
C.sub.1-C.sub.8-haloalkylsulfonyl, C.sub.3-C.sub.8-cycloalkyl,
C.sub.3-C.sub.8-cycloalkyl-C.sub.1-C.sub.4-alkyl, phenyl, benzyl,
phenylcarbonyl, benzylcarbonyl, phenylsulfonyl or benzylsulfonyl,
where the phenyl moiety in the six last-mentioned radicals may
carry 1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0042] or
R.sup.12 and R.sup.13, together with the nitrogen atom to which
they are bound, form a 4-, 5- or 6-membered saturated, partly
unsaturated or aromatic heterocyclic ring which may contain as ring
members 1 or 2 further heteroatoms selected from O, S and N and/or
1 or 2 carbonyl groups, and where the heterocyclic ring may carry
1, 2 or 3 substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0043]
R.sup.14 is hydrogen, C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, phenyl or benzyl, where the phenyl
moiety in the two last-mentioned radicals may carry 1, 2 or 3
substituents selected from halogen, hydroxyl,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0044] each
R.sup.15 is independently halogen, hydroxyl, CN, nitro,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.3-C.sub.6cycloalkyl, aryl, aryl-C.sub.1-C.sub.4-alkyl,
aryloxy, aryl-C.sub.1-C.sub.4-alkoxy, heterocyclyl or
NR.sup.cR.sup.d, where Rc and R.sup.d, independently of each other,
are selected from H, C.sub.1-C.sub.6-alkyl and aryl; [0045] where
aryl is selected from phenyl and naphthyl, [0046] where
heterocyclyl is a saturated, partly unsaturated or aromatic 5 or
6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members, [0047] where the aromatic and heterocyclic moieties
in the radicals R.sup.15 may be partly or fully halogenated and/or
may carry 1, 2, 3, 4 or 5 substituents selected from OH, CN,
C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio,
C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl,
C.sub.1-C.sub.4-alkylsulfonyl and
C.sub.1-C.sub.4-haloalkylsulfonyl; and [0048] m is 0, 1 or 2; and
physiologically tolerated acid addition salts thereof, except for
the compound I wherein R.sup.1 is F, R.sup.3 is methyl, R.sup.2,
R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are H, R.sup.8 is
3-chlorophenyl and R.sup.9 is hydroxymethyl
(N-[1-(3-chlorophenyl)-2-hydroxyethyl]-4-(2-fluoro-5-methyl-pyridin-4-yl)-
-benzamide).
[0049] The present invention therefore relates to compounds of the
general formula I and to their physiologically tolerated acid
addition salts.
[0050] The present invention also relates to a pharmaceutical
composition which comprises at least one compound of the formula I
and/or at least one physiologically tolerated acid addition salt of
I, and at least one physiologically acceptable carrier and/or at
least one auxiliary substance.
[0051] The present invention also relates to a method for treating
disorders which respond to influencing by ROCK ligands, said method
comprising administering an effective amount of at least one
compound of the formula I and/or at least one physiologically
tolerated acid addition salt of I to a subject in need thereof.
[0052] The present invention further relates to the use of a
compound of the formula I and/or physiologically tolerated acid
addition salts thereof, for preparing a medicament for the
treatment of a medical disorder susceptible to treatment with a
ROCK ligand.
[0053] Preferably, the compounds of the invention are ROCK
inhibitors.
DETAILED DESCRIPTION OF THE INVENTION
[0054] The remarks made in the following with respect to preferred
aspects of the invention, e.g. to preferred meanings of the
variables of compound I, to preferred compounds I and to preferred
embodiments of the method or the use according to the invention,
apply in each case on their own or to combinations thereof.
[0055] The diseases which respond to the influencing of ROCKs, in
particular to ROCK inhibitors, include, in particular,
cardiovascular diseases such as hypertension, chronic and
congestive heart failure, cardiac hypertrophy, restenosis, chronic
renal failure, atherosclerosis, asthma, male erectile dysfunctions,
female sexual dysfunction, over-active bladder syndrome,
neuroinflammatory diseases such as stroke, multiple sclerosis,
Alzheimer's disease, Parkinson's disease, amyotrophic lateral
sclerosis and inflammatory pain, as well as other inflammatory
diseases such as rheumatoid arthritis, irritable bowel syndrome, or
inflammatory bowel disease. In addition, based on their neurite
outgrowth inducing effects, ROCK inhibitors can be used as drugs
for neuronal regeneration, inducing new axonal growth and axonal
rewiring across lesions within the CNS. ROCK inhibitors are
therefore useful for regenerative (recovery) treatment of CNS
disorders such as spinal cord injury, acute neuronal injury
(stroke, traumatic brain injury), Parkinson's disease, Alzheimer
disease and other neurodegenerative disorders, such as, in
particular, Huntington's disease, spinal muscular atrophy, and
amyotrophic lateral sclerosis. Since ROCK inhibitors reduce cell
proliferation and cell migration, they could be useful in treating
cancer and tumor metastasis. Furthermore, there is evidence
suggesting that ROCK inhibitors suppress cytoskeletal rearrangement
upon virus invasion, thus they also have potential therapeutic
value in anti-viral and anti-bacterial applications. ROCK
inhibitors may also be useful for the treatment of insulin
resistance and diabetes. ROCK inhibitors may furthermore be useful
for the treatment of ischemic CNS disorders, vascular or AD type
dementia, glaucoma, psoriasis, retinopathy, benign prostatic
hypertrophy, psychiatric disorders, in particular depression,
schizophrenia, obsessive compulsive disorder and bipolar disorder,
epilepsy and seizure disorders, for decreasing ischemia-reperfusion
injury, myocardial infarct size and myocardial fibrosis, and for
the prevention of graft failure. Accordingly, the compounds I of
the present invention can be used for treating the above-listed
disorders. More preferably, they are used for treating pain,
asthma, Alzheimer's disease, multiple sclerosis, rheumatoid
arthritis and spinal cord injuries.
[0056] Provided the compounds of the formula I of a given
constitution may exist in different spatial arrangements, for
example if they possess one or more centers of asymmetry,
polysubstituted rings or double bonds, or as different tautomers,
it is also possible to use enantiomeric mixtures, in particular
racemates, diastereomeric mixtures and tautomeric mixtures,
preferably, however, the respective essentially pure enantiomers,
diastereomers and tautomers of the compounds of formula I and/or of
their salts.
[0057] Particularly, the carbon atom of the CH group carrying
R.sup.8 and R.sup.9 may have (S) or (R) configuration in case these
are different. In one preferred embodiment, this carbon atom has
following absolute configuration (which, in the CIP terminology,
can be R or S, depending on the respective radicals XW and YZ):
##STR00003##
[0058] It is likewise possible to use physiologically tolerated
salts of the compounds of the formula I, especially acid addition
salts with physiologically tolerated acids. Examples of suitable
physiologically tolerated organic and inorganic acids are
hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric
acid, C.sub.1-C.sub.4-alkylsulfonic acids, such as methanesulfonic
acid, aromatic sulfonic acids, such as benzenesulfonic acid and
toluenesulfonic acid, oxalic acid, maleic acid, fumaric acid,
lactic acid, tartaric acid, citric acid, adipic acid and benzoic
acid. Other utilizable acids are described in Fortschritte der
Arzneimittelforschung [Advances in drug research], Volume 10, pages
224 ff., Birkha user Verlag, Basel and Stuttgart, 1966.
[0059] The organic moieties mentioned in the above definitions of
the variables are--like the term halogen--collective terms for
individual listings of the individual group members. The prefix
C.sub.n--C.sub.m indicates in each case the possible number of
carbon atoms in the group.
[0060] The term halogen denotes in each case fluorine, bromine,
chlorine or iodine, in particular fluorine, chlorine or
bromine.
[0061] C.sub.1-C.sub.4-Alkyl is a straight-chain or branched alkyl
group having from 1 to 4 carbon atoms. Examples of an alkyl group
are methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl,
iso-butyl or tert-butyl. C.sub.1-C.sub.2 Alkyl is methyl or ethyl,
C.sub.1-C.sub.3 alkyl is additionally n-propyl or isopropyl.
[0062] C.sub.1-C.sub.6-Alkyl is a straight-chain or branched alkyl
group having from 1 to 6 carbon atoms. Examples include
C.sub.1-C.sub.4-alkyl as mentioned above and also pentyl,
1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,
1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,
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,
1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and
1-ethyl-2-methylpropyl.
[0063] C.sub.1-C.sub.8-Alkyl is a straight-chain or branched alkyl
group having from 1 to 8 carbon atoms. Examples include
C.sub.1-C.sub.6-alkyl as mentioned above and also heptyl, octyl,
2-ethylhexyl and positional isomers thereof.
[0064] Haloalkyl is an alkyl group wherein a part or all of the
hydrogen atoms are replaced by a halogen atom, in particular by
fluorine and/or chlorine. Preferably, haloalkyl is fluorinated
alkyl. Fluorinated C.sub.1-C.sub.8-alkyl is a straight-chain or
branched alkyl group having from 1 to 8, preferably 1 to 6
(=fluorinated C.sub.1-C.sub.6-alkyl), especially 1 to 4 carbon
atoms (=fluorinated C.sub.1-C.sub.4-alkyl), in particular 1 to 3
carbon atoms (=fluorinated C.sub.1-C.sub.3-alkyl), wherein at least
one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a
fluorine atom such as in fluoromethyl, difluoromethyl,
trifluoromethyl, (R)-1-fluoroethyl, (S)-1-fluoroethyl,
2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, (R)-1-fluoropropyl,
(S)-1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl,
1,1-difluoropropyl, 2,2-difluoropropyl, 3,3-difluoropropyl,
3,3,3-trifluoropropyl, (R)-2-fluoro-1-methylethyl,
(S)-2-fluoro-1-methylethyl, (R)-2,2-difluoro-1-methylethyl,
(S)-2,2-difluoro-1-methylethyl, (R)-1,2-difluoro-1-methylethyl,
(S)-1,2-difluoro-1-methylethyl, (R)-2,2,2-trifluoro-1-methylethyl,
(S)-2,2,2-trifluoro-1-methylethyl, 2-fluoro-1-(fluoromethyl)ethyl,
1-(difluoromethyl)-2,2-difluoroethyl,
1-(trifluoromethyl)-2,2,2-trifluoroethyl,
1-(trifluoromethyl)-1,2,2,2-tetrafluoroethyl, (R)-1-fluorobutyl,
(S)-1-fluorobutyl, 2-fluorobutyl, 3-fluorobutyl, 4-fluorobutyl,
1,1-difluorobutyl, 2,2-difluorobutyl, 3,3-difluorobutyl,
4,4-difluorobutyl, 4,4,4-trifluorobutyl, and the like.
[0065] C.sub.1-C.sub.8-Alkoxy is a straight-chain or branched alkyl
group having from 1 to 8, preferably 1 to 6
(.dbd.C.sub.1-C.sub.6-alkoxy), in particular 1 to 4 carbon atoms
(.dbd.C.sub.1-C.sub.4-alkoxy), which is bound to the remainder of
the molecule via an oxygen atom. Examples include methoxy, ethoxy,
n-propoxy, isopropoxy, n-butoxy, 2-butoxy, iso-butoxy, tert.-butoxy
pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy,
2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy,
1,2-dimethylpropoxy, n-hexyloxy, 1-methylpentyloxy,
2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy,
1,1-dimethylbutyloxy, 1,2-dimethylbutyloxy, 1,3-dimethylbutyloxy,
2,2-dimethylbutyloxy, 2,3-dimethylbutyloxy, 3,3-dimethylbutyloxy,
1-ethylbutyloxy, 2-ethylbutyloxy, 1,1,2-trimethylpropoxy,
1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy,
1-ethyl-2-methylpropoxy, heptyloxy and octyloxy.
[0066] Haloalkoxy is an alkoxy group wherein a part or all of the
hydrogen atoms are replaced by a halogen atom, in particular by
fluorine and/or chlorine. Preferably, haloalkoxy is fluorinated
alkoxy. Fluorinated C.sub.1-C.sub.8-alkoxy is a straight-chain or
branched alkoxy group having from 1 to 8, preferably 1 to 6
(=fluorinated C.sub.1-C.sub.6-alkoxy), in particular 1 to 4 carbon
atoms (=fluorinated C.sub.1-C.sub.4-alkoxy), wherein at least one,
e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a
fluorine atoms such as in fluoromethoxy, difluoromethoxy,
trifluoromethoxy, (R)-1-fluoroethoxy, (S)-1-fluoroethoxy,
2-fluoroethoxy, 1,1-difluoroethoxy, 2,2-difluoroethoxy,
2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy,
(R)-1-fluoropropoxy, (S)-1-fluoropropoxy, (R)-2-fluoropropoxy,
(S)-2-fluoropropoxy, 3-fluoropropoxy, 1,1-difluoropropoxy,
2,2-difluoropropoxy, 3,3-difluoropropoxy, 3,3,3-trifluoropropoxy,
(R)-2-fluoro-1-methylethoxy, (S)-2-fluoro-1-methylethoxy,
(R)-2,2-difluoro-1-methylethoxy, (S)-2,2-difluoro-1-methylethoxy,
(R)-1,2-difluoro-1-methylethoxy, (S)-1,2-difluoro-1-methylethoxy,
(R)-2,2,2-trifluoro-1-methylethoxy,
(S)-2,2,2-trifluoro-1-methylethoxy,
2-fluoro-1-(fluoromethyl)ethoxy,
1-(difluoromethyl)-2,2-difluoroethoxy, (R)-1-fluorobutoxy,
(S)-1-fluorobutoxy, 2-fluorobutoxy, 3-fluorobutoxy, 4-fluorobutoxy,
1,1-difluorobutoxy, 2,2-difluorobutoxy, 3,3-difluorobutoxy,
4,4-difluorobutoxy, 4,4,4-trifluorobutoxy, and the like.
[0067] C.sub.1-C.sub.8-Hydroxyalkyl is a straight-chain or branched
alkyl group having from 1 to 8, preferably 1 to 6
(.dbd.C.sub.1-C.sub.6-hydroxyalkyl), especially 1 to 4 carbon atoms
(.dbd.C.sub.1-C.sub.4-hydroxyalkyl), in particular 1 to 3 carbon
atoms (.dbd.C.sub.1-C.sub.3-hydroxyalkyl), wherein one of the
hydrogen atoms is replaced by a hydroxy group, such as in
2-hydroxyethyl or 3-hydroxypropyl.
[0068] C.sub.1-C.sub.6-Alkoxy-C.sub.1-C.sub.6-alkyl is a
straight-chain or branched alkyl group having from 1 to 6,
especially 1 to 4 carbon atoms, in particular 1 to 3 carbon atoms,
wherein one of the hydrogen atoms is replaced by a
C.sub.1-C.sub.6-alkoxy group, such as in methoxymethyl,
2-methoxyethyl, ethoxymethyl, 3-methoxypropyl, 3-ethoxypropyl and
the like.
[0069] C.sub.1-C.sub.6-Alkoxy-C.sub.1-C.sub.6-alkoxy is a
straight-chain or branched alkyl group having from 1 to 6,
especially 1 to 4 carbon atoms, in particular 1 to 3 carbon atoms,
wherein one of the hydrogen atoms is replaced by a
C.sub.1-C.sub.6-alkoxy group, such as in 2-methoxyethoxy,
ethoxymethoxy, 2-ethoxyethoxy, 3-methoxypropoxy, 3-ethoxypropoxy
and the like.
[0070] C.sub.1-C.sub.8-Alkylcarbonyl is a straight-chain or
branched alkyl group having from 1 to 8, preferably 1 to 6
(.dbd.C.sub.1-C.sub.6-alkylcarbonyl), especially 1 to 4 carbon
atoms (.dbd.C.sub.1-C.sub.4-alkylcarbonyl), in particular 1 to 3
carbon atoms (.dbd.C.sub.1-C.sub.3-alkylcarbonyl), which is bound
via a carbonyl group (CO) to the remainder of the molecule.
Examples for C.sub.1-C.sub.3-alkylcarbonyl are acetyl and
propionyl. Examples for C.sub.1-C.sub.4-alkylcarbonyl are, apart
those mentioned for C.sub.1-C.sub.3-alkylcarbonyl, butylcarbonyl,
sec-butylcarbony, isobutylcarbonyl and tert-butylcarbonyl. Examples
for C.sub.1-C.sub.6-alkylcarbonyl are, apart those mentioned for
C.sub.1-C.sub.4-alkylcarbonyl, pentylcarbonyl and hexylcarbonyl.
Examples for C.sub.1-C.sub.8-alkylcarbonyl are, apart those
mentioned for C.sub.1-C.sub.6-alkylcarbonyl, heptylcarbonyl,
octylcarbonyl and 2-ethylhexylcarbonyl.
[0071] Haloalkylcarbonyl is an alkylcarbonyl group wherein a part
or all of the hydrogen atoms are replaced by a halogen atom, in
particular by fluorine and/or chlorine. Preferably,
haloalkylcarbonyl is fluorinated alkylcarbonyl. Fluorinated
C.sub.1-C.sub.6-alkylcarbonyl is a straight-chain or branched alkyl
group having from 1 to 6 (=fluorinated
C.sub.1-C.sub.6-alkylcarbonyl), especially 1 to 4 carbon atoms
(=fluorinated C.sub.1-C.sub.4-alkylcarbonyl), in particular 1 to 3
carbon atoms (=fluorinated C.sub.1-C.sub.3-alkylcarbonyl), wherein
one of the hydrogen atoms is replaced by a carbonyl group (CO) and
wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3,
or 4 of the hydrogen atoms are replaced by a fluorine atom, such as
in trifluoroacetyl and 3,3,3-trifluoropropionyl.
[0072] C.sub.1-C.sub.3-Alkylcarbonyloxy is a straight-chain or
branched alkyl group having from 1 to 8, preferably 1 to 6
(.dbd.C.sub.1-C.sub.6-alkylcarbonyloxy), especially 1 to 4 carbon
atoms (.dbd.C.sub.1-C.sub.4-alkylcarbonyloxy), in particular 1 to 3
carbon atoms (.dbd.C.sub.1-C.sub.3-alkylcarbonyloxy), which is
bound via a carbonyloxy group (C(O)--O) to the remainder of the
molecule. Examples for C.sub.1-C.sub.3-alkylcarbonyloxy are
acetyloxy and propionyloxy. Examples for
C.sub.1-C.sub.4-alkylcarbonyl are, apart those mentioned for
C.sub.1-C.sub.3-alkylcarbonyl, butylcarbonyloxy,
sec-butylcarbonyoxy, isobutylcarbonyloxy and tert-butylcarbonyloxy.
Examples for C.sub.1-C.sub.6-alkylcarbonyl are, apart those
mentioned for C.sub.1-C.sub.4-alkylcarbonyl, pentylcarbonyloxy and
hexylcarbonyloxy. Examples for C.sub.1-C.sub.8-alkylcarbonyl are,
apart those mentioned for C.sub.1-C.sub.6-alkylcarbonyl,
heptylcarbonyloxy, octylcarbonyloxy and
2-ethylhexylcarbonyloxy.
[0073] Haloalkylcarbonyloxy is an alkylcarbonyloxy group wherein a
part or all of the hydrogen atoms are replaced by a halogen atom,
in particular by fluorine and/or chlorine. Preferably,
haloalkylcarbonyloxy is fluorinated alkylcarbonyloxy Fluorinated
C.sub.1-C.sub.6-alkylcarbonyloxy is a straight-chain or branched
alkyl group having from 1 to 6 (=fluorinated
C.sub.1-C.sub.6-alkylcarbonyloxy), especially 1 to 4 carbon atoms
(=fluorinated C.sub.1-C.sub.4-alkylcarbonyloxy), in particular 1 to
3 carbon atoms (=fluorinated C.sub.1-C.sub.3-alkylcarbonyloxy),
which is bound via a carbonyloxy group (CO--O--) to the remainder
of the molecule and wherein at least one of the remaining hydrogen
atoms, e.g. 1, 2, 3, or 4 of the hydrogen atoms are replaced by a
fluorine atom, such as in trifluoroacetyloxy and
3,3,3-trifluoropropionyloxy.
[0074] C.sub.1-C.sub.6-Alkylcarbonylamino is a straight-chain or
branched alkyl group having from 1 to 6, especially 1 to 4 carbon
atoms (.dbd.C.sub.1-C.sub.4-alkylcarbonylamino), in particular 1 to
3 carbon atoms (.dbd.C.sub.1-C.sub.3-alkylcarbonylamino), which is
bound via a carbonylamino group (CO--NH--) to the remainder of the
molecule, such as in acetamido (acetylamino) (CH.sub.3CONH--) and
propionamido (CH.sub.3CH.sub.2CONH--).
[0075] Haloalkylcarbonylamino is an alkylcarbonylamino group
wherein a part or all of the hydrogen atoms are replaced by a
halogen atom, in particular by fluorine and/or chlorine.
Preferably, haloalkylcarbonylamino is fluorinated
alkylcarbonylamino. Fluorinated C.sub.r C.sub.6-alkylcarbonylamino
is a straight-chain or branched alkyl group having from 1 to 6
(=fluorinated C.sub.1-C.sub.6-alkylcarbonylamino), especially 1 to
4 carbon atoms (=fluorinated C.sub.1-C.sub.4-alkylcarbonylamino),
in particular 1 to 3 carbon atoms (=fluorinated
C.sub.1-C.sub.3-alkylcarbonylamino), which is bound via a
carbonylamino group (CO--NH--) to the remainder of the molecule and
wherein at least one of the remaining hydrogen atoms, e.g. 1, 2, 3,
or 4 of the hydrogen atoms are replaced by a fluorine atom, such as
in trifluoroacetylamino and 3,3,3-trifluoropropionylamino.
[0076] C.sub.1-C.sub.8-Alkoxycarbonyl is a straight-chain or
branched alkoxy group having from 1 to 8, preferably 1 to 6
(.dbd.C.sub.1-C.sub.6-alkoxycarbonyl), especially 1 to 4 carbon
atoms (.dbd.C.sub.1-C.sub.4-alkoxycarbonyl), in particular 1 to 3
carbon atoms (.dbd.C.sub.1-C.sub.3-alkoxycarbonyl), which is bound
via a carbonyl group (CO) to the remainder of the molecule.
Examples for C.sub.1-C.sub.3-alkoxycarbonyl are methoxycarbonyl,
ethoxycarbonyl, propoxycarbonyl and isopropoxycarbonyl. Examples
for C.sub.1-C.sub.4-alkoxycarbonyl are, apart those mentioned for
C.sub.1-C.sub.3-alkoxycarbonyl, butoxycarbonyl, sec-butoxycarbony,
isobutoxycarbonyl and tert-butoxycarbonyl. Examples for
C.sub.1-C.sub.6-alkoxycarbonyl are, apart those mentioned for
C.sub.1-C.sub.4-alkoxycarbonyl, pentoxycarbonyl and hexoxycarbonyl.
Examples for C.sub.1-C.sub.8-alkoxycarbonyl are, apart those
mentioned for C.sub.1-C.sub.6-alkoxycarbonyl, heptoxycarbonyl,
octoxycarbonyl and 2-ethylhexoxycarbonyl.
[0077] Haloalkoxycarbonyl is an alkoxycarbonyl group wherein a part
or all of the hydrogen atoms are replaced by a halogen atom, in
particular by fluorine and/or chlorine. Preferably,
haloalkoxycarbonyl is fluorinated alkoxycarbonyl. Fluorinated
C.sub.1-C.sub.6-alkoxycarbonyl is a straight-chain or branched
alkoxy group having from 1 to 6 (=fluorinated
C.sub.1-C.sub.6-alkoxycarbonyl), especially 1 to 4 carbon atoms
(=fluorinated C.sub.1-C.sub.4-alkoxycarbonyl), in particular 1 to 3
carbon atoms (=fluorinated C.sub.1-C.sub.3-alkoxycarbonyl), which
is bound via a carbonyl group (CO) to the remainder of the molecule
and wherein at least one of the remaining hydrogen atoms, e.g. 1,
2, 3, or 4 of the hydrogen atoms are replaced by a fluorine atom,
such as in fluoromethoxycarbonyl, difluoromethxycarbonyl,
trifluoromethoxycarbonyl, 1,1-difluoroethoxycarbonyl,
2,2-difluoroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl,
1,1,2,2,2-pentafluoroethpxycarbonyl, 1,1-difluoropropoxycarbonyl,
2,2-difluoropropoxycarbonyl, 3,3,3-trifluoropropoxycarbonyl and the
like.
[0078] C.sub.1-C.sub.6-Alkylthio (also termed as
C.sub.1-C.sub.6-alkylsulfanyl) refers to straight-chain or branched
alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4 carbon atoms
(.dbd.C.sub.1-C.sub.6-alkylthio), which are bound to the remainder
of the molecule via a sulfur atom at any bond in the alkyl group.
Examples for C.sub.1-C.sub.4-alkylthio include methylthio,
ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio,
isobutylthio and tert-butylthio. Examples for
C.sub.1-C.sub.6-alkylthio are, apart those mentioned for
C.sub.1-C.sub.4-alkylthio, 1-, 2- and 3-pentylthio, 1-, 2- and
3-hexylthio and the positional isomers thereof.
[0079] Haloalkylthio is an alkylthio group wherein a part or all of
the hydrogen atoms are replaced by a halogen atom, in particular by
fluorine and/or chlorine. Preferably, haloalkylthio is fluorinated
alkylthio. Fluorinated C.sub.1-C.sub.6 alkylthio (also termed
fluorinated C.sub.1-C.sub.6-alkylsulfanyl) is a straight-chain or
branched alkylthio group having from 1 to 6, in particular 1 to 4
carbon atoms (.dbd.C.sub.1-C.sub.4-alkylthio), wherein at least
one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by
fluorine atoms. Examples include fluoromethylthio,
difluoromethylthio, trifluoromethylthio, 1,1-difluoroethylthio,
2,2-difluoroethylthio, 2,2,2-trifluoroethylthio,
1,1,2,2,2-pentafluoroethylthio, 1,1-difluoropropylthio,
2,2-difluoropropylthio, 3,3-difluoropropylthio,
3,3,3-trifluoropropylthio, 2,2,3,3,3-pentafluoropropylthio and the
like.
[0080] C.sub.1-C.sub.6-Alkylsulfinyl refers to straight-chain or
branched alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4
carbon atoms, which are bound to the remainder of the molecule via
a S(O) group. Examples for C.sub.1-C.sub.4-alkylsulfinyl include
methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl,
n-butylsulfinyl, sec-butylsulfinyl, isobutylsulfinyl and
tertbutylsulfinyl. Examples for C.sub.1-C.sub.6-alkylsulfinyl are,
apart those mentioned for C.sub.1-C.sub.4-alkylsulfinyl, 1-, 2- and
3-pentylsulfinyl, 1-, 2- and 3-hexylsulfinyl and the positional
isomers thereof.
[0081] Haloalkylsulfinyl is an alkylsulfinyl group wherein a part
or all of the hydrogen atoms are replaced by a halogen atom, in
particular by fluorine and/or chlorine. Preferably,
haloalkylsulfinyl is fluorinated alkylsulfinyl. Fluorinated
C.sub.1-C.sub.6 alkylsulfinyl is a straight-chain or branched
alkylsulfinyl group having from 1 to 6, in particular 1 to 4 carbon
atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen
atoms are replaced by fluorine atoms. Examples include
fluoromethylsulfinyl, difluoromethylsulfinyl,
trifluoromethylsulfinyl, 1,1-difluoroethylsulfinyl,
2,2-difluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl,
1,1,2,2,2-pentafluoroethylsulfinyl, 1,1-difluoropropylsulfinyl,
2,2-difluoropropylsulfinyl, 3,3-difluoropropylsulfinyl,
3,3,3-trifluoropropylsulfinyl, 2,2,3,3,3-pentafluoropropylsulfinyl
and the like.
[0082] C.sub.1-C.sub.6-Alkylsulfonyl refers to straight-chain or
branched alkyl groups having 1 to 6 carbon atoms, e.g. 1 to 4
carbon atoms, which are bound to the remainder of the molecule via
a S(O).sub.2 group. Examples for C.sub.1-C.sub.4-alkylsulfonyl
include methylsulfonyl, ethylsulfonyl, propylsulfonyl,
isopropylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl,
isobutylsulfonyl and tert-butylsulfonyl. Examples for
C.sub.1-C.sub.6-alkylsulfonyl are, apart those mentioned for
C.sub.1-C.sub.4-alkylsulfonyl, 1-, 2- and 3-pentylsulfonyl, 1-, 2-
and 3-hexylsulfonyl and the positional isomers thereof.
[0083] Haloalkylsulfonyl is an alkylsulfonyl group wherein a part
or all of the hydrogen atoms are replaced by a halogen atom, in
particular by fluorine and/or chlorine. Preferably,
haloalkylsulfonyl is fluorinated alkylsulfonyl. Fluorinated
C.sub.1-C.sub.6 alkylsulfonyl is a straight-chain or branched
alkylsulfonyl group having from 1 to 6, in particular 1 to 4 carbon
atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen
atoms are replaced by fluorine atoms. Examples include
fluoromethylsulfonyl, difluoromethylsulfonyl,
trifluoromethylsulfonyl, 1,1-difluoroethylsulfonyl,
2,2-difluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl,
1,1,2,2,2-pentafluoroethylsulfonyl, 1,1-difluoropropylsulfonyl,
2,2-difluoropropylsulfonyl, 3,3-difluoropropylsulfonyl,
3,3,3-trifluoropropylsulfonyl, 2,2,3,3,3-pentafluoropropylsulfonyl
and the like.
[0084] C.sub.3-C.sub.6-Cycloalkyl is a cycloaliphatic radical
having from 3 to 6 C atoms, such as cyclopropyl, cyclobutyl,
cyclopentyl and cyclohexyl. C.sub.3-C.sub.8-Cycloalkyl is a
cycloaliphatic radical having from 3 to 8 C atoms. Examples are,
apart those mentioned for C.sub.3-C.sub.6-cycloalkyl, cycloheptyl
and cyclooctyl
[0085] Halocycloalkyl is a cycloalkyl group wherein a part or all
of the hydrogen atoms are replaced by a halogen atom, in particular
by fluorine and/or chlorine. Preferably, halo cycloalkyl is
fluorinated cycloalkyl. Fluorinated C.sub.3-C.sub.6-cycloalkyl is a
cycloaliphatic radical having from 3 to 6 C atoms, such as
cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, wherein at
least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are
replaced by a fluorine atoms such as in 1-fluorocyclopropyl,
2-fluorocyclopropyl, (S)- and (R)-2,2-difluorocyclopropyl,
1,2-difluorocyclopropyl, 2,3-difluorocyclopropyl,
pentafluorocyclopropyl, 1-fluorocyclobutyl, 2-fluorocyclobutyl,
3-fluorocyclobutyl, 2,2-difluorocyclobutyl, 3,3-difluorocyclobutyl,
1,2-difluorocyclobutyl, 1,3-difluorocyclobutyl,
2,3-difluorocyclobutyl, 2,4-difluorocyclobutyl, or
1,2,2-trifluorocyclobutyl.
[0086] C.sub.3-C.sub.6-Cycloalkoxy is C.sub.3-C.sub.6-cycloalkyl as
defined above which is bound via an oxygen atom to the remainder of
the molecule. Examples are cyclopropoxy, cyclobutoxy, cyclopentoxy
and cyclohexoxy.
[0087] C.sub.3-C.sub.8-Cycloalkyl-C.sub.1-C.sub.4-alkyl is
C.sub.1-C.sub.4-alkyl as defined above in which one hydrogen atom
is replaced by a C.sub.3-C.sub.8-cycloalkyl group as defined above.
C.sub.3-C.sub.6-Cycloalkyl-C.sub.1-C.sub.4-alkyl is
C.sub.1-C.sub.4-alkyl as defined above in which one hydrogen atom
is replaced by a C.sub.3-C.sub.6-cycloalkyl group as defined above.
Examples are cyclopropylmethyl, cyclopropyl-1-ethyl,
cyclopropyl-2-ethyl, cyclopentylmethyl, cyclopentyl-1-ethyl,
cyclopentyl-2-ethyl, cyclohexyl methyl, cyclohexyl-1-ethyl,
cyclohexyl-2-ethyl, and the like.
[0088] C.sub.2-C.sub.6-Alkenyl is a singly unsaturated hydrocarbon
radical having 2, 3, 4, 5 or 6 C-atoms, e.g. vinyl, allyl
(2-propen-1-yl), 1-propen-1-yl, methallyl (2-methylprop-2-en-1-yl)
and the like. C.sub.3-C.sub.6-Alkenyl is, in particular, allyl,
1-methylprop-2-en-1-yl, 2-buten-1-yl, 3-buten-1-yl, methallyl,
2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl
or 2-ethylprop-2-en-1-yl.
[0089] Haloalkenyl is an alkenyl group wherein a part or all of the
hydrogen atoms are replaced by a halogen atom, in particular by
fluorine and/or chlorine. Preferably, haloalkenyl is fluorinated
alkenyl. Fluorinated C.sub.2-C.sub.6-alkenyl is a singly
unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 C-atoms, I,
wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms
are replaced by a fluorine atoms such as in 1-fluorovinyl,
2-fluorovinyl, 2,2-fluorovinyl, 3,3,3-fluoropropenyl,
1,1-difluoro-2-propenyl 1-fluoro-2-propenyl and the like.
[0090] C.sub.2-C.sub.6-Alkenyloxy is C.sub.2-C.sub.6-alkenyl as
defined above which is bound via an oxygen atom to the remainder of
the molecule. Examples are vinyloxy, allyloxy (2-propen-1-yloxy),
1-propen-1-yloxy, methallyloxy (2-methylprop-2-en-1-yloxy) and the
like. C.sub.3-C.sub.6-Alkenyloxy is, in particular, allyloxy,
1-methylprop-2-en-1-yloxy, 2-buten-1-yloxy, 3-buten-1-yloxy,
methallyloxy, 2-penten-1-yloxy, 3-penten-1-yloxy, 4-penten-1-yloxy,
1-methyl but-2-en-1-yloxy or 2-ethylprop-2-en-1-yloxy.
[0091] C.sub.2-C.sub.6-Alkenylthio is C.sub.2-C.sub.6-alkenyl as
defined above which is bound via a sulfur atom to the remainder of
the molecule. Examples are vinylthio, allylthio
(2-propen-1-ylthio), 1-propen-1-ylthio, methallylthio
(2-methylprop-2-en-1-ylthio) and the like. C.sub.3-C.sub.6-Alkenyl
is, in particular, allylthio, 1-methylprop-2-en-1-ylthio,
2-buten-1-ylthio, 3-buten-1-ylthio, methallylthio,
2-penten-1-ylthio, 3-penten-1-ylthio, 4-penten-1-ylthio,
1-methylbut-2-en-1-ylthio or 2-ethylprop-2-en-1-ylthio.
[0092] C.sub.2-C.sub.6-Alkenylsulfinyl is C.sub.2-C.sub.6-alkenyl
as defined above which is bound via an S(O) group to the remainder
of the molecule. Examples are vinylsulfinyl, allylsulfinyl
(2-propen-1-ylsulfinyl), 1-propen-1-ylsulfinyl, methallylsulfinyl
(2-methylprop-2-en-1-ylsulfinyl) and the like.
C.sub.3-C.sub.6-Alkenyl is, in particular, allylsulfinyl,
1-methylprop-2-en-1-ylsulfinyl, 2-buten-1-ylsulfinyl,
3-buten-1-ylsulfinyl, methallylsulfinyl, 2-penten-1-ylsulfinyl,
3-penten-1-ylsulfinyl, 4-penten-1-ylsulfinyl,
1-methylbut-2-en-1-ylsulfinyl or 2-ethylprop-2-en-1-ylsulfinyl.
[0093] C.sub.2-C.sub.6-Alkenylsulfonyl is C.sub.2-C.sub.6-alkenyl
as defined above which is bound via an S(O).sub.2, group to the
remainder of the molecule. Examples are vinylsulfonyl,
allylsulfonyl (2-propen-1-ylsulfonyl), 1-propen-1-ylsulfonyl,
methallylsulfonyl (2-methylprop-2-en-1-ylsulfonyl) and the like.
C.sub.3-C.sub.6-Alkenyl is, in particular, allylsulfonyl,
1-methylprop-2-en-1-ylsulfonyl, 2-buten-1-ylsulfonyl,
3-buten-1-ylsulfonyl, methallylsulfonyl, 2-penten-1-ylsulfonyl,
3-penten-1-ylsulfonyl, 4-penten-1-ylsulfonyl,
1-methylbut-2-en-1-ylsulfonyl or 2-ethylprop-2-en-1-ylsulfonyl.
[0094] C.sub.2-C.sub.6-Alkenylcarbonyl is C.sub.2-C.sub.6-alkenyl
as defined above which is bound via a CO group to the remainder of
the molecule. Examples are vinylcarbonyl, allylcarbonyl
(2-propen-1-ylcarbonyl), 1-propen-1-ylcarbonyl, methallylcarbonyl
(2-methylprop-2-en-1-ylcarbonyl) and the like.
C.sub.3-C.sub.6-Alkenyl is, in particular, allylcarbonyl,
1-methylprop-2-en-1-ylcarbonyl, 2-buten-1-ylcarbonyl,
3-buten-1-ylcarbonyl, methallylcarbonyl, 2-penten-1-ylcarbonyl,
3-penten-1-ylcarbonyl, 4-penten-1-ylcarbonyl,
1-methylbut-2-en-1-ylcarbonyl or 2-ethylprop-2-en-1-ylcarbonyl.
[0095] C.sub.2-C.sub.6-Alkenylcarbonyloxy is
C.sub.2-C.sub.6-alkenyl as defined above which is bound via a
C(O)--O group to the remainder of the molecule. Examples are
vinylcarbonyloxy, allylcarbonyloxy (2-propen-1-ylcarbonyloxy),
1-propen-1-ylcarbonyloxy, methallylcarbonyl
(2-methylprop-2-en-1-ylcarbonyloxy) and the like.
C.sub.3-C.sub.6-Alkenylcarbonyloxy is, in particular,
allylcarbonyloxy, 1-methylprop-2-en-1-ylcarbonyloxy,
2-buten-1-ylcarbonyloxy, 3-buten-1-ylcarbonyloxy,
methallylcarbonyloxy, 2-penten-1-ylcarbonyloxy,
3-penten-1-ylcarbonyloxy, 4-penten-1-ylcarbonyloxy,
1-methylbut-2-en-1-ylcarbonyloxy or
2-ethylprop-2-en-1-ylcarbonyloxy.
[0096] C.sub.2-C.sub.6-Alkenyloxycarbonyl is
C.sub.2-C.sub.6-alkenyl as defined above which is bound via a
O--C(O) group to the remainder of the molecule. Examples are
vinyloxycarbonyl, allyloxycarbonyl (2-propen-1-yloxycarbonyl),
1-propen-1-yloxycarbonyl, methallyloxycarbonyl
(2-methylprop-2-en-1-yloxycarbonyl) and the like.
C.sub.3-C.sub.6-Alkenyl is, in particular, allyloxycarbonyl,
1-methylprop-2-en-1-yloxycarbonyl, 2-buten-1-yloxycarbonyl,
3-buten-1-yloxycarbonyl, methallyloxycarbonyl,
2-penten-1-yloxycarbonyl, 3-penten-1-yloxycarbonyl,
4-penten-1-yloxycarbonyl, 1-methylbut-2-en-1-yloxycarbonyl or
2-ethylprop-2-en-1-yloxycarbonyl.
[0097] C.sub.2-C.sub.6-Alkynyl is a straight-chain or branched
hydrocarbon group having 2 to 6 carbon atoms and one or two triple
bonds in any position, such as ethynyl, 1-propynyl, 2-propynyl,
1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl,
2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl,
1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl,
1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl,
3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl,
1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl,
2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl,
4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl,
1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl,
2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl,
1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl
and the like.
[0098] Haloalkynyl is an alkynyl group wherein a part or all of the
hydrogen atoms are replaced by a halogen atom, in particular by
fluorine and/or chlorine. Preferably, haloalkynyl is fluorinated
alkynyl. Fluorinated C.sub.2-C.sub.6-alkynyl is a singly
unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 C-atoms, I,
wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms
are replaced by a fluorine atoms.
[0099] C.sub.2-C.sub.6-Alkynyloxy is C.sub.2-C.sub.6-alkynyl as
defined above which is bound via an oxygen atom to the remainder of
the molecule. Examples are ethynyloxy, 1-propynyloxy,
2-propynyloxy, 1-butynyloxy, 2-butynyloxy, 3-butynyloxy,
1-methyl-2-propynyloxy, 1-pentynyloxy, 2-pentynyloxy,
3-pentynyloxy, 4-pentynyloxy, 1-methyl-2-butynyloxy,
1-methyl-3-butynyloxy, 2-methyl-3-butynyloxy,
3-methyl-1-butynyloxy, 1,1-dimethyl-2-propynyloxy,
1-ethyl-2-propynyloxy, 1-hexynyloxy, 2-hexynyloxy, 3-hexynyloxy,
4-hexynyloxy, 5-hexynyloxy, 1-methyl-2-pentynyloxy,
1-methyl-3-pentynyloxy, 1-methyl-4-pentynyloxy,
2-methyl-3-pentynyloxy, 2-methyl-4-pentynyloxy,
3-methyl-1-pentynyloxy, 3-methyl-4-pentynyloxy,
4-methyl-1-pentynyloxy, 4-methyl-2-pentynyloxy,
1,1-dimethyl-2-butynyloxy, 1,1-dimethyl-3-butynyloxy,
1,2-dimethyl-3-butynyloxy, 2,2-dimethyl-3-butynyloxy,
3,3-dimethyl-1-butynyloxy, 1-ethyl-2-butynyloxy,
1-ethyl-3-butynyloxy, 2-ethyl-3-butynyloxy,
1-ethyl-1-methyl-2-propynyloxy and the like.
[0100] C.sub.2-C.sub.6-Alkynylthio is C.sub.2-C.sub.6-alkynyl as
defined above which is bound via a sulfur atom to the remainder of
the molecule. Examples are ethynylthio, 1-propynylthio,
2-propynylthio, 1-butynylthio, 2-butynylthio, 3-butynylthio,
1-methyl-2-propynylthio, 1-pentynylthio, 2-pentynylthio,
3-pentynylthio, 4-pentynylthio, 1-methyl-2-butynylthio,
1-methyl-3-butynylthio, 2-methyl-3-butynylthio,
3-methyl-1-butynylthio, 1,1-dimethyl-2-propynylthio,
1-ethyl-2-propynylthio, 1-hexynylthio, 2-hexynylthio,
3-hexynylthio, 4-hexynylthio, 5-hexynylthio,
1-methyl-2-pentynylthio, 1-methyl-3-pentynylthio,
1-methyl-4-pentynylthio, 2-methyl-3-pentynylthio,
2-methyl-4-pentynylthio, 3-methyl-1-pentynylthio,
3-methyl-4-pentynylthio, 4-methyl-1-pentynylthio,
4-methyl-2-pentynylthio, 1,1-dimethyl-2-butynylthio,
1,1-dimethyl-3-butynylthio, 1,2-dimethyl-3-butynylthio,
2,2-dimethyl-3-butynylthio, 3,3-dimethyl-1-butynylthio,
1-ethyl-2-butynylthio, 1-ethyl-3-butynylthio,
2-ethyl-3-butynylthio, 1-ethyl-1-methyl-2-propynylthio and the
like.
[0101] C.sub.2-C.sub.6-Alkynylsulfinyl is C.sub.2-C.sub.6-alkynyl
as defined above which is bound via an S(O) group to the remainder
of the molecule. Examples are ethynylsulfinyl, 1-propynylsulfinyl,
2-propynylsulfinyl, 1-butynylsulfinyl, 2-butynylsulfinyl,
3-butynylsulfinyl, 1-methyl-2-propynylsulfinyl, 1-pentynylsulfinyl,
2-pentynylsulfinyl, 3-pentynylsulfinyl, 4-pentynylsulfinyl,
1-methyl-2-butynylsulfinyl, 1-methyl-3-butynylsulfinyl,
2-methyl-3-butynylsulfinyl, 3-methyl-1-butynylsulfinyl,
1,1-dimethyl-2-propynylsulfinyl, 1-ethyl-2-propynylsulfinyl,
1-hexynylsulfinyl, 2-hexynylsulfinyl, 3-hexynylsulfinyl,
4-hexynylsulfinyl, 5-hexynylsulfinyl, 1-methyl-2-pentynylsulfinyl,
1-methyl-3-pentynylsulfinyl, 1-methyl-4-pentynylsulfinyl,
2-methyl-3-pentynylsulfinyl, 2-methyl-4-pentynylsulfinyl,
3-methyl-1-pentynylsulfinyl, 3-methyl-4-pentynylsulfinyl,
4-methyl-1-pentynylsulfinyl, 4-methyl-2-pentynylsulfinyl,
1,1-dimethyl-2-butynylsulfinyl, 1,1-dimethyl-3-butynylsulfinyl,
1,2-dimethyl-3-butynylsulfinyl, 2,2-dimethyl-3-butynylsulfinyl,
3,3-dimethyl-1-butynylsulfinyl, 1-ethyl-2-butynylsulfinyl,
1-ethyl-3-butynylsulfinyl, 2-ethyl-3-butynylsulfinyl,
1-ethyl-1-methyl-2-propynylsulfinyl and the like.
[0102] C.sub.2-C.sub.6-Alkynylsulfonyl is C.sub.2-C.sub.6-alkynyl
as defined above which is bound via an S(O).sub.2, group to the
remainder of the molecule. Examples are ethynylsulfonyl,
1-propynylsulfonyl, 2-propynylsulfonyl, 1-butynylsulfonyl,
2-butynylsulfonyl, 3-butynylsulfonyl, 1-methyl-2-propynylsulfonyl,
1-pentynylsulfonyl, 2-pentynylsulfonyl, 3-pentynylsulfonyl,
4-pentynylsulfonyl, 1-methyl-2-butynylsulfonyl,
1-methyl-3-butynylsulfonyl, 2-methyl-3-butynylsulfonyl,
3-methyl-1-butynylsulfonyl, 1,1-dimethyl-2-propynylsulfonyl,
1-ethyl-2-propynylsulfonyl, 1-hexynylsulfonyl, 2-hexynylsulfonyl,
3-hexynylsulfonyl, 4-hexynylsulfonyl, 5-hexynylsulfonyl,
1-methyl-2-pentynylsulfonyl, 1-methyl-3-pentynylsulfonyl,
1-methyl-4-pentynylsulfonyl, 2-methyl-3-pentynylsulfonyl,
2-methyl-4-pentynylsulfonyl, 3-methyl-1-pentynylsulfonyl,
3-methyl-4-pentynylsulfonyl, 4-methyl-1-pentynylsulfonyl,
4-methyl-2-pentynylsulfonyl, 1,1-dimethyl-2-butynylsulfonyl,
1,1-dimethyl-3-butynylsulfonyl, 1,2-dimethyl-3-butynylsulfonyl,
2,2-dimethyl-3-butynylsulfonyl, 3,3-dimethyl-1-butynylsulfonyl,
1-ethyl-2-butynylsulfonyl, 1-ethyl-3-butynylsulfonyl,
2-ethyl-3-butynylsulfonyl, 1-ethyl-1-methyl-2-propynylsulfonyl and
the like.
[0103] C.sub.2-C.sub.6-Alkynylcarbonyl is C.sub.2-C.sub.6-alkynyl
as defined above which is bound via a CO group to the remainder of
the molecule. Examples are ethynylcarbonyl, 1-propynylcarbonyl,
2-propynylcarbonyl, 1-butynylcarbonyl, 2-butynylcarbonyl,
3-butynylcarbonyl, 1-methyl-2-propynylcarbonyl, 1-pentynylcarbonyl,
2-pentynylcarbonyl, 3-pentynylcarbonyl, 4-pentynylcarbonyl,
1-methyl-2-butynylcarbonyl, 1-methyl-3-butynylcarbonyl,
2-methyl-3-butynylcarbonyl, 3-methyl-1-butynylcarbonyl,
1,1-dimethyl-2-propynylcarbonyl, 1-ethyl-2-propynylcarbonyl,
1-hexynylcarbonyl, 2-hexynylcarbonyl, 3-hexynylcarbonyl,
4-hexynylcarbonyl, 5-hexynylcarbonyl, 1-methyl-2-pentynylcarbonyl,
1-methyl-3-pentynylcarbonyl, 1-methyl-4-pentynylcarbonyl,
2-methyl-3-pentynylcarbonyl, 2-methyl-4-pentynylcarbonyl,
3-methyl-1-pentynylcarbonyl, 3-methyl-4-pentynylcarbonyl,
4-methyl-1-pentynylcarbonyl, 4-methyl-2-pentynylcarbonyl,
1,1-dimethyl-2-butynylcarbonyl, 1,1-dimethyl-3-butynylcarbonyl,
1,2-dimethyl-3-butynylcarbonyl, 2,2-dimethyl-3-butynylcarbonyl,
3,3-dimethyl-1-butynylcarbonyl, 1-ethyl-2-butynylcarbonyl,
1-ethyl-3-butynylcarbonyl, 2-ethyl-3-butynylcarbonyl,
1-ethyl-1-methyl-2-propynylcarbonyl and the like.
[0104] C.sub.2-C.sub.6-Alkynylcarbonyloxy is
C.sub.2-C.sub.6-alkynyl as defined above which is bound via a
C(O)--O group to the remainder of the molecule. Examples are
ethynylcarbonyloxy, 1-propynylcarbonyloxy, 2-propynylcarbonyloxy,
1-butynylcarbonyloxy, 2-butynylcarbonyloxy, 3-butynylcarbonyloxy,
1-methyl-2-propynylcarbonyloxy, 1-pentynylcarbonyloxy,
2-pentynylcarbonyloxy, 3-pentynylcarbonyloxy,
4-pentynylcarbonyloxy, 1-methyl-2-butynylcarbonyloxy,
1-methyl-3-butynylcarbonyloxy, 2-methyl-3-butynylcarbonyloxy,
3-methyl-1-butynylcarbonyloxy, 1,1-dimethyl-2-propynylcarbonyloxy,
1-ethyl-2-propynylcarbonyloxy, 1-hexynylcarbonyloxy,
2-hexynylcarbonyloxy, 3-hexynylcarbonyloxy, 4-hexynylcarbonyloxy,
5-hexynylcarbonyloxy, 1-methyl-2-pentynylcarbonyloxy,
1-methyl-3-pentynylcarbonyloxy, 1-methyl-4-pentynylcarbonyloxy,
2-methyl-3-pentynylcarbonyloxy, 2-methyl-4-pentynylcarbonyloxy,
3-methyl-1-pentynylcarbonyloxy, 3-methyl-4-pentynylcarbonyloxy,
4-methyl-1-pentynylcarbonyloxy, 4-methyl-2-pentynylcarbonyloxy,
1,1-dimethyl-2-butynylcarbonyloxy,
1,1-dimethyl-3-butynylcarbonyloxy,
1,2-dimethyl-3-butynylcarbonyloxy,
2,2-dimethyl-3-butynylcarbonyloxy,
3,3-dimethyl-1-butynylcarbonyloxy, 1-ethyl-2-butynylcarbonyloxy,
1-ethyl-3-butynylcarbonyloxy, 2-ethyl-3-butynylcarbonyloxy,
1-ethyl-1-methyl-2-propynylcarbonyloxy and the like.
[0105] C.sub.2-C.sub.6-Alkynyloxycarbonyl is
C.sub.2-C.sub.6-alkynyl as defined above which is bound via a
O--C(O) group to the remainder of the molecule. Examples are
ethynyloxycarbonyl, 1-propynyloxycarbonyl, 2-propynyloxycarbonyl,
1-butynyloxycarbonyl, 2-butynyloxycarbonyl, 3-butynyloxycarbonyl,
1-methyl-2-propynyloxycarbonyl, 1-pentynyloxycarbonyl,
2-pentynyloxycarbonyl, 3-pentynyloxycarbonyl,
4-pentynyloxycarbonyl, 1-methyl-2-butynyloxycarbonyl,
1-methyl-3-butynyloxycarbonyl, 2-methyl-3-butynyloxycarbonyl,
3-methyl-1-butynyloxycarbonyl, 1,1-dimethyl-2-propynyloxycarbonyl,
1-ethyl-2-propynyloxycarbonyl, 1-hexynyloxycarbonyl,
2-hexynyloxycarbonyl, 3-hexynyloxycarbonyl, 4-hexynyloxycarbonyl,
5-hexynyloxycarbonyl, 1-methyl-2-pentynyloxycarbonyl,
1-methyl-3-pentynyloxycarbonyl, 1-methyl-4-pentynyloxycarbonyl,
2-methyl-3-pentynyloxycarbonyl, 2-methyl-4-pentynyloxycarbonyl,
3-methyl-1-pentynyloxycarbonyl, 3-methyl-4-pentynyloxycarbonyl,
4-methyl-1-pentynyloxycarbonyl, 4-methyl-2-pentynyloxycarbonyl,
1,1-dimethyl-2-butynyloxycarbonyl,
1,1-dimethyl-3-butynyloxycarbonyl,
1,2-dimethyl-3-butynyloxycarbonyl,
2,2-dimethyl-3-butynyloxycarbonyl,
3,3-dimethyl-1-butynyloxycarbonyl, 1-ethyl-2-butynyloxycarbonyl,
1-ethyl-3-butynyloxycarbonyl, 2-ethyl-3-butynyloxycarbonyl,
1-ethyl-1-methyl-2-propynyloxycarbonyl and the like.
[0106] C.sub.1-C.sub.6-Alkylene is a linear or bridged hydrocarbon
bridging group having 1, 2, 3, 4, 5 or 6 carbon atoms. Examples for
C.sub.1-C.sub.2-alkylene are methylene, 1,1-ethylene and
1,2-ethylene. Examples for C.sub.1-C.sub.3-alkylene are, apart
those mentioned for C.sub.1-C.sub.2-alkylene, 1,1-propylene,
2,2-propylene, 1,2-propylene, 2,3-propylene and 1,3-propylene.
Examples for C.sub.1-C.sub.4-alkylene are, apart those mentioned
for C.sub.1-C.sub.3-alkylene, 1,1-butylene, 2,2-butylene,
1,2-butylene, 1,3-butylene, 1,4-butylene, 2-methyl-1,2-propylene,
2-methyl-2,3-propylene and the like. Examples for
C.sub.1-C.sub.6-alkylene are, apart those mentioned for
C.sub.1-C.sub.4-alkylene, 1,1-pentylene, 2,2-pentylene,
3,3-pentylene, 1,2-pentylene, 2,3-pentylene, 3,4-pentylene,
2,4-pentylene, 2,2-dimethyl-1,3-propylene, 1,5-pentylene,
1,6-hexylene and the like.
[0107] Aryl is a carbocyclic aromatic radical having 6 to 14 carbon
atoms, such as phenyl, naphthyl, anthracenyl or phenanthrenyl.
C.sub.6-C.sub.10-Aryl is phenyl or naphthyl.
[0108] Aryloxy is carbocyclic aromatic radical having 6 to 14
carbon atoms which is attached via oxygen, such as phenoxy,
naphthyloxy, anthracenyloxy or phenanthrenyloxy.
C.sub.6-C.sub.10-Aryloxy is phenoxy or naphthoxy.
[0109] Arylthio is a carbocyclic aromatic radical having 6 to 14
carbon atoms which is attached via sulfur, such as phenylthio,
naphthylthio, anthracenylthio or phenanthrenylthio.
C.sub.6-C.sub.10-Arylthio is phenylthio or naphthylthio.
[0110] Arylsulfinyl is a carbocyclic aromatic radical having 6 to
14 carbon atoms which is attached via an SO group, such as
phenylsulfinyl, naphthylsulfinyl, anthracenylsulfinyl or
phenanthrenylsulfinyl. C.sub.6-C.sub.10-Arylsulfinyl is
phenylsulfinyl or naphthylsulfinyl.
[0111] Arylsulfonyl is a carbocyclic aromatic radical having 6 to
14 carbon atoms which is attached via an S(O).sub.2 group, such as
phenylsulfonyl, naphthylsulfonyl, anthracenylsulfonyl or
phenanthrenylsulfonyl. C.sub.6-C.sub.10-Arylsulfonyl is
phenylsulfonyl or naphthylsulfonyl.
[0112] Arylcarbonyl is a carbocyclic aromatic radical having 6 to
14 carbon atoms which is attached via a CO group, such as
phenylcarbonyl, naphthylcarbonyl, anthracenylcarbony) or
phenanthrenylcarbonyl. C.sub.6-C.sub.10-Arylcarbonyl is
phenylcarbonyl or naphthylcarbonyl.
[0113] Arylcarbonyloxy is a carbocyclic aromatic radical having 6
to 14 carbon atoms which is attached via a CO--O-- group, such as
phenylcarbonyloxy, naphthylcarbonyloxy, anthracenylcarbonyloxy or
phenanthrenylcarbonyloxy. C.sub.6-C.sub.10-Arylcarbonyloxy is
phenylcarbonyloxy or naphthylcarbonyloxy.
[0114] Aryloxycarbonyl is a carbocyclic aromatic radical having 6
to 14 carbon atoms which is attached via a O--CO group, such as
phenoxycarbonyl, naphthyloxycarbonyl, anthracenyloxycarbonyl or
phenanthrenyloxycarbonyl. C.sub.6-C.sub.10-Aryloxycarbonyl is
phenoxycarbonyl or naphthyloxycarbonyl.
[0115] Arylalkyl is an alkyl radical (as defined above), for
example C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.6-alkyl or in
particular C.sub.1-C.sub.4-alkyl, where a hydrogen atom is replaced
by an aryl group, such as benzyl, phenethyl and the like.
[0116] Arylalkoxy is an alkoxy radical (as defined above), for
example C.sub.1-C.sub.8-alkoxy, C.sub.1-C.sub.6-alkoxy or in
particular C.sub.1-C.sub.4-alkoxy, where one hydrogen atom is
replaced by an aryl group, such as benzyloxy, phenethyloxy and the
like.
[0117] Aryloxyalkyl is an alkyl radical (as defined above), for
example C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.6-alkyl or in
particular C.sub.1-C.sub.4-alkyl, where a hydrogen atom is replaced
by an aryloxy group as defined above, such as phenoxymethyl,
naphthoxymethyl, 2-phenoxyethyl, 2-naphthoxyethyl and the like.
[0118] Arylalkylthio is an alkylthio radical (as defined above),
for example C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.6-alkylthio or
in particular C.sub.1-C.sub.4-alkylthio, where a hydrogen atom is
replaced by an aryl group as defined above, such as benzylthio,
naphthylmethyltho, phenethylthio, 2-naphthylethylthio and the
like.
[0119] Arylthioalkyl is an alkyl radical (as defined above), for
example C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.6-alkyl or in
particular C.sub.1-C.sub.4-alkyl, where a hydrogen atom is replaced
by an arylthio group as defined above, such as phenylthiomethyl,
naphthylthiomethyl, 2-phenylthioethyl, 2-naphthylthioethyl and the
like.
[0120] Arylalkylcarbonyl is an arylalkyl radical (as defined
above), for example aryl-C.sub.1-C.sub.8-alkyl,
aryl-C.sub.1-C.sub.6-alkyl or in particular
aryl-C.sub.1-C.sub.4-alkyl, which is bound via a CO group, such as
benzoyl, phenethylcarbonyl and the like.
[0121] Arylalkoxycarbonyl is an arylalkoxy radical (as defined
above), for example aryl-C.sub.1-C.sub.8-alkoxy,
aryl-C.sub.1-C.sub.6-alkoxy or in particular
aryl-C.sub.1-C.sub.4-alkoxy, which is bound via a CO group, such as
benzoxycarbonyl, 2-phenylethoxycarbonyl and the like.
[0122] Arylalkylcarbonyloxy is an arylalkyl radical (as defined
above), for example aryl-C.sub.1-C.sub.8-alkyl,
aryl-C.sub.1-C.sub.6-alkyl or in particular
aryl-C.sub.1-C.sub.4-alkyl, which is bound via a CO--Ogroup, such
as benzoyloxy, phenethylcarbonyloxy and the like.
[0123] Aryl-C.sub.2-C.sub.4-alkenyl is a C.sub.2-C.sub.4-alkenyl
radical (as defined above), where a hydrogen atom is replaced by an
aryl group, such as 2-phenylethenyl, 3-phenyl-prop-2-enyl,
3-phenyl-prop-1-enyl and the like.
[0124] Aryl-C.sub.2-C.sub.4-alkynyl is a C.sub.2-C.sub.4-alkynyl
radical (as defined above), where a hydrogen atom is replaced by an
aryl group, such as 2-phenylethynyl, 3-phenyl-prop-2-ynyl,
3-phenyl-prop-1-ynyl and the like.
[0125] 5- or 6-membered saturated, partly unsaturated or aromatic
heterocyclic rings containing 1, 2, 3 or 4 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups are either 5-
or 6-membered saturated heterocyclic rings containing 1, 2, 3 or 4
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups as ring members, i.e. rings without any (C--C/C--N/N--N)
double bonds in the ring scaffold (C--C/C--N/N--N), or 5- or
6-membered partly unsaturated heterocyclic rings containing 1, 2, 3
or 4 heteroatoms selected from O, S and N and optionally 1 or 2
carbonyl groups as ring members, i.e. a 5-membered ring with one
(C--C/C--N/N--N) double bond or a 6-membered ring with one or two
(C--C/C--N/N--N) double bonds in the ring scaffold, or are 5- or
6-membered aromatic heterocyclic rings containing 1, 2, 3 or 4
heteroatoms selected from O, S and N as ring members, i.e. rings
with aromatic unsaturation. In the heterocyclic rings, the N atoms
can be present as such (then, they are part of a ring double bond)
or as NR groups where R is H or an appropriate substituent such as
alkyl, alkoxy, formyl, alkylcarbonyl arylcarbonyl
arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl or
arylalkylsulfonyl. The rings can be bound via a carbon atom or via
a nitrogen atom to the remainder of the molecule. In 5-membered
heteroaromatic rings containing 1 heteroatom, this is selected from
O, S and N. In 5-membered heteroaromatic rings containing 2
heteroatoms, one is selected from O, S and N and the second
heteroatom is N. In 5-membered heteroaromatic rings containing 3
heteroatoms, one is selected from O, S and N and the other two
heteroatoms are N. In 5-membered heteroaromatic rings containing 4
heteroatoms, all four heteroatoms are N. In 6-membered
heteroaromatic rings, all heteroatoms are N (1, 2 or 3 nitrogen
atoms).
[0126] Examples of 5- or 6-membered saturated heterocyclic rings
containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups are pyrrolidinyl, e.g. 1-, 2- or
3-pyrrolidinyl, pyrrolidinonyl, e.g. pyrrolidin-2-on-1-yl,
pyrrolidin-2-on-3-yl, pyrrolidin-2-on-4-yl, pyrrolidin-2-on-5-yl,
pyrrolidin-3-on-1-yl, pyrrolidin-3-on-2-yl, pyrrolidin-3-on-4-yl or
pyrrolidin-3-on-5-yl, pyrrolidindionyl, e.g.
pyrrolidin-2,5-dion-1-yl or pyrrolidin-2,5-dion-3-yl,
tetrahyrofuranyl, e.g. tetrahyrofuran-2-yl or tetrahyrofuran-3-yl,
tetrahydrothienyl, e.g. tetrahydrothien-2-yl or
tetrahydrothien-3-yl, pyrazolidinyl, e.g. pyrazolidin-1-yl,
pyrazolidin-3-yl or pyrazolidin-4-yl, imidazolidinyl, e.g.
imidazolidin-1-yl, imidazolidin-2-yl or imidazolidin-4-yl,
imidazolidinonyl, e.g. imidazolidin-2-on-1-yl or
imidazolidin-2-on-4-yl, dioxolanyl, e.g. 1,3-dioxolan-2-yl or
1,3-dioxolan-4-yl, oxazolidinyl, e.g. oxazolidin-2-yl,
oxazolidin-3-yl, oxazolidin-4-yl or oxazolidin-5-yl,
oxazolidinonyl, e.g. oxazolidin-2-on-3-yl, oxazolidin-2-on-4-yl or
oxazolidin-2-on-5-yl, isoxazolidinyl, e.g. isoxazolidin-2-yl,
isoxazolidin-3-yl, isoxazolidin-4-yl or isoxazolidin-5-yl,
isoxazolidinonyl, e.g. isoxazolidin-3-on-2-yl,
isoxazolidin-3-on-4-yl or isoxazolidin-3-on-5-yl,
1,3-dithiolan-2-yl or 1,3-dithiolan-4-yl, thiazolidinyl, e.g.
thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl or
thiazolidin-5-yl, thiazolidinonyl, e.g. thiazolidin-2-on-3-yl,
thiazolidin-2-on-4-yl or thiazolidin-2-on-5-yl, isothiazolidinyl,
e.g. isothiazolidin-2-yl, isothiazolidin-3-yl, isothiazolidin-4-yl
or isothiazolidin-5-yl, isothiazolidinonyl, e.g.
isothiazolidin-3-on-2-yl, isothiazolidin-3-on-4-yl or
isothiazolidin-3-on-5-yl, triazolidinyl, e.g.
[1,2,3]triazolidin-1-yl, [1,2,3]triazolidin-2-yl,
[1,2,3]triazolidin-4-yl, [1,2,4]triazolidin-1-yl,
[1,2,4]triazolidin-2-yl, [1,2,4]triazolidin-3-yl or
[1,2,4]triazolidin-4-yl, oxadiazolidinyl, e.g.
[1,2,3]oxadiazolidin-2-yl, [1,2,3]oxadiazolidin-3-yl,
[1,2,3]oxadiazolidin-4-yl, [1,2,3]oxadiazolidin-5-yl,
[1,2,5]oxadiazolidin-2-yl, [1,2,5]oxadiazolidin-3-yl,
[1,2,4]oxadiazolidin-2-yl, [1,2,4]oxadiazolidin-3-yl,
[1,2,4]oxadiazolidin-4-yl, [1,2,4]oxadiazolidin-5-yl,
[1,3,4]oxadiazolidin-2-yl or [1,3,4]oxadiazolidin-3-yl,
thiadiazolidinyl, e.g. [1,2,3]thiadiazolidin-2-yl,
[1,2,3]thiadiazolidin-3-yl, [1,2,3]thiadiazolidin-4-yl,
[1,2,3]thiadiazolidin-5-yl, [1,2,5]thiadiazolidin-2-yl,
[1,2,5]thiadiazolidin-3-yl, [1,2,4]thiadiazolidin-2-yl,
[1,2,4]thiadiazolidin-3-yl, [1,2,4]thiadiazolidin-4-yl,
[1,2,4]thiadiazolidin-5-yl, [1,3,4]thiadiazolidin-2-yl or
[1,3,4]thiadiazolidin-3-yl, tetrazolidinyl, e.g.
[1,2,3,4]tetrazolidin-1-yl, [1,2,3,4]tetrazolidin-2-yl or
[1,2,3,4]tetrazolidin-5-yl, piperidinyl, e.g. piperidin-1-yl,
piperidin-2-yl, piperidin-3-yl or piperidin-4-yl, piperidinonyl,
e.g. piperidin-2-on-1-yl, piperidin-2-on-3-yl, piperidin-2-on-4-yl,
piperidin-2-on-5-yl, piperidin-2-on-6-yl, piperidin-3-on-1-yl,
piperidin-3-on-2-yl, piperidin-3-on-4-yl, piperidin-3-on-5-yl,
piperidin-3-on-6-yl, piperidin-4-on-1-yl, piperidin-4-on-2-yl or
piperidin-4-on-3-yl, piperidindionyl, e.g. piperidin-2,6-dion-1-yl,
piperidin-2,6-dion-3-yl or piperidin-2,6-dion-4-yl,
tetrahydropyranyl, e.g. tetrahydropyran-2-yl or
tetrahydropyran-3-yl, tetrahydropyranonyl, e.g.
tetrahydropyran-2-on-3-yl, tetrahydropyran-2-on-4-yl,
tetrahydropyran-2-on-5-yl or tetrahydropyran-2-on-6-yl,
tetrahydrothiopyranyl, e.g. tetrahydrothiopyran-2-yl or
tetrahydrothiopyran-3-yl, piperazinyl, e.g. piperazin-1-yl or
piperazin-2-yl, dioxanyl, e.g. 1,3-dioxan-2-yl, 1,3-dioxan-4-yl,
1,3-dioxan-5-yl or 1,4-dioxan-2-yl, morpholinyl, e.g.
morpholin-2-yl, morpholin-3-yl or morpholin-4-yl, thiomorpholinyl,
e.g. thiomorpholin-2-yl, thiomorpholin-3-yl or thiomorpholin-4-yl
and the like.
[0127] Examples of 5- or 6-membered partly unsaturated heterocyclic
rings containing 1, 2, 3 or 4 heteroatoms selected from O, S and N
and optionally 1 or 2 carbonyl groups are pyrrolinyl, e.g.
2,3-dihydropyrrol-1-yl, 2,3-dihydropyrrol-2-yl,
2,3-dihydropyrrol-3-yl, 2,3-dihydropyrrol-4-yl,
2,3-dihydropyrrol-5-yl, 2,5-dihydropyrrol-1-yl,
2,5-dihydropyrrol-2-yl or 2,5-dihydropyrrol-3-yl, pyrrolinonyl,
e.g. 2,3-dihydropyrrol-2-on-1-yl, 2,3-dihydropyrrol-2-on-3-yl,
2,3-dihydropyrrol-2-on-4-yl or 2,3-dihydropyrrol-2-on-5-yl,
dihydrofuranyl, e.g. 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl,
2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 3,4-dihydrofuran-2-yl
or 3,4-dihydrofuran-4-yl, dihydrothienyl, e.g.
2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl,
2,3-dihydrothien-4-yl, 2,3-dihydrothien-5-yl, 3,4-dihydrothien-2-yl
or 3,4-dihydrothien-4-yl, pyrazolinyl, e.g.
2,3-dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl,
2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl,
2,3-dihydropyrazol-5-yl, 2,5-dihydropyrazol-1-yl,
2,5-dihydropyrazol-2-yl, 2,5-dihydropyrazol-3-yl,
2,5-dihydropyrazol-4-yl, 2,5-dihydropyrazol-5-yl,
4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-2-yl,
4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl or
4,5-dihydropyrazol-5-yl, imidazolinyl, e.g.
2,3-dihydroimidazol-1-yl, 2,3-dihydroimidazol-2-yl,
2,3-dihydroimidazol-3-yl, 2,3-dihydroimidazol-4-yl,
2,3-dihydroimidazol-5-yl, 2,5-dihydroimidazol-1-yl,
2,5-dihydroimidazol-2-yl, 2,5-dihydroimidazol-4-yl,
2,5-dihydroimidazol-5-yl, 4,5-dihydroimidazol-1-yl,
4,5-dihydroimidazol-2-yl, 4,5-dihydroimidazol-4-yl or
4,5-dihydroimidazol-5-yl, oxazolinyl, e.g. 2,3-dihydrooxazol-2-yl,
2,3-dihydrooxazol-3-yl, 2,3-dihydrooxazol-4-yl,
2,3-dihydrooxazol-5-yl, 2,5-dihydrooxazol-2-yl,
2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl,
4,5-dihydrooxazol-2-yl, 4,5-dihydrooxazol-4-yl or
4,5-dihydrooxazol-5-yl, thiazolinyl, e.g. 2,3-dihydrothiazol-2-yl,
2,3-dihydrothiazol-3-yl, 2,3-dihydrothiazol-4-yl,
2,3-dihydrothiazol-5-yl, 2,5-dihydrothiazol-2-yl,
2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl,
4,5-dihydrothiazol-2-yl, 4,5-dihydrothiazol-4-yl or
4,5-dihydrothiazol-5-yl, triazolinyl, e.g.
[1,2,3]-2,3-dihydrotriazol-1-yl, [1,2,3]-2,3-dihydrotriazol-2-yl,
[1,2,3]-2,3-dihydrotriazol-3-yl, [1,2,3]-2,3-dihydrotriazol-4-yl,
[1,2,3]-2,3-dihydrotriazol-5-yl, [1,2,3]-2,5-dihydrotriazol-1-yl,
[1,2,3]-2,5-dihydrotriazol-2-yl, [1,2,3]-2,5-dihydrotriazol-4-yl,
[1,2,3]-2,5-dihydrotriazol-5-yl, [1,2,3]-4,5-dihydrotriazol-1-yl,
[1,2,3]-4,5-dihydrotriazol-4-yl, [1,2,3]-4,5-dihydrotriazol-5-yl,
[1,2,4]-2,3-dihydrotriazol-1-yl, [1,2,4]-2,3-dihydrotriazol-2-yl,
[1,2,4]-2,3-dihydrotriazol-3-yl, [1,2,4]-2,3-dihydrotriazol-5-yl,
[1,2,4]-2,5-dihydrotriazol-1-yl, [1,2,4]-2,5-dihydrotriazol-2-yl,
[1,2,4]-2,5-dihydrotriazol-3-yl, [1,2,4]-2,5-dihydrotriazol-5-yl,
[1,2,4]-4,5-dihydrotriazol-1-yl, [1,2,4]-4,5-dihydrotriazol-3-yl,
[1,2,4]-4,5-dihydrotriazol-4-yl or [1,2,4]-4,5-dihydrotriazol-5-yl,
dihydropyridinyl, e.g. 1,2-dihydropyridin-1-yl,
1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl,
1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl,
1,2-dihydropyridin-6-yl, 1,4-dihydropyridin-1-yl,
1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl,
1,4-dihydropyridin-4-yl, 1,4-dihydropyridin-5-yl,
1,4-dihydropyridin-6-yl, 2,3-dihydropyridin-2-yl,
2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl,
2,3-dihydropyridin-5-yl or 2,3-dihydropyridin-6-yl,
dihydropyridinonyl, e.g. 1,2-dihydropyridin-2-on-1-yl,
1,2-dihydropyridin-2-on-3-yl, 1,2-dihydropyridin-2-on-4-yl,
1,2-dihydropyridin-2-on-5-yl or 1,2-dihydropyridin-2-on-6-yl,
tetrahydropyridinyl, e.g. 1,2,3,4-tetrahydropyridin-1-yl,
1,2,3,4-tetrahydropyridin-2-yl, 1,2,3,4-tetrahydropyridin-3-yl,
1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetrahydropyridin-5-yl,
1,2,3,4-tetrahydropyridin-6-yl, 1,2,5,6-tetrahydropyridin-1-yl,
1,2,5,6-tetrahydropyridin-2-yl, 1,2,5,6-tetrahydropyridin-3-yl,
1,2,5,6-tetrahydropyridin-4-yl, 1,2,5,6-tetrahydropyridin-5-yl,
1,2,5,6-tetrahydropyridin-6-yl, 3,4,5,6-tetrahydropyridin-2-yl,
3,4,5,6-tetrahydropyridin-3-yl, 3,4,5,6-tetrahydropyridin-4-yl,
3,4,5,6-tetrahydropyridin-5-yl or 3,4,5,6-tetrahydropyridin-6-yl,
tetrahydropyridinonyl, e.g. 1,2,3,4-tetrahydropyridin-2-on-1-yl,
1,2,3,4-tetrahydropyridin-2-on-3-yl,
1,2,3,4-tetrahydropyridin-2-on-4-yl,
1,2,3,4-tetrahydropyridin-2-on-5-yl,
1,2,3,4-tetrahydropyridin-2-on-6-yl,
1,2,5,6-tetrahydropyridin-2-on-1-yl,
1,2,5,6-tetrahydropyridin-2-on-3-yl,
1,2,5,6-tetrahydropyridin-2-on-4-yl,
1,2,5,6-tetrahydropyridin-2-on-5-yl or
1,2,5,6-tetrahydropyridin-2-on-6-yl, dehydromorpholinyl, e.g.
2,3-dehydromorpholin-2-yl, 2,3-dehydromorpholin-3-yl,
2,3-dehydromorpholin-4-yl, 2,3-dehydromorpholin-5-yl or
2,3-dehydromorpholin-6-yl, dehydrothiomorpholinyl, e.g.
2,3-dehydrothiomorpholin-2-yl, 2,3-dehydrothiomorpholin-3-yl,
2,3-dehydrothiomorpholin-4-yl, 2,3-dehydrothiomorpholin-5-yl or
2,3-dehydrothiomorpholin-6-yl and the like.
[0128] Examples of 5- or 6-membered heteroaromatic radicals
comprise 1-, 2- or 3-pyrrolyl, 2- or 3-furyl, 2- or 3-thienyl, 1-,
3-, 4- or 5-pyrazolyl, 1-, 2-, 4- or 5-imidazolyl, 2-, 3- or
5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 3- or 5-thiazolyl, 3-, 4-
or 5-isothiazolyl, 2- or 5-[1,3,4]oxadiazolyl, 4- or
5-[1,2,3]oxadiazolyl, 3- or 5-[1,2,4]oxadiazolyl, 2- or
5-[1,3,4]thiadiazolyl, 2- or 5-[1,3,4]thiadiazolyl, 4- or
5-[1,2,3]thiadiazolyl, 3- or 5-[1,2,4]thiadiazolyl, 1H--, 2H-- or
3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H--, 2H--, or
4H-1,2,4-triazolyl and 1H-- or 2H-tetrazolyl, 2-, 3-, or 4-pyridyl,
2-, 4- or 5-pyrimidinyl, pyrazinyl, 3- or 4-pyridazinyl or
2-[1,3,5]triazinyl.
[0129] Examples of a phenyl ring fused to phenyl, to a saturated or
partly unsaturated 5- or 6-membered carbocyclic ring or to a
saturated, partly unsaturated or aromatic heterocyclic ring which
contains as ring members 1, 2 or 3 heteroatoms selected from O, S
and N and optionally 1 or 2 CO groups comprise naphthyl, indenyl,
indanyl, 1,2- or 2,3-dihydronaphthyl, tetralinyl, indolyl,
2,3-dihydroindolyl, indazolyl, indoxylyl, oxindolyl,
benzimidazolyl, 2,3-dihydrobenzimidazolyl, cumaronyl
(benzo[b]furanyl), 2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl,
benzo-1,4-dioxanyl, benzoxazolyl, 2,3-dihydrobenzoxazolyl,
benzo[b]thienyl, 2,3-dihydrobenzothienyl, benzothiazolyl,
2,3-dihydrobenzothiazolyl, benzoxathiazolyl, benzoxadiazolyl,
benzothiadiazolyl, benzoxazinyl, dihydrobenzoxazinyl, quinolinyl,
isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl,
tetrahydroisoquinolinyl, chromenyl, chromonyl, icochromenyl,
chromanyl, chromanonyl, isochromanyl and the like. This fused
system may be bonded to the remainder of the molecule via carbon
atoms of the phenyl moiety (this corresponds to the definition
"phenyl fused to phenyl or a carbocyclic or heterocyclic ring) or
via ring atoms (C-- or Natoms) of the ring fused to phenyl (this
corresponds to the definition "heterocyclic ring fused to
phenyl).
[0130] Examples of this fused system being for its part fused to
phenyl are anthracenyl, phenanthrenyl, acenaphthenyl,
dihydroacenaphthenyl, fluorenyl, carbazolyl, dibenzofuranyl,
dibenzothienyl, acridinyl, carbazinyl (acridanyl), phenazinyl,
9,10-dihydrophenazinyl, dibenzomorpholinyl (phenoxazinyl) and
dibenzothiomorpholinyl (phenothiazinyl).
[0131] If R.sup.8 and R.sup.9 form together with the CH group to
which they are bound a CH-bound 5- or 6-membered saturated or
partly unsaturated carbocyclic ring which is fused to a phenyl
group, this is for example indanyl, such as indan-1-yl, indenyl,
such as inden-3-yl, indanonyl, such as indan-2-on-1-yl or
indan-3-on-1-yl, tetralinyl, such as tetralin-1-yl, or
dihydronaphthyl, such as 1,4-dihydronaphth-1-yl or
2,3-dihydronaphth-1-yl.
[0132] If R.sup.8 and R.sup.9 form together with the CH group to
which they are bound a CH-bound 5- or 6-membered saturated or
partly unsaturated carbocyclic ring which is fused to a 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which contains as ring members 1, 2 or 3 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups, this is for
example 2,3-cyclopentenopyridyl, 2,3-cyclohexenopyridyl,
4,5,6,7-tetrahydroindolyl, 4,5,6,7-tetrahydrobenzimidazolyl and the
like.
[0133] If R.sup.8 and R.sup.9 form together with the CH group to
which they are bound a CH-bound 5- or 6-membered saturated or
partly unsaturated heterocyclic ring which is fused to a phenyl
group, this is for example 2,3-dihydroindolyl, e.g.
2,3-dihydroindol-2-yl or 2,3-dihydroindol-3-yl, indoxylyl, e.g.
indoxyl-2-yl, oxindolyl, e.g. oxindol-3-yl,
2,3-dihydrobenzimidazolyl, e.g. 2,3-dihydrobenzimidazol-2-yl,
2,3-dihydrobenzofuranyl, e.g. 2,3-dihydrobenzofuran-2-yl or
2,3-dihydrobenzofuran-3-yl, 1,3-benzodioxolyl, e.g.
1,3-benzodioxol-2-yl, benzo-1,4-dioxanyl, e.g.
benzo-1,4-dioxan-2-yl, 2,3-dihydrobenzoxazolyl, e.g.
2,3-dihydrobenzoxazol-2-yl, 2,3-dihydrobenzothienyl, e.g.
2,3-dihydrobenzothien-2-yl or 2,3-dihydrobenzothien-3-yl,
2,3-dihydrobenzothiazolyl, e.g. 2,3-dihydrobenzothiazol-2-yl,
1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl,
dihydro-1,4-benzoxazinyl, dihydroquinolinyl, e.g.
1,2-dihydroquinolin-2-yl, 3,4-dihydroquinolin-3-yl or
3,4-dihydroquinolin-4-yl, tetrahydroquinolinyl, e.g.
1,2,3,4-tetrahydroquinolin-2-yl, 1,2,3,4-tetrahydroquinolin-3-yl or
1,2,3,4-tetrahydroquinolin-4-yl, dihydroisoquinolinyl, e.g.
1,2-dihydroisoquinolin-1-yl, 3,4-dihydroisoquinolin-3-yl or
3,4-dihydroisoquinolin-4-yl, tetrahydroisoquinolinyl, e.g.
1,2,3,4-tetrahydroisoquinolin-1-yl,
1,2,3,4-tetrahydroisoquinolin-3-yl or
1,2,3,4-tetrahydroisoquinolin-4-yl, 2,3-dihydroquinoxalinyl, e.g.
2,3-dihydroquinoxalin-2-yl, tetrahydroquinoxalinyl, e.g.
1,2,3,4-tetrahydroquinoxalin-2-yl, dihydroquinazolinyl, e.g.
1,2-dihydroquinazolin-2-yl or 3,4-dihydroquinazolin-4-yl,
tetrahydroquinazolinyl, e.g. 1,2,3,4-tetrahydroquinazolin-2-yl or
1,2,3,4-tetrahydroquinazolin-4-yl, dihydrocinnolinyl, e.g.
3,4-dihydrocinnolin-3-yl or 3,4-dihydrocinnolin-4-yl,
tetrahydrocinnolinyl, e.g. 1,2,3,4-tetrahydrocinnolin-3-yl or
1,2,3,4-tetrahydrocinnolin-4-yl, chromenyl, e.g. chromen-4-yl,
isochromenyl, e.g. isochromen-1-yl, chromanyl, e.g. chroman-2-yl,
chroman-3-yl or chroman-4-yl, chroman-4-onyl, e.g.
chroman-4-on-2-yl or chroman-4-on-3-yl, or isochromanyl, e.g.
isochroman-1-yl, isochroman-3-yl or isochroman-4-yl.
[0134] If R.sup.12 and R.sup.13, together with the nitrogen atom to
which they are bound, form a 4-, 5- or 6-membered saturated, partly
unsaturated or aromatic heterocyclic ring which may contain as ring
members 1 or 2 further heteroatoms selected from O, S and N and/or
1 or 2 carbonyl groups, this is an N-bound 4-, 5- or 6-membered
saturated, partly unsaturated or aromatic heterocyclic ring which
may contain further heteroatoms, in particular one further N, O or
S or one further N and an O or an S atom. Additionally or
alternatively the heterocyclic ring may contain 1 or 2 carbonyl
groups. Examples of such rings are 1-azetidinyl, 1-pyrrolidinyl,
pyrrolidin-2-on-1-, pyrrolidin-2,5-dion-1-yl, 1-pyrrolinyl,
1-pyrrolyl, 1-pyrazolidinyl, 1-pyrazolinyl, 1-pyrazolyl,
1-imidazolidinyl, imidazolidin-2-on-1-yl, 1-imidazolinyl,
1-imidazolyl, 3-oxazolidinyl, 3-thiazolidinyl,
1-[1,2,3]-1H-triazolidinyl, 4-[1,2,4]-4-H-triazolidinyl,
1-[1,2,3]-1H-triazolyl, 4-[1,2,4]-4-H-triazolyl, 1-piperidinyl,
1-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl and the like.
[0135] The below remarks to suitable and preferred embodiments of
the variables are to be understood to refer the single variable as
well as in particular in combination with preferred meanings of
other variables.
[0136] In compounds I, R.sup.1 and R.sup.2 are independently of
each other preferably H, halogen or C.sub.1-C.sub.4-alkyl, more
preferably H, fluorine, chlorine or methyl, in particular H or
methyl and specifically H. Preferably, one of R.sup.1 and R.sup.2
is H and the other is selected from H, halogen and
C.sub.1-C.sub.4-alkyl and more preferably from H, fluorine,
chlorine and methyl.
[0137] Preferably, R.sup.3 and R.sup.4 are independently of each
other H, halogen, C.sub.1-C.sub.4-alkyl or
C.sub.1-C.sub.4-haloalkyl. In a preferred embodiment, one of
R.sup.3 and R.sup.4 is H and the other is H, halogen,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl. More
preferably, R.sup.3 and R.sup.4 are independently of each other H,
halogen or C.sub.1-C.sub.4-alkyl and even more preferably, one of
R.sup.3 and R.sup.4 is H and the other is H, halogen or
C.sub.1-C.sub.4-alkyl. Preferably, halogen is fluorine and
C.sub.1-C.sub.4-alkyl is methyl. In particular R.sup.3 and R.sup.4
are independently of each other H or C.sub.1-C.sub.4alkyl,
particularly methyl, and even more preferably, one of R.sup.3 and
R.sup.4 is H and the other is H or C.sub.1-C.sub.4-alkyl,
particularly methyl. Specifically, both R.sup.3 and R.sup.4 are
H.
[0138] Preferably, R.sup.5 and R.sup.6 are independently of each
other H, halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-haloalkoxy. In a
preferred embodiment, one of R.sup.5 and R.sup.6 is H and the other
is H, halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy or C.sub.ra.sub.t-haloalkoxy. More
preferably, R.sup.5 and R.sup.6 are independently of each other H,
halogen, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4alkoxy and even
more preferably, one of R.sup.5 and R.sup.6 is H and the other is
H, halogen, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy.
Preferably, halogen is fluorine, C.sub.1-C.sub.4-alkyl is methyl
and C.sub.1-C.sub.4-alkoxy is methoxy. It is preferred that the
substituent(s) which is (are) different from H be located ortho
relative to the CO--NR.sup.7 group. Specifically, both R.sup.5 and
R.sup.6 are H.
[0139] R.sup.7 is preferably H or C.sub.1-C.sub.8-alkyl, more
preferably H or C.sub.1-C.sub.4-alkyl, even more preferably H,
methyl or ethyl and in particular H or methyl. Specifically,
R.sup.7 is H.
[0140] In groups R.sup.8, X is preferably a single bond, CH.sub.2,
CH(OH) or CH.sub.2CH.sub.2. More preferably, X is a single bond,
CH.sub.2 or CH(OH) and in particular a single bond or CH.sub.2.
[0141] W is preferably selected from phenyl, naphthyl, anthracenyl,
phenanthrenyl, indenyl, indanyl, dihydronaphthyl, tetralinyl,
indolyl, 2,3-dihydroindolyl, indoxylyl, oxindolyl, indazolyl,
2,3-dihydroindazolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl,
cumaronyl (benzo[b]furanyl), 2,3-dihydrobenzofuranyl,
benzo-1,3-dioxyl, benzo-1,4-dioxanyl, benzoxazolyl,
2,3-dihydrobenzoxazolyl, benzo[b]thienyl, 2,3-dihydrobenzothienyl,
benzothiazolyl, 2,3-dihydrobenzothiazolyl, quinolinyl,
isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromenyl,
chromenonyl, isochromenyl, chromanyl, chromanonyl, isochromanyl,
acenaphthenyl, dihydroacenaphthenyl, fluorenyl, carbazolyl,
dibenzofuranyl, dibenzothienyl, acridinyl, carbazinyl (acridanyl),
phenazinyl, 9,10-dihydrophenazinyl, dibenzomorpholinyl
(phenoxazinyl), dibenzothiomorpholinyl (phenothiazinyl), where the
44 last-mentioned radicals are bonded via the phenyl moiety of the
fused system to the group X; or W is a saturated, partly
unsaturated or aromatic 5- or 6-membered heterocyclic ring
containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups as ring members or is a
saturated, partly unsaturated or aromatic 5- or 6-membered
heterocyclic ring containing 1 or 2 heteroatoms selected from O, S
and N and optionally 1 or 2 carbonyl groups as ring members which
is fused to a phenyl ring and which is bonded via the heterocyclyl
moiety of the fused system to the group X, where the above radicals
may carry 1, 2, 3, 4 or 5 substituents R.sup.10 as defined
above.
[0142] Suitable saturated, partly unsaturated or aromatic 5- or
6-membered heterocyclic ring containing 1, 2, 3 or 4 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members are the 5- or 6-membered saturated heterocyclic rings
containing 1, 2, 3 or 4 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups, the 5- or 6-membered partly
unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups and
the 5- or 6-membered heteroaromatic radicals listed above.
[0143] Suitable saturated, partly unsaturated or aromatic 5- or
6-membered heterocyclic rings containing 1 or 2 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members which are fused to a phenyl ring and which are bonded
via the heterocyclyl moiety of the fused system to the group X are
the above-listed fused systems which are however bound via the
heterocyclic ring, in particular indol-1-yl, indol-2-yl,
indol-3-yl, 2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl,
2,3-dihydroindol-3-yl, indoxyl-1-yl, indoxyl-2-yl, oxindol-1-yl,
oxindol-3-yl, indazol-1-yl, indazol-3-yl, 2,3-dihydroindazol-1-yl,
2,3-dihydroindazol-2-yl, 2,3-dihydroindazol-3-yl,
benzimidazol-1-yl, benzimidazol-2-yl, 2,3-dihydrobenzimidazol-1-yl,
2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-3-yl,
cumaron-2-yl(benzo[b]furan-2-yl), cumaron-3-yl(benzo[b]furan-4-yl),
2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl,
benzo-1,3-diox-2-yl, benzo-1,4-dioxan-2-yl, benzoxazol-2-yl,
2,3-dihydrobenzoxazol-2-yl, 2,3-dihydrobenzoxazol-3-yl,
benzo[b]thien-2-yl, benzo[b]thien-3-yl, 2,3-dihydrobenzothien-2-yl,
2,3-dihydrobenzothien-3-yl, benzothiazol-2-yl,
2,3-dihydrobenzothiazol-2-yl, 2,3-dihydrobenzothiazol-3-yl,
[1,3,4]-(1H)-triazolo[.alpha.]pyrimidyl, quinolin-2-yl,
quinolin-3-yl, quinolin-4-yl, isoquinolin-1-yl, isoquinolin-3-yl,
isoquinolin-4-yl, quinoxalin-2-yl, quinazolin-2-yl,
quinazolin-4-yl, cinnolin-3-yl, cinnolin-4-yl, chromen-2-yl,
chromen-3-yl, chromen-4-yl, chromen-4-on-2-yl, chromen-4-on-3-yl,
isochromen-1-yl, isochromen-3-yl, isochromen-4-yl, chroman-2-yl,
chroman-3-yl, chroman-4-yl, chroman-4-on-2-yl, chroman-4-on-3-yl,
isochroman-1-yl, isochroman-3-yl or isochroman-4-yl.
[0144] Suitable saturated, partly unsaturated or aromatic 5- or
6-membered heterocyclic rings containing 1 or 2 heteroatoms
selected from O, S and N and optionally 1 or 2 carbonyl groups as
ring members which are fused to a 5- or 6-membered saturated,
partly unsaturated or aromatic heterocyclic ring which contains as
ring members 1, 2 or 3 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups are for example azolopyridine or
azolopyrimidine radicals, such as pyrrolo-[2,3-a]-pyridyl,
pyrrolo-[2,3-b]-pyridyl, imidazolo-[2,3-a]pyridyl,
[1,3,4]-(1H)-triazolo[1,2-a]pyridyl and the like, the latter
radical being preferred.
[0145] More preferably, W is selected from phenyl, naphthyl,
anthracenyl, indanyl, tetralinyl, fluoren-1-yl, fluoren-2-yl,
fluoren-3-yl, fluoren-4-yl, dihydroacenaphthen-1-yl,
dihydroacenaphthen-2-yl, dihydroacenaphthen-3-yl, a 5- or
6-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms
selected from O, S and N as ring members and a saturated, partly
unsaturated or aromatic 5- or 6-membered heterocyclic ring
containing 1 or 2 heteroatoms selected from O, S and N and
optionally 1 or 2 carbonyl groups as ring members which is fused to
a phenyl ring and which is bound via the heterocyclic moiety or via
the phenyl moiety to the group X, where the heterocyclic ring for
its part may be fused to a second phenyl ring. These radicals may
carry 1, 2, 3, 4 or 5 substituents R.sup.10 as defined above.
[0146] Preferably, the fused system (=saturated, partly unsaturated
or aromatic 5- or 6-membered heterocyclic ring containing 1 or 2
heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl
groups as ring members which is fused to one or two phenyl rings
and which is bound via the heterocyclic moiety or via a phenyl
moiety to the group X) is selected from indol-1-yl, indol-2-yl,
indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl,
2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl,
2,3-dihydroindol-3-yl, 2,3-dihydroindol-4-yl,
2,3-dihydroindol-5-yl, 2,3-dihydroindol-6-yl,
2,3-dihydroindol-7-yl, benzofuran-2-yl, benzofuran-3-yl,
benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl,
2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl,
2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl,
2,3-dihydrobenzofuran-6-yl, 2,3-dihydrobenzofuran-7-yl,
1,3-benzodiox-2-yl, 1,3-benzodiox-4-yl, 1,3-benzodiox-5-yl,
1,4-benzodioxan-2-yl, 1,4-benzodioxan-5-yl, 1,4-benzodioxan-6-yl,
benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl,
benzothien-6-yl, benzothien-7-yl, 2,3-dihydrobenzothien-2-yl,
2,3-dihydrobenzothien-3-yl, 2,3-dihydrobenzothien-4-yl,
2,3-dihydrobenzothien-5-yl, 2,3-dihydrobenzothien-6-yl,
2,3-dihydrobenzothien-7-yl, benzimidazol-1-yl, benzimidazol-2-yl,
benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl,
benzimidazol-7-yl, 2,3-dihydrobenzimidazol-1-yl,
2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-4-yl,
2,3-dihydrobenzimidazol-5-yl, 2,3-dihydrobenzimidazol-6-yl,
2,3-dihydrobenzimidazol-7-yl, benzoxazol-2-yl, benzoxazol-4-yl,
benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-yl,
benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl,
benzothiazol-6-yl, benzothiazol-7-yl, carbazol-1-yl, carbazol-2-yl,
carbazol-3-yl, carbazol-4-yl, dibenzofuran-1-yl, dibenzofuran-2-yl,
dibenzofuran-3-yl, dibenzofuran-4-yl, phenothiazin-1-yl,
phenothiazin-2-yl, phenothiazin-3-yl and phenothiazin-4-yl, where
these radicals may carry 1, 2, 3, 4 or 5 substituents R.sup.10 as
defined above.
[0147] Preferably, the 5- or 6-membered heteroaromatic ring
containing 1, 2 or 3 heteroatoms selected from O, S and N as ring
members is selected from pyrrolyl, such as pyrrol-1-yl, pyrrol-2-yl
or pyrrol-3-yl, furanyl, such as furan-2-yl or furan-3-yl, thienyl,
such as thien-2-yl or thien-3-yl, pyrazolyl, such as pyrazol-1-yl,
pyrazol-3-yl, pyrazol-4-yl or pyrazol-5-yl, imidazolyl, such as
imidazol-1-yl, imidazol-2-yl, imidazol-4-yl or imidazol-5-yl,
oxazolyl, such as oxazol-2-yl, oxazol-4-yl or oxazol-5-yl,
isoxazolyl, such as isoxazol-3-yl, isoxazol-4-yl or isoxazol-5-yl,
thiazolyl, such as thiazol-2-yl, thiazol-4-yl or thiazol-5-yl,
isothiazolyl, such as isothiazol-3-yl, isothiazol-4-yl or
isothiazol-5-yl, triazolyl, such as [1,2,3]-(1H)-triazol-1-yl,
[1,2,3]-(1H)-triazol-4-yl, [1,2,3]-(1H)-triazol-5-yl,
[1,2,3]-(2H)-triazol-2-yl, [1,2,3]-(2H)-triazol-4-yl,
[1,2,3]-(2H)-triazol-5-yl, [1,2,4]-(1H)-triazol-1-yl,
[1,2,4]-(1H)-triazol-3-yl, [1,2,4]-(1H)-triazol-5-yl,
[1,2,4]-(4H)-triazol-3-yl, [1,2,4]-(4H)triazol-4-yl or
[1,2,4]-(4H)-triazol-5-yl, oxadiazolyl, such as
[1,3,4]oxadiazol-2-yl, [1,3,4]oxadiazol-5-yl,
[1,2,3]oxadiazol-4-yl, [1,2,3]oxadiazol-5-yl,
[1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl,
[2,1,5]-oxadiazol-3-yl or [2,1,5]-oxadiazol-4-yl, thiadiazolyl,
such as [1,3,4]thiadiazol-2-yl, [1,3,4]thiadiazol-5-yl,
[1,2,3]thiadiazol-4-yl, [1,2,3]thiadiazol-5-yl,
[1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl,
[2,1,5]thiadiazol-3-yl or [2,1,5]thiadiazol-4-yl, pyridyl, such as
pyrid-2-yl, pyrid-3-yl or pyrid-4-yl, pyrimidyl, such as
pyrimid-2-yl, pyrimid-4-yl or pyrimid-5-yl, pyrazinyl and
pyridazinyl, such as pyridazin-3-yl or pyridazin-4-yl. Among these,
heteroaromatic rings which are not bound via a nitrogen atom are
preferred.
[0148] More preferred are furanyl, such as furan-2-yl or
furan-3-yl, thienyl, such as thien-2-yl or thien-3-yl, pyrazolyl,
such as pyrazol-3-yl, pyrazol-4-yl or pyrazol-5-yl, imidazolyl,
such as imidazol-2-yl, imidazol-4-yl or imidazol-5-yl, oxazolyl,
such as oxazol-2-yl, oxazol-4-yl or oxazol-5-yl, isoxazolyl, such
as isoxazol-3-yl, isoxazol-4-yl or isoxazol-5-yl, thiazolyl, such
as thiazol-2-yl, thiazol-4-yl or thiazol-5-yl, isothiazolyl, such
as isothiazol-3-yl, isothiazol-4-yl or isothiazol-5-yl, triazolyl,
such as [1,2,3]-(1H)-triazol-4-yl, [1,2,3]-(1H)-triazol-5-yl,
[1,2,3]-(2H)-triazol-4-yl, [1,2,3]-(2H)-triazol-5-yl,
[1,2,4]-(1H)-triazol-3-yl, [1,2,4]-(1H)-triazol-5-yl,
[1,2,4]-(4H)-triazol-3-yl or [1,2,4]-(4H)-triazol-5-yl,
oxadiazolyl, such as [1,3,4]oxadiazol-2-yl, [1,3,4]oxadiazol-5-yl,
[1,2,3]oxadiazol-4-yl, [1,2,3]oxad iazol-5-yl,
[1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl,
[2,1,5]-oxadiazol-3-yl or [2,1,5]-oxadiazol-4-yl, pyridyl, such as
pyrid-2-yl, pyrid-3-yl or pyrid-4-yl, and pyrimidyl, such as
pyrimid-2-yl, pyrimid-4-yl or pyrimid-5-yl. Particularly preferred
is pyridyl.
[0149] Thus, W is even more preferably selected from phenyl,
naphthyl, anthracenyl, indanyl, tetralinyl, a 5- or 6-membered
heteroaromatic ring containing 1, 2 or 3 heteroatoms selected from
O, S and N as ring members (which is preferably selected from the
heteroaromatic rings mentioned above (and which is in particular
pyridyl), indol-1-yl, indol-2-yl, indol-3-yl, indol-4-yl,
indol-5-yl, indol-6-yl, indol-7-yl, 2,3-dihydroindol-1-yl,
2,3-dihydroindol-2-yl, 2,3-dihydroindol-3-yl,
2,3-dihydroindol-4-yl, 2,3-dihydroindol-5-yl,
2,3-dihydroindol-6-yl, 2,3-dihydroindol-7-yl, benzofuran-2-yl,
benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl,
benzofuran-7-yl, 2,3-dihydrobenzofuran-2-yl,
2,3-dihydrobenzofuran-3-yl, 2,3-dihydrobenzofuran-4-yl,
2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-6-yl,
2,3-dihydrobenzofuran-7-yl, 1,3-benzodiox-2-yl, 1,3-benzodiox-4-yl,
1,3-benzodiox-5-yl, 1,4-benzodioxan-2-yl, 1,4-benzodioxan-5-yl,
1,4-benzodioxan-6-yl, benzothien-2-yl, benzothien-3-yl,
benzothien-4-yl, benzothien-5-yl, benzofthien-6-yl,
benzothien-7-yl, 2,3-dihydrobenzothien-2-yl,
2,3-dihydrobenzothien-3-yl, 2,3-dihydrobenzothien-4-yl,
2,3-dihydrobenzothien-5-yl, 2,3-dihydrobenzothien-6-yl,
2,3-dihydrobenzothien-7-yl, benzimidazol-1-yl, benzimidazol-2-yl,
benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl,
benzimidazol-7-yl, 2,3-dihydrobenzimidazol-1-yl,
2,3-dihydrobenzimidazol-2-yl, 2,3-dihydrobenzimidazol-4-yl,
2,3-dihydrobenzimidazol-5-yl, 2,3-dihydrobenzimidazol-6-yl,
2,3-dihydrobenzimidazol-7-yl, benzoxazol-2-yl, benzoxazol-4-yl,
benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-yl,
benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl,
benzothiazol-6-yl, benzothiazol-7-yl, fluoren-1-yl, fluoren-2-yl,
fluoren-3-yl, fluoren-4-yl, carbazol-1-yl, carbazol-2-yl,
carbazol-3-yl, carbazol-4-yl, dibenzofuran-1-yl, dibenzofuran-2-yl,
dibenzofuran-3-yl, dibenzofuran-4-yl, phenothiazin-1-yl,
phenothiazin-2-yl, phenothiazin-3-yl, phenothiazin-4-yl,
dihydroacenaphthen-1-yl, dihydroacenaphthen-2-yl and
dihydroacenaphthen-3-yl, where these radicals may carry 1, 2, 3, 4
or 5 substituents R.sup.10 as defined above.
[0150] Particularly preferably, W is selected from phenyl,
naphthyl, a 5- or 6-membered heteroaromatic ring containing 1, 2 or
3 heteroatoms selected from O, S and N as ring members (which is
preferably selected from the heteroaromatic rings mentioned above)
and a saturated, partly unsaturated or aromatic 5- or 6-membered
heterocyclic ring containing 1 or 2 heteroatoms selected from O, S
and N and optionally 1 or 2 carbony) groups as ring members which
is fused to a phenyl ring and which is bonded via the heterocyclyl
moiety or via the phenyl moiety of the fused system to the group X,
where the above radicals may carry 1, 2, 3, 4 or 5 substituents
R.sup.10 as defined above. Preferably, the heteroaromatic ring is
pyridyl. Preferably, the heterocyclic ring fused to phenyl is
selected from indol-1-yl, indol-2-yl, indol-3-yl,
2,3-dihydroindol-1-yl, 2,3-dihydroindol-2-yl,
2,3-dihydroindol-3-yl, benzofuran-2-yl, benzofuran-3-yl,
2,3-dihydrobenzofuran-2-yl, 2,3-dihydrobenzofuran-3-yl,
1,3-benzodiox-2-yl, 1,4-benzodioxan-2-yl, benzo-1,4-dioxan-5-yl,
benzo-1,4-dioxan-6-yl, benzothien-2-yl, benzothien-3-yl,
benzimidazol-2-yl and benzothiazol-2-yl and more preferably from
indol-2-yl, indol-3-ylbenzo-1,4-dioxan-5-yl and
benzo-1,4-dioxan-6-yl. These radicals W may carry 1, 2, 3, 4 or 5
substituents R.sup.10 as defined above.
[0151] R.sup.10 as optional substituent of the cyclic radical in
group W is preferably selected from halogen, hydroxyl, cyano,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.6-alkoxy where the alkyl moiety may carry a CN group,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio,
C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfonyl,
C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.1-C.sub.4-alkylcarbonyl,
C.sub.1-C.sub.4-haloalkylcarbonyl,
C.sub.1-C.sub.4-alkylcarbonyloxy,
C.sub.1-C.sub.4-haloalkylcarbonyloxy,
C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl,
C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkenyloxy,
C.sub.3-C.sub.6-cycloalkyl, phenyl, benzyl, phenoxy, benzoxy,
phenoxymethyl, phenylthio, phenylsulfonyl, where the phenyl moiety
in the 7 last-mentioned radicals may carry 1, 2, 3, 4 or 5
substituents independently selected from halogen, OH,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, phenyl,
benzyl, phenoxy and benzoxy; 5- or 6-membered heteroaryl containing
1, 2, 3 or 4 heteroatoms selected from O, S and N as ring members,
where the heteroaryl ring may carry 1, 2, 3 or 4 substituents
independently selected from halogen, OH, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkylthio and
C.sub.1-C.sub.4-haloalkylthio; aminocarbonyl and NR.sup.aR.sup.b,
where R.sup.a and R.sup.b are independently selected from H,
C.sub.1-C.sub.6-alkyl, formyl and
C.sub.1-C.sub.4-alkylcarbonyl.
[0152] More preferably, R.sup.10 is selected from halogen,
hydroxyl, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy,
C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, phenyl,
benzyl, phenoxy and benzoxy (C.sub.6H.sub.5CH.sub.2O).
[0153] In the radical R.sup.9, Y is preferably CH.sub.2, CH(OH),
CH(phenyl) or CH.sub.2CH.sub.2. More preferably, Y is CH.sub.2,
CH(OH) or CH(phenyl) and even more preferably is CH.sub.2 or
CH(OH). In particular, Y is CH.sub.2.
[0154] Z is preferably hydrogen, halogen, OR.sup.11,
NR.sup.12R.sup.13 or phenyl which may carry 1, 2, 3 or 4
substituents R.sup.15 and more preferably hydrogen, OR.sup.11,
NR.sup.12R.sup.13 or phenyl which may carry 1, 2, 3 or 4
substituents R.sup.15.
[0155] R.sup.11 is preferably H or C.sub.1-C.sub.4-alkyl, more
preferably H, methyl or ethyl and in particular H or methyl.
[0156] In a preferred embodiment of the invention, R.sup.12 and
R.sup.13 are independently of each other selected from hydrogen,
C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl,
C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl,
C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl,
C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl,
phenylcarbonyl, benzylcarbonyl, phenylsulfonyl and benzylsulfonyl,
where the phenyl moiety in the six last-mentioned radicals may
carry 1, 2 or 3, preferably 1 or 2 substituents, in particular 1
substituent selected from halogen, hydroxyl, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and
C.sub.1-C.sub.4-haloalkoxy, or R.sup.12 and R.sup.13, together with
the nitrogen atom to which they are bound, form a 4-, 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which may contain as ring members 1 or 2 further heteroatoms
selected from O, S and N and/or 1 or 2 carbonyl groups, and where
the heterocyclic ring may carry 1, 2 or 3 substituents selected
from halogen, hydroxyl, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and
C.sub.1-C.sub.4-haloalkoxy.
[0157] Preferably, the above phenyl substituents are selected from
halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, more
preferably from C.sub.1-C.sub.4-alkyl and C.sub.1-C.sub.4-haloalkyl
and in particular from methyl.
[0158] In a more preferred embodiment of the invention, R.sup.12
and R.sup.13 are independently of each other selected from
hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl,
C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl,
C.sub.1-C.sub.4-alkylsulfonyl and phenylsulfonyl, where the phenyl
moiety in the last-mentioned radical may carry 1, 2 or 3,
preferably 1 or 2 substituents, in particular 1 substituent as
defined above, or R.sup.12 and R.sup.13, together with the nitrogen
atom to which they are bound, form a 4-, 5- or 6-membered
saturated, partly unsaturated or aromatic heterocyclic ring which
may contain as ring members 1 or 2 further heteroatoms selected
from O, S and N and/or 1 or 2 carbonyl groups, and where the
heterocyclic ring may carry 1, 2 or 3 substituents selected from
halogen, hydroxyl, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and
C.sub.1-C.sub.4-haloalkoxy.
[0159] If R.sup.12 and R.sup.13, together with the nitrogen atom to
which they are bound, form a 4-, 5- or 6-membered ring, preferably
a 5- or 6-membered ring, this is preferably saturated or aromatic.
Preferably, the ring contains apart the nitrogen atom via which it
is bound to the group Y no or one further heteroatom. The further
heteroatom(s) is are preferably selected from O and N. If the ring
is substituted, the substituent(s) may be bound at a C or at an N
atom. Preferred ring substituents are selected from halogen,
C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, more
preferably from C.sub.1-C.sub.4-alkyl and
C.sub.1-C.sub.4-haloalkyl, more preferably from
C.sub.1-C.sub.4-alkyl and in particular methyl.
[0160] In an alternatively preferred embodiment, R.sup.8 and
R.sup.9, together with the CH group to which they are bonded, form
a CH-bound saturated or partly unsaturated 5- or 6-membered
carbocyclic ring which may contain 1 or 2 carbonyl groups as ring
members or a saturated or partly unsaturated 5- or 6-membered
heterocyclic ring, where the heterocyclic ring contains 1 or 2
heteroatoms selected from O, S and N and optionally 1 carbonyl
group as ring members, where the carbocyclic ring and the
heterocyclic ring are fused to a phenyl ring or to a 5- or
6-membered saturated, partly unsaturated or aromatic heterocyclic
ring which contains as ring members 1, 2 or 3 heteroatoms selected
from O, S and N and optionally 1 or 2 carbonyl groups, where the
carbocyclic ring and the heterocyclic ring and/or the ring fused
thereto may carry 1, 2 or 3 substituents R.sup.15, with the proviso
that in case the carbocyclic ring is fused to a phenyl ring, the
points of fusion are not in the 3,4-position, relative to the
1-position of the bond to the group NR.sup.7.
[0161] Suitable fused systems are those listed above. Examples are
indanyl, such as indan-1-yl, indenyl, such as inden-3-yl,
indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl,
such as tetralin-1-yl, dihydronaphthyl, such as
1,2-dihydronaphth-1-yl or 1,4-dihydronaphth-1-yl,
2,3-dihydroindolyl, indoxylyl, oxindolyl,
2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzofuranyl,
benzo-1,3-dioxyl, benzo-1,4-dioxanyl, 2,3-dihydrobenzoxazolyl,
2,3-dihydrobenzothienyl, 2,3-dihydrobenzothiazolyl,
1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl,
dihydro-1,4-benzoxazinyl, 1,2- and 3,4-dihydroquinolinyl,
1,2,3,4-tetrahydroquinolinyl, 1,2- and 3,4-dihydroisoquinolinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2- and 3,4-dihydroquinoxalinyl,
1,2,3,4-tetrahydroquinoxalinyl, 1,2- and 3,4-dihydroquinazolinyl,
1,2,3,4-tetrahydroquinazolinyl, 1,2- and 3,4-dihydrocinnolinyl,
1,2,3,4-tetahydrocinnolinyl, chromenyl, chromonyl, isochromenyl,
chromanyl, chromanonyl, isochromanyl, pyrrolidino-[2,3-a]-pyridyl,
pyrrolidinoo-[2,3-b]-pyridyl, iidinomidazolo-[2,3-a]pyridyl,
[1,3,4]-(1H)-triazolidino[1,2-a]pyridyl, 2,3-cyclopentenopyridyl,
2,3-cyclohexenopyridyl, 4,5,6,7-tetrahydroindolyl,
4,5,6,7-tetrahydrobenzimidazolyl and the like.
[0162] In this embodiment, it is preferred that R.sup.8 and
R.sup.9, together with the CH group to which they are bonded, form
a CH-bound saturated or partly unsaturated 5- or 6-membered
carbocyclic ring which may contain 1 or 2 carbonyl groups as ring
members or a saturated or partly unsaturated 5- or 6-membered
heterocyclic ring, where the heterocyclic ring contains 1 or 2
heteroatoms selected from O, S and N and optionally 1 carbonyl
group as ring members, where the carbocyclic ring and the
heterocyclic ring are fused to a phenyl ring, where the carbocyclic
ring and the heterocyclic ring and/or the phenyl ring fused thereto
may carry 1, 2 or 3, preferably 1, substituents R.sup.15, with the
proviso that in case it is the carbocyclic ring which is fused to a
phenyl ring, the points of fusion are not in the 3,4-position,
relative to the 1-position of the bond to the group NR.sup.7.
[0163] More preferably, R.sup.8 and R.sup.9, together with the CH
group to which they are bonded, form a CH-bound saturated 5- or
6-membered carbocyclic ring which may contain 1 or 2 carbonyl
groups as ring members or a saturated or partly unsaturated 5- or
6-membered heterocyclic ring, where the heterocyclic ring contains
1 or 2, preferably 1 heteroatoms selected from O, S and N,
preferably O, and optionally 1 carbonyl group as ring members,
where the carbocyclic ring and the heterocyclic ring are fused to a
phenyl ring where the carbocyclic ring and the heterocyclic ring
and/or the phenyl ring fused thereto may carry 1, 2 or 3,
preferably 1, substituents R.sup.15, with the proviso that in case
it is the carbocyclic ring which is fused to a phenyl ring, the
points of fusion are not in the 3,4-position, relative to the
1-position of the bond to the group NR.sup.7.
[0164] In particular, this fused system is selected from indanyl,
such as indan-1-yl, indenyl, such as inden-3-yl, indanonyl, such as
indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl, such as
tetralin-1-yl, dihydronaphthyl, such as 1,2-dihydronaphth-1-yl or
1,4-dihydronaphth-1-yl, 2,3-dihydroindolyl, indoxylyl, oxindolyl,
2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzofuranyl,
benzo-1,3-dioxyl, benzo-1,4-dioxanyl, 2,3-dihydrobenzoxazolyl,
2,3-dihydrobenzothienyl, 2,3-dihydrobenzothiazolyl,
1,3-benzoxazinyl, 1,4-benzoxazinyl, dihydro-1,3-benzoxazinyl,
dihydro-1,4-benzoxazinyl, 1,2- and 3,4-dihydroquinolinyl,
1,2,3,4-tetrahydroquinolinyl, 1,2- and 3,4-dihydroisoquinolinyl,
1,2,3,4-tetrahydroisoquinolinyl, 1,2- and 3,4-dihydroquinoxalinyl,
1,2,3,4-tetrahydroquinoxalinyl, 1,2- and 3,4-dihydroquinazolinyl,
1,2,3,4-tetrahydroquinazolinyl, 1,2- and 3,4-dihydrocinnolinyl,
1,2,3,4-tetahydrocinnolinyl, chromenyl, chromonyl, isochromenyl,
chromanyl, chromanonyl and isochromanyl, more particularly from
indanyl, such as indan-1-yl, indenyl, such as inden-3-yl,
indanonyl, such as indan-2-on-1-yl or indan-3-on-1-yl, tetralinyl,
such as tetralin-1-yl, dihydronaphthyl, such as
1,2-dihydronaphth-1-yl or 1,4-dihydronaphth-1-yl,
2,3-dihydrobenzofuranyl, benzo-1,3-dioxyl, benzo-1,4-dioxanyl,
chromenyl, chromonyl, isochromenyl, chromanyl, chromanonyl and
isochromanyl, and specifically from indanyl, such as indan-1-yl,
and isochromanyl, such as isochroman-4-yl.
[0165] For these radicals, R.sup.15 is preferably selected from
hydroxyl, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl,
C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-haloalkoxy, more
preferably from hydroxyl, C.sub.1-C.sub.4-alkoxy or
C.sub.1-C.sub.4-haloalkoxy and specifically is hydroxyl.
[0166] Particularly preferred compounds I are those of formulae
I.1.ab to I.58.ab and the racemates thereof where the variables
have the above or, preferably, the below given meanings.
##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008##
##STR00009## ##STR00010## ##STR00011## ##STR00012## ##STR00013##
##STR00014## ##STR00015## ##STR00016## ##STR00017## ##STR00018##
##STR00019## ##STR00020## ##STR00021##
[0167] Examples of particularly preferred compounds of the general
formula I are the compounds I compiled in Tables 1 to 3583094below.
Moreover, the meanings mentioned for the individual variables in
the tables are per se, independently of the combination in which
they are mentioned, a particularly preferred embodiment of the
substituents in question.
Table 1
[0168] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is H and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 2
[0169] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is OH and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 3
[0170] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is OCH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 4
[0171] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is OCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 5
[0172] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is phenyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 6
[0173] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NH.sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 7
[0174] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 8
[0175] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 9
[0176] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH.sub.2CH.sub.2CH.sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 10
[0177] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH(CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 11
[0178] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 12
[0179] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH.sub.2CH(CH.sub.3).sub.2 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 13
[0180] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHCH(CH.sub.3)CH.sub.2CH.sub.3
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 14
[0181] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(CH.sub.3).sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 15
[0182] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is N(CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 16
[0183] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is N(CH.sub.2CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 17
[0184] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is N(CH.sub.2CH.sub.2CH.sub.3).sub.2
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 18
[0185] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OCH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 19
[0186] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 20
[0187] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OCH.sub.2CH.sub.2CH.sub.3
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 21
[0188] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OCH(CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 22
[0189] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHC(O)OCH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 23
[0190] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OCH.sub.2CH(CH.sub.3).sub.2
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 24
[0191] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHC(O)OCH(CH.sub.3)CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 25
[0192] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)OC(CH.sub.3).sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 26
[0193] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)O-phenyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 27
[0194] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHC(O)O-4-tolyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 28
[0195] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 29
[0196] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2CH.sub.2CH.sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 30
[0197] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHSO.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 31
[0198] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2CH(CH.sub.3).sub.2 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 32
[0199] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHSO.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 33
[0200] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHSO.sub.2CH.sub.2CH(CH.sub.3).sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 34
[0201] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is
NHSO.sub.2CH(CH.sub.3)CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 35
[0202] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2C(CH.sub.3).sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 36
[0203] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2-phenyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 37
[0204] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is NHSO.sub.2-4-tolyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 38
[0205] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-azetidinyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 39
[0206] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-pyrrolidinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 40
[0207] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-piperidinyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 41
[0208] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-piperazinyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 42
[0209] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 4-methylpiperazin-1-yl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 43
[0210] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 4-morpholinyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 44
[0211] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 4-thiomorpholinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 45
[0212] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-pyrrolyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 46
[0213] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-pyrazolyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 47
[0214] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH.sub.2, Z is 1-imidazolyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 48
[0215] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CHOH, Z is H and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 49
[0216] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CHOH, Z is phenyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 50
[0217] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is H and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 51
[0218] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is OH and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 52
[0219] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is OCH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 53
[0220] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is OCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 54
[0221] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is phenyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 55
[0222] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NH.sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 56
[0223] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 57
[0224] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 58
[0225] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH.sub.2CH.sub.2CH.sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 59
[0226] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH(CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 60
[0227] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 61
[0228] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH.sub.2CH(CH.sub.3).sub.2
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 62
[0229] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHCH(CH.sub.3)CH.sub.2CH.sub.3
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 63
[0230] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(CH.sub.3).sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 64
[0231] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is N(CH.sub.3).sub.2 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 65
[0232] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is N(CH.sub.2CH.sub.3).sub.2 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 66
[0233] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
N(CH.sub.2CH.sub.2CH.sub.3).sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 67
[0234] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)OCH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 68
[0235] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)OCH.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 69
[0236] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)OCH.sub.2CH.sub.2CH.sub.3
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 70
[0237] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)OCH(CH.sub.3).sub.2 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 71
[0238] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHC(O)OCH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 72
[0239] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHC(O)OCH.sub.2CH(CH.sub.3).sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 73
[0240] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHC(O)OCH(CH.sub.3)CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 74
[0241] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)OC(CH.sub.3).sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 75
[0242] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)O-phenyl and the
combination (R.sup.10), for a compound corresponds in each case to
one row of Table A.
Table 76
[0243] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHC(O)O-4-tolyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 77
[0244] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2CH.sub.3 and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 78
[0245] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2CH.sub.2CH.sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 79
[0246] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHSO.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 80
[0247] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2CH(CH.sub.3).sub.2
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table A.
Table 81
[0248] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHSO.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 82
[0249] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHSO.sub.2CH.sub.2CH(CH.sub.3).sub.2 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 83
[0250] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is
NHSO.sub.2CH(CH.sub.3)CH.sub.2CH.sub.3 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 84
[0251] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2C(CH.sub.3).sub.3 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 85
[0252] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2-phenyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 86
[0253] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is NHSO.sub.2-4-tolyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 87
[0254] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-azetidinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 88
[0255] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-pyrrolidinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 89
[0256] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-piperidinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 90
[0257] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-piperazinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 91
[0258] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 4-methylpiperazin-1-yl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 92
[0259] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 4-morpholinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 93
[0260] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 4-thiomorpholinyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 94
[0261] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-pyrrolyl and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table A.
Table 95
[0262] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-pyrazolyl and the
combination)(R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Table 96
[0263] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which R.sup.1 is H, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H,
R.sup.6 is H, Y is CH(phenyl), Z is 1-imidazolyl and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Tables 97 to 192
[0264] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
H.
Tables 193 to 288
[0265] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
CH.sub.3.
Tables 289 to 384
[0266] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is F.
Tables 385 to 480
[0267] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
CH.sub.3.
Tables 481 to 576
[0268] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
F.
Tables 577 to 672
[0269] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
OCH.sub.3.
Tables 673 to 768
[0270] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
OCH.sub.3.
Tables 769 to 864
[0271] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 865 to 960
[0272] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
H.
Tables 961 to 1056
[0273] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and
R.sup.6 is H.
Tables 1057 to 1152
[0274] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
CH.sub.3.
Tables 1153 to 1248
[0275] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
F.
Tables 1249 to 1344
[0276] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and
R.sup.6 is CH.sub.3.
Tables 1345 to 1440
[0277] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and
R.sup.6 is F.
Tables 1441 to 1536
[0278] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
OCH.sub.3.
Tables 1537 to 1632
[0279] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and
R.sup.6 is OCH.sub.3.
Tables 1633 to 1728
[0280] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 1729 to 1824
[0281] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is H.
Tables 1825 to 1920
[0282] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
H.
Tables 1921 to 2016
[0283] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
CH.sub.3.
Tables 2017 to 2112
[0284] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is F.
Tables 2113 to 2208
[0285] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
CH.sub.3.
Tables 2209 to 2304
[0286] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
F.
Tables 2305 to 2400
[0287] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
OCH.sub.3.
Tables 2401 to 2496
[0288] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
OCH.sub.3.
Tables 2497 to 2592
[0289] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 2593 to 2688
[0290] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is H.
Tables 2689 to 2784
[0291] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
H.
Tables 2785 to 2880
[0292] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
CH.sub.3.
Tables 2881 to 2977
[0293] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is F.
Tables 2978 to 3072
[0294] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
CH.sub.3.
Tables 3073 to 3168
[0295] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
F.
Tables 3169 to 3264
[0296] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
OCH.sub.3.
Tables 3265 to 3360
[0297] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
OCH.sub.3.
Tables 3361 to 3456
[0298] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 3457 to 3552
[0299] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is H.
Tables 3553 to 3648
[0300] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is H.
Tables 3649 to 3744
[0301] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is CH.sub.3.
Tables 3745 to 3840
[0302] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is F.
Tables 3841 to 3936
[0303] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is CH.sub.3.
Tables 3937 to 4032
[0304] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is F.
Tables 4033 to 4128
[0305] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is OCH.sub.3.
Tables 4129 to 4224
[0306] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is OCH.sub.3.
Tables 4225 to 4320
[0307] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is F and
R.sup.6 is OCH.sub.3.
Tables 4321 to 4416
[0308] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
H.
Tables 4417 to 4512
[0309] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
CH.sub.3.
Tables 4513 to 4608
[0310] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
F.
Tables 4609 to 4704
[0311] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
OCH.sub.3.
Tables 4705 to 4800
[0312] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 4801 to 4896
[0313] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
CH.sub.3.
Tables 4897 to 4992
[0314] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is F.
Tables 4993 to 5088
[0315] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
CH.sub.3.
Tables 5089 to 5184
[0316] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
F.
Tables 5185 to 5280
[0317] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
OCH.sub.3.
Tables 5281 to 5376
[0318] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
OCH.sub.3.
Tables 5377 to 5472
[0319] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is
OCH.sub.3.
Tables 5473 to 5568
[0320] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and
R.sup.5 is H.
Tables 5569 to 5664
[0321] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
CH.sub.3.
Tables 5665 to 5760
[0322] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
F.
Tables 5761 to 5856
[0323] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and
R.sup.5 is CH.sub.3.
Tables 5857 to 5952
[0324] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and
R.sup.5 is F.
Tables 5953 to 6048
[0325] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
OCH.sub.3.
Tables 6049 to 6144
[0326] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and
R.sup.5 is OCH.sub.3.
Tables 6145 to 6240
[0327] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is
OCH.sub.3.
Tables 6241 to 6336
[0328] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
CH.sub.3.
Tables 6337 to 6432
[0329] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is F.
Tables 6433 to 6528
[0330] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
CH.sub.3.
Tables 6529 to 6624
[0331] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
F.
Tables 6625 to 6720
[0332] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
OCH.sub.3.
Tables 6721 to 6816
[0333] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
OCH.sub.3.
Tables 6817 to 6912
[0334] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
OCH.sub.3.
Tables 6913 to 7008
[0335] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
H.
Tables 7009 to 7104
[0336] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.15).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
CH.sub.3.
Tables 7105 to 7200
[0337] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is F.
Tables 7201 to 7296
[0338] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
CH.sub.3.
Tables 7297 to 7392
[0339] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
F.
Tables 7393 to 7488
[0340] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
OCH.sub.3.
Tables 7489 to 7584
[0341] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.15).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
OCH.sub.3.
Tables 7585 to 7680
[0342] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is
OCH.sub.3.
Tables 7681 to 7776
[0343] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is H and
R.sup.5 is H.
Tables 7777 to 7872
[0344] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is H and
R.sup.5 is CH.sub.3.
Tables 7873 to 7968
[0345] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is H and
R.sup.5 is F.
Tables 7969 to 8064
[0346] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is CH.sub.3.
Tables 8065 to 8160
[0347] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is CH.sub.3
and R.sup.5 is F.
Tables 8161 to 8256
[0348] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is OCH.sub.3.
Tables 8257 to 8352
[0349] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is CH.sub.3
and R.sup.5 is OCH.sub.3.
Tables 8353 to 8448
[0350] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is F and
R.sup.5 is OCH.sub.3.
Tables 8449 to 8544
[0351] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
CH.sub.3.
Tables 8545 to 8640
[0352] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
F.
Tables 8641 to 8736
[0353] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
OCH.sub.3.
Tables 8737 to 8832
[0354] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.6 is H, R.sup.3 is F and R.sup.5 is
OCH.sub.3.
Tables 8833 to 8928
[0355] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is Cl.
Tables 8929 to 9025
[0356] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is
Cl.
Tables 9025 to 9120
[0357] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is Cl.
Tables 9121 to 9216
[0358] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is H and R.sup.5 is Cl.
Tables 9217 to 9312
[0359] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is H and
R.sup.5 is Cl.
Tables 9313 to 9408
[0360] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 9409 to 9504
[0361] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and
R.sup.5 is Cl.
Tables 9505 to 9600
[0362] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 9601 to 9696
[0363] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 9697 to 9792
[0364] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is CH.sub.3
and R.sup.5 is Cl.
Tables 9793 to 9888
[0365] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is Cl.
Tables 9889 to 9984
[0366] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is
Cl.
Tables 9985 to 10080
[0367] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is Cl.
Tables 10081 to 10176
[0368] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is Cl.
Tables 10177 to 10272
[0369] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.6 is H, R.sup.3 is F and
R.sup.5 is Cl.
Tables 10273 to 10368
[0370] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 10369 to 10464
[0371] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is Cl.
Tables 10465 to 10560
[0372] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is
Cl.
Tables 10561 to 10656
[0373] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is Cl.
Tables 10657 to 10752
[0374] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is H and R.sup.6 is Cl.
Tables 10753 to 10848
[0375] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is H and
R.sup.6 is Cl.
Tables 10849 to 10944
[0376] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
Cl.
Tables 10945 to 11040
[0377] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and
R.sup.6 is Cl.
Tables 11041 to 11136
[0378] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 11137 to 11232
[0379] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is CH.sub.3 and R.sup.6 is
Cl.
Tables 11233 to 11328
[0380] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is CH.sub.3
and R.sup.6 is Cl.
Tables 11329 to 11424
[0381] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is Cl.
Tables 11425 to 11520
[0382] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is
Cl.
Tables 11521 to 11616
[0383] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is F,
R.sup.2 is H, R.sup.6 is H, R.sup.3 is F and R.sup.5 is Cl.
Tables 11617 to 11712
[0384] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is Cl,
R.sup.2 is H, R.sup.5 is H, R.sup.3 is F and R.sup.6 is Cl.
Tables 11713 to 11808
[0385] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is
CH.sub.3, R.sup.2 is CH.sub.3, R.sup.5 is H, R.sup.3 is F and
R.sup.6 is Cl.
Tables 11809 to 11904
[0386] Compounds of the formula I.1.a, I.1.b and mixtures thereof,
in which the combination of Y and Z is as defined in one of Tables
1 to 96, the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table A, R.sup.1 is H,
R.sup.2 is F, R.sup.6 is H, R.sup.3 is CH.sub.3 and R.sup.5 is
Cl.
Tables 11905 to 23808
[0387] Compounds of the formula I.2.a, I.2.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table A.
Tables 23809 to 35712
[0388] Compounds of the formula I.3.a, I.3.b and mixtures thereof,
in which the combination of Y, Z, R.sup.3 and R.sup.6 is as defined
in one of Tables 1 to 576 and the combination (R.sup.10).sub.n for
a compound corresponds in each case to one row of Table A.
Tables 35713 to 47616
[0389] Compounds of the formula I.4.a, I.4.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table B (B.a).
Tables 47618 to 59520
[0390] Compounds of the formula I.5.a, I.5.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table B (B.b).
Tables 59521 to 71424
[0391] Compounds of the formula I.6.a, I.6.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table B (B.c).
Tables 71425 to 83328
[0392] Compounds of the formula I.7.a, I.7.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table C(C.a).
Tables 83329 to 95232
[0393] Compounds of the formula I.8.a, I.8.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table C(C.b).
Tables 95233 to 107136
[0394] Compounds of the formula I.9.a, I.9.b and mixtures thereof,
in which the combination of Y, Z, R.sup.1, R.sup.2, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904 and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table C(C.a).
Tables 107137 to 119040
[0395] Compounds of the formula I.10.a, I.10.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904 and the combination (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 119041 to 130944
[0396] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and the combination (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C (C.a).
Tables 130945 to 142848
[0397] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 142849 to 154752
[0398] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 154753 to 166656
[0399] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904,
R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 166657 to 178560
[0400] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C (C.a).
Tables 178561 to 190464
[0401] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 190465 to 202368
[0402] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table
C(C.a).
Tables 202369 to 214272
[0403] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C(C.a).
Tables 214273 to 226176
[0404] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 226177 to 238080
[0405] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is --C(O)--O--C(CH.sub.3).sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C (C.a).
Tables 238081 to 249984
[0406] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 249985 to 261888
[0407] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 261889 to 273792
[0408] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 273793 to 285696
[0409] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 285697 to 297600
[0410] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is 2-methoxyphenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table C(C.a).
Tables 297601 to 309504
[0411] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 309505 to 321408
[0412] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.a).
Tables 321409 to 333312
[0413] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 333313 to 345216
[0414] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 345217 to 357120
[0415] Compounds of the formula I.11.a, I.11.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.a).
Tables 357121 to 369024
[0416] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and the combination (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C (C.b).
Tables 369025 to 380928
[0417] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is CH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C(C.b).
Tables 380929 to 392832
[0418] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 392833 to 404736
[0419] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table
C(C.b).
Tables 404737 to 416640
[0420] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C (C.b).
Tables 416641 to 428544
[0421] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 428545 to 440448
[0422] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table
C(C.b).
Tables 440449 to 452352
[0423] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C(C.b).
Tables 452353 to 464256
[0424] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 464257 to 476160
[0425] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 476161 to 488064
[0426] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 488065 to 499968
[0427] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 499969 to 511872
[0428] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 511873 to 523776
[0429] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 523777 to 535680
[0430] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is 2-methoxyphenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table C(C.b).
Tables 535681 to 547584
[0431] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 547585 to 559488
[0432] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table C(C.b).
Tables 559489 to 571392
[0433] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C(C.b).
Tables 571393 to 583296
[0434] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 583297 to 595200
[0435] Compounds of the formula I.12.a, I.12.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C(C.b).
Tables 595201 to 607104
[0436] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 288607105 01 to 619008
[0437] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 619009 to 630912
[0438] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 630913 to 642816
[0439] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904 6, R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.a).
Tables 642817 to 654720
[0440] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 654721 to 666624
[0441] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 666625 to 678528
[0442] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.a).
Tables 678529 to 690432
[0443] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.a).
Tables 690433 to 702336
[0444] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 702337 to 714240
[0445] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is --C(O)--O--C(CH.sub.3).sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.a).
Tables 714241 to 726144
[0446] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 726145 to 738048
[0447] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 738049 to 749952
[0448] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 749953 to 761856
[0449] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 761857 to 773760
[0450] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 773761 to 785664
[0451] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 785665 to 797568
[0452] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.a).
Tables 797569 to 809472
[0453] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 809473 to 821376
[0454] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 821377 to 833280
[0455] Compounds of the formula I.13.a, I.13.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.a).
Tables 833281 to 845184
[0456] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 845185 to 857088
[0457] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 857089 to 868992
[0458] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 868993 to 880896
[0459] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.b).
Tables 880897 to 892800
[0460] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table D (D.b).
Tables 892801 to 904704
[0461] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 904705 to 916608
[0462] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.b).
Tables 916609 to 928512
[0463] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.b).
Tables 928513 to 940416
[0464] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 940417 to 952320
[0465] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is --C(O)--O--C(CH.sub.3).sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.b).
Tables 952321 to 964224
[0466] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 964225 to 976128
[0467] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 976129 to 988032
[0468] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 988033 to 99936
[0469] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 99937 to 1011840
[0470] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 1011841 to 1023744
[0471] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 1023745 to 1035648
[0472] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.b).
Tables 1035649 to 1047552
[0473] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 1047553 to 1059456
[0474] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 1059457 to 1071360
[0475] Compounds of the formula I.14.a, I.14.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.b).
Tables 1071361 to 1083264
[0476] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1083265 to 1095168
[0477] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c)
Tables 1095169 to 1107072
[0478] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576 R.sup.101 is CH.sub.2CH.sub.3
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table D (D.c).
Tables 1107073 to 1118976
[0479] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.c).
Tables 1118977 to 1130880
[0480] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1130881 to 1142784
[0481] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1142785 to 1154688
[0482] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table D
(D.c).
Tables 1154689 to 1166592
[0483] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10) for a compound corresponds in each case to one row of
Table D (D.c).
Tables 1166593 to 1178496
[0484] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1178497 to 1190400
[0485] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is --C(O)--O--C(CH.sub.3).sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.c).
Tables 1190401 to 1202304
[0486] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.3 and R.sup.6 is
as defined in one of Tables 1 to 576, R.sup.101 is phenyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.c).
Tables 1202305 to 1214208
[0487] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1214209 to 1226112
[0488] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1226113 to 1238016
[0489] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1238017 to 1249920
[0490] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1249921 to 1261824
[0491] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, .sup.R101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1261825 to 1273728
[0492] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2, K
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, .sup.R101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table D (D.c).
Tables 1273729 to 1285632
[0493] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1285633 to 1297536
[0494] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1297537 to 1309440
[0495] Compounds of the formula I.15.a, I.15.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-pyridyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table D (D.c).
Tables 1309441 to 1321344
[0496] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is H and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1321345 to 1333248
[0497] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1333249 to 1345152
[0498] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904 R.sup.101 is CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table E (E.a).
Tables 1345153 to 1357056
[0499] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table E
(E.a).
Tables 1357057 to 1368960
[0500] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table E (E.a).
Tables 1368961 to 1380864
[0501] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CHF.sub.2 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1380865 to 1392768
[0502] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n
for a compound corresponds in each case to one row of Table E
(E.a).
Tables 1392769 to 1404672
[0503] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and
(R.sup.10) for a compound corresponds in each case to one row of
Table E (E.a).
Tables 1404673 to 1416576
[0504] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is cyclohexyl and (R.sup.10) for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1416577 to 1428480
[0505] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is --C(O)--O--C(CH.sub.3).sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1428481 to 1440384
[0506] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1440385 to 1452288
[0507] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table E (E.a).
Tables 1452289 to 1464192
[0508] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.3,
R.sup.5 and R.sup.6 is as defined in one of Tables 1 to 11904,
R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.a).
Tables 1464193 to 1476096
[0509] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table E (E.a).
Tables 1476097 to 1488000
[0510] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.a).
Tables 1488001 to 1499904
[0511] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.a).
Tables 1499905 to 1511808
[0512] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.a).
Tables 1511809 to 1523712
[0513] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1523713 to 1535616
[0514] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1535617 to 1547520
[0515] Compounds of the formula I.16.a, I.16.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1547521 to 1559424
[0516] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is H and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 15594245 to 1571328
[0517] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1571329 to 1583232
[0518] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.b).
Tables 1583233 to 1595136
[0519] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.b).
Tables 1595137 to 1607040
[0520] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table E (E.b).
Tables 1607041 to 1618944
[0521] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table C.
Tables 1618945 to 1630848
[0522] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.b).
Tables 1630849 to 1642752
[0523] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table E (E.b)
Tables 1642753 to 1654656
[0524] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1654657 to 1666560
[0525] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table E (E.b).
Tables 1666561 to 1678464
[0526] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is phenyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1678465 to 1690368
[0527] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table E (E.b).
Tables 1690369 to 1702272
[0528] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table E (E.b).
Tables 17022723 to 1714176
[0529] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table E (E.b).
Tables 1714177 to 1726080
[0530] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.b).
Tables 1726081 to 1737984
[0531] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.b).
Tables 1737985 to 1749888
[0532] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table E (E.b).
Tables 1749889 to 1761792
[0533] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1761793 to 1773696
[0534] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1773697 to 1785600
[0535] Compounds of the formula I.17.a, I.17.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b)C.
Tables 1785601 to 1797504
[0536] Compounds of the formula I.18.a, I.18.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1797505 to 1809408
[0537] Compounds of the formula I.19.a, I.19.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1809409 to 1821312
[0538] Compounds of the formula I.20.a, I.20.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.c).
Tables 1821313 1833216
[0539] Compounds of the formula I.21.a, I.21.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.a).
Tables 1833217 to 1845120
[0540] Compounds of the formula I.22.a, I.22.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.b).
Tables 1845121 to 1857024
[0541] Compounds of the formula I.23.a, I.23.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table E (E.c).
Tables 1857025 to 1868928
[0542] Compounds of the formula I.24.a, I.24.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.a).
Tables 1868929 to 1880832
[0543] Compounds of the formula I.25.a, I.25.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.b).
Tables 1868923 to 1892736
[0544] Compounds of the formula I.26.a, I.26.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.a).
Tables 1892737 to 1904640
[0545] Compounds of the formula I.27.a, I.27.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table D (D.b).
Tables 1904641 to 1916544
[0546] Compounds of the formula I.28.a, I.28.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.10 for a compound
corresponds in each case to one row of Table F.
Tables 1916545 to 1928448
[0547] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is H and R.sup.10
for a compound corresponds in each case to one row of Table F.
Tables 1928449 to 1940352
[0548] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and R.sup.10 for a compound
corresponds in each case to one row of Table F.
Tables 1940353 to 1952256
[0549] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and R.sup.10 for a compound corresponds in each
case to one row of Table F.
Tables 1952257 to 1964160
[0550] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and R.sup.10 for a compound corresponds in
each case to one row of Table F.
Tables 1964161 to 1976064
[0551] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and R.sup.10 for a compound corresponds in each
case to one row of Table F.
Tables 1976065 to 1987968
[0552] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 1987969 to 199872
[0553] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and R.sup.10 for a compound corresponds
in each case to one row of Table F.
Tables 199873 to 2011776
[0554] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and R.sup.10 for a compound
corresponds in each case to one row of Table F.
Tables 2011777 to 2023680
[0555] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2023681 to 2035584
[0556] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and R.sup.10 for a compound
corresponds in each case to one row of Table F.
Tables 2035585 to 2047488
[0557] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is phenyl and
R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2047489 to 2059392
[0558] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-fluorophenyl
and R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2059393 to 2071296
[0559] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-fluorophenyl
and R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2071297 to 2083200
[0560] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2083201 to 2095104
[0561] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and R.sup.10 for a compound corresponds in each
case to one row of Table F.
Tables 2095105 to 2107008
[0562] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and R.sup.10 for a compound corresponds in each
case to one row of Table F.
Tables 2107009 to 2118912
[0563] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and R.sup.10 for a compound corresponds in each
case to one row of Table F.
Tables 2118913 to 2130816
[0564] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table F.
Tables 2130817 to 2142720
[0565] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2142721 to 2154624
[0566] Compounds of the formula I.29.a, I.29.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
R.sup.10 for a compound corresponds in each case to one row of
Table F.
Tables 2154625 to 2166528
[0567] Compounds of the formula I.30.a, I.30.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 2166529 to 2178432
[0568] Compounds of the formula I.31.a, I.31.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2178431 to 2190336
[0569] Compounds of the formula I.32.a, I.32.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2190337 to 2202240
[0570] Compounds of the formula I.33.a, I.33.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2202241 to 2214144
[0571] Compounds of the formula I.34.a, I.34.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2214145 to 2226048
[0572] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is H and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2226049 to 2237952
[0573] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2237953 to 2249856
[0574] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2249857 to 2261760
[0575] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2261761 to 2273664
[0576] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 2273665 to 2285568
[0577] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2285569 to 2297472
[0578] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2297473 to 2309376
[0579] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2309377 to 2321280
[0580] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2321281 to 2333184
[0581] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2333185 to 2345088
[0582] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is phenyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2345089 to 2356992
[0583] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 2356993 to 2368896
[0584] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2368897 to 2380800
[0585] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2380801 to 2392704
[0586] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2392705 to 2404608
[0587] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 3-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2404609 to 2416512
[0588] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 4-methoxyphenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2416513 to 2428416
[0589] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2428417 to 2440320
[0590] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2440321 to 2452224
[0591] Compounds of the formula I.35.a, I.35.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2452225 to 2464128
[0592] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination of
R.sup.101 is H and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2464129 to 2476032
[0593] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2476033 to 2487936
[0594] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2487937 to 2499840
[0595] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2499841 to 2511744
[0596] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 2511745 to 2523648
[0597] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2523649 to 2535552
[0598] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2535553 to 2547456
[0599] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10) for a compound
corresponds in each case to one row of Table G.
Tables 2547457 to 2559360
[0600] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2559361 to 2571264
[0601] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables
[0602] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is phenyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2571265 to 2583168
[0603] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 2583169 to 2595072
[0604] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 2595073 to 260976
[0605] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 260977 to 2618880
[0606] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2618881 to 2630784
[0607] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2630785 to 2642688
[0608] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2642689 to 2654592
[0609] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2654593 to 2666496
[0610] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2666497 to 2678400
[0611] Compounds of the formula I.36.a, I.36.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2678401 to 2690304
[0612] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is H and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2690305 to 2702208
[0613] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2702209 to 2714112
[0614] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2714113 to 2726016
[0615] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2726017 to 2737920
[0616] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 2737921 to 2749824
[0617] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2749825 to 2761728
[0618] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2761729 to 2773632
[0619] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2773633 to 2785536
[0620] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2785537 to 2797440
[0621] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table C.
Tables 2797441 to 2809344
[0622] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is phenyl and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2809345 to 2821248
[0623] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R.sup.1, R.sup.2,
R.sup.3, R.sup.5 and R.sup.6 is as defined in one of Tables 1 to
11904, R.sup.101 is 2-fluorophenyl and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 2821249 to 2833152
[0624] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 2833153 to 2845056
[0625] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 2845057 to 2856960
[0626] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2856961 to 2868864
[0627] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2868865 to 2880768
[0628] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2880769 to 2892672
[0629] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2892673 to 2904576
[0630] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2904577 to 2916480
[0631] Compounds of the formula I.37.a, I.37.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2916481 to 2928384
[0632] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is H and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2928385 to 2940288
[0633] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CH.sub.3 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2940289 to 2952192
[0634] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 R.sup.101 is
CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 2952193 to 2964096
[0635] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2964097 to 2976000
[0636] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH(CH.sub.3).sub.2 and (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 2976001 to 2987904
[0637] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is CHF.sub.2 and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 2987905 to 2999808
[0638] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 2999809 to 3011712
[0639] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 and (R.sup.10).sub.n for a
compound corresponds in each case to one row of Table G.
Tables 3011713 to 3023616
[0640] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is cyclohexyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3023617 to 3035520
[0641] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
--C(O)--O--C(CH.sub.3).sub.3 and (R.sup.10).sub.n for a compound
corresponds in each case to one row of Table G.
Tables 3035521 to 3047424
[0642] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is phenyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3047425 to 3059328
[0643] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 3059329 to 3071232
[0644] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 3071233 to 3083136
[0645] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-fluorophenyl
and (R.sup.10).sub.n for a compound corresponds in each case to one
row of Table G.
Tables 3083137 to 3095040
[0646] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
2-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3095041 to 3106944
[0647] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
3-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3106945 to 3118848
[0648] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is
4-methoxyphenyl and (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3118849 to 3130752
[0649] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 2-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3130753 to 3142656
[0650] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 3-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3142657 to 3154560
[0651] Compounds of the formula I.38.a, I.38.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, R.sup.101 is 4-pyridyl and
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3154561 to 3166464
[0652] Compounds of the formula I.39.a, I.39.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3166465 to 3178368
[0653] Compounds of the formula I.40.a, I.40.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3178369 to 3190272
[0654] Compounds of the formula I.41.a, I.41.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table F.
Tables 3190273 to 3202176
[0655] Compounds of the formula I.42.a, I.42.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
Tables 3202177 to 3214080
[0656] Compounds of the formula I.43.a, I.43.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3214081 to 3225984
[0657] Compounds of the formula I.44.a, I.44.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and the combination
(R.sup.10).sub.n for a compound corresponds in each case to one row
of Table G.
Tables 3225985 to 3237888
[0658] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A is O, B, C and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3237889 to 3249792
[0659] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, B is O, A, C and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3249793 to 3261696
[0660] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, C is O, A, B and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3261697 to 3273600
[0661] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, D is O, A, B and C are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3273601 to 3285504
[0662] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and D are O, B and C are
CH and the combination (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 3285505 to 3297408
[0663] Compounds of the formula I.45.a, I.45.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A, B, C and D are CH and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3297409 to 3309312
[0664] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A is O, B, C and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3309313 to 3321216
[0665] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, B is O, A, C and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3321217 to 3333120
[0666] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, C is O, A, B and D are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3333121 to 3345024
[0667] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, D is O, A, B and C are CH
and the combination (R.sup.10).sub.n for a compound corresponds in
each case to one row of Table G.
Tables 3345025 to 3356928
[0668] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and D are O, B and C are
CH and the combination (R.sup.10).sub.n for a compound corresponds
in each case to one row of Table G.
Tables 3356929 to 3368832
[0669] Compounds of the formula I.46.a, I.46.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A, B, C and D are CH and
the combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3368833 to 3380736
[0670] Compounds of the formula I.47.a, I.47.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A is O, B is CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3380737 to 3392640
[0671] Compounds of the formula I.47.a, I.47.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, B is O, A is CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3392641 to 3404544
[0672] Compounds of the formula I.47.a, I.47.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and B are CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3404545 to 3416448
[0673] Compounds of the formula I.47.a, I.47.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and B are O and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3416449 to 3428352
[0674] Compounds of the formula I.48.a, I.48.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A is O, B is CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3428353 to 3440256
[0675] Compounds of the formula I.48.a, I.48.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, B is O, A is CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3440257 to 3452160
[0676] Compounds of the formula I.48.a, I.48.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and B are CH and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3452161 to 3464064
[0677] Compounds of the formula I.48.a, I.48.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904, A and B are O and the
combination (R.sup.10).sub.n for a compound corresponds in each
case to one row of Table G.
Tables 3464065 to 3475968
[0678] Compounds of the formula I.49.a, I.49.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 3475969 to 3487872
[0679] Compounds of the formula I.50.a, I.50.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 3487873 to 3499776
[0680] Compounds of the formula I.51.a, I.51.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 3499777 to 3511680
[0681] Compounds of the formula I.52.a, I.52.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 3511681 to 3523584
[0682] Compounds of the formula I.53.a, I.53.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904 and R.sup.101 for a compound
corresponds in each case to one row of Table H.
Tables 3523585 to 3535488
[0683] Compounds of the formula I.54.a, I.54.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
Tables 3535489 to 3547392
[0684] Compounds of the formula I.55.a, I.55.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
Tables 3547393 to 3559286
[0685] Compounds of the formula I.56.a, I.56.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
Tables 3559287 to 3571190
[0686] Compounds of the formula I.57.a, I.57.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
Tables 3571191 to 3583094
[0687] Compounds of the formula I.58.a, I.58.b and mixtures
thereof, in which the combination of Y, Z, R1, R2, R3, R5 and R6 is
as defined in one of Tables 1 to 11904.
TABLE-US-00001 TABLE A ##STR00022## No. (R.sup.10).sub.n A-1. --
A-2. 2-F A-3. 3-F A-4. 4-F A-5. 2,3-F.sub.2 A-6. 2,4-F.sub.2 A-7.
2,5-F.sub.2 A-8. 2,6-F.sub.2 A-9. 3,4-F.sub.2 A-10. 3,5-F.sub.2
A-11. 2,3,4-F.sub.3 A-12. 2,3,5-F.sub.3 A-13. 2,3,6-F.sub.3 A-14.
2,4,5-F.sub.3 A-15. 2,4,6-F.sub.3 A-16. 3,4,5-F.sub.3 A-17.
2,3,4,5-F.sub.4 A-18. 2,3,4,6-F.sub.4 A-19. 2,3,5,6-F.sub.4 A-20.
2,3,4,5,6-F.sub.5 A-21. 2-Cl A-22. 3-Cl A-23. 4-Cl A-24.
2,3-Cl.sub.2 A-25. 2,4-Cl.sub.2 A-26. 2,5-Cl.sub.2 A-27.
2,6-Cl.sub.2 A-28. 3,4-Cl.sub.2 A-29. 3,5-Cl.sub.2 A-30.
2,3,4-Cl.sub.3 A-31. 2,3,5-Cl.sub.3 A-32. 2,3,6-Cl.sub.3 A-33.
2,4,5-Cl.sub.3 A-34. 2,4,6-Cl.sub.3 A-35. 3,4,5-Cl.sub.3 A-36.
2,3,4,5-Cl.sub.4 A-37. 2,3,4,6-Cl.sub.4 A-38. 2,3,5,6-Cl.sub.4
A-39. 2,3,4,5,6-Cl.sub.5 A-40. 2-Br A-41. 3-Br A-42. 4-Br A-43.
2,3-Br.sub.2 A-44. 2,4-Br.sub.2 A-45. 2,5-Br.sub.2 A-46.
2,6-Br.sub.2 A-47. 3,4-Br.sub.2 A-48. 3,5-Br.sub.2 A-49.
2,3,4-Br.sub.3 A-50. 2,3,5-Br.sub.3 A-51. 2,3,6-Br.sub.3 A-52.
2,4,5-Br.sub.3 A-53. 2,4,6-Br.sub.3 A-54. 3,4,5-Br.sub.3 A-55.
2,3,4,5-Br.sub.4 A-56. 2,3,4,6-Br.sub.4 A-57. 2,3,5,6-Br.sub.4
A-58. 2,3,4,5,6-Br.sub.5 A-59. 2-I A-60. 3-I A-61. 4-I A-62. 2-F,
3-Cl A-63. 2-F, 4-Cl A-64. 2-F, 5-Cl A-65. 2-F, 6-Cl A-66. 3-F,
4-Cl A-67. 3-F, 5-Cl A-68. 3-F, 6-Cl A-69. 2-Cl, 3-F A-70. 2-Cl,
4-F A-71. 3-Cl, 4-F A-72. 5-Cl, 4-F A-73. 2,3-F.sub.2, 4-Cl A-74.
2,3-F.sub.2, 5-Cl A-75. 2,3-F.sub.2, 6-Cl A-76. 2,4-F.sub.2, 3-Cl
A-77. 2,4-F.sub.2, 5-Cl A-78. 2,4-F.sub.2, 6-Cl A-79. 2,5-F.sub.2,
3-Cl A-80. 2,5-F.sub.2, 4-Cl A-81. 2,5-F.sub.2, 6-Cl A-82.
3,4-F.sub.2, 5-Cl A-83. 3,4-F.sub.2, 2-Cl A-84. 2,6-F.sub.2, 3-Cl
A-85. 2,6-F.sub.2, 4-Cl A-86. 3,5-F.sub.2, 4-Cl A-87. 2,3-Cl.sub.2,
4-F A-88. 2,3-Cl.sub.2, 5-F A-89. 2,3-Cl.sub.2, 6-F A-90.
2,4-Cl.sub.2, 3-F A-91. 2,4-Cl.sub.2, 5-F A-92. 2,4-Cl.sub.2, 6-F
A-93. 2,5-Cl.sub.2, 3-F A-94. 2,5-Cl.sub.2, 4-F A-95. 2,5-Cl.sub.2,
6-F A-96. 3,4-Cl.sub.2, 5-F A-97. 3,4-Cl.sub.2, 2-F A-98.
2,6-Cl.sub.2, 3-F A-99. 2,6-Cl.sub.2, 4-F A-100. 3,5-Cl.sub.2, 4-F
A-101. 2,3,4-F.sub.3, 5-Cl A-102. 2,3,4-F.sub.3, 6-Cl A-103.
2,3,5-F.sub.3, 6-Cl A-104. 2,3,5-F.sub.3, 4-Cl A-105.
2,3,6-F.sub.3, 4-Cl A-106. 2,3,6-F.sub.3, 5-Cl A-107.
2,4,5-F.sub.3, 3-Cl A-108. 2,4,6-F.sub.3, 3-Cl A-109.
3,5,6-F.sub.3, 2-Cl A-110. 2-F, 3-Br A-111. 2-F, 4-Br A-112. 2-F,
5-Br A-113. 2-F, 6-Br A-114. 3-F, 4-Br A-115. 3-F, 5-Br A-116. 3-F,
6-Br A-117. 2-Br, 3-F A-118. 2-Br, 4-F A-119. 3-Br, 4-F A-120.
5-Br, 4-F A-121. 2,3-F.sub.2, 4-Br A-122. 2,3-F.sub.2, 5-Br A-123.
2,3-F.sub.2, 6-Br A-124. 2,4-F.sub.2, 3-Br A-125. 2,4-F.sub.2, 5-Br
A-126. 2,4-F.sub.2, 6-Br A-127. 2,5-F.sub.2, 3-Br A-128.
2,5-F.sub.2, 4-Br A-129. 2,5-F.sub.2, 6-Br A-130. 3,4-F.sub.2, 5-Br
A-131. 3,4-F.sub.2, 2-Br A-132. 2,6-F.sub.2, 3-Br A-133.
2,6-F.sub.2, 4-Br A-134. 3,5-F.sub.2, 4-Br A-135. 2,3,4-F.sub.3,
5-Br A-136. 2,3,4-F.sub.3, 6-Br A-137. 2,3,5-F.sub.3, 6-Br A-138.
2,3,5-F.sub.3, 4-Br A-139. 2,3,6-F.sub.3, 4-Br A-140.
2,3,6-F.sub.3, 5-Br A-141. 2,4,5-F.sub.3, 3-Br A-142.
2,4,6-F.sub.3, 3-Br A-143. 3,5,6-F.sub.3, 2-Br A-144. 2-F, 3-I
A-145. 2-F, 4-I A-146. 2-F, 5-I A-147. 2-F, 6-I A-148. 3-F, 4-I
A-149. 3-F, 5-I A-150. 3-F, 6-I A-151. 2-I, 3-F A-152. 2-I, 4-F
A-153. 3-I, 4-F A-154. 5-I, 4-F A-155. 2-CH.sub.3 A-156. 3-CH.sub.3
A-157. 4-CH.sub.3 A-158. 2,3-(CH.sub.3).sub.2 A-159.
2,4-(CH.sub.3).sub.2 A-160. 2,5-(CH.sub.3).sub.2 A-161.
2,6-(CH.sub.3).sub.2 A-162. 3,4-(CH.sub.3).sub.2 A-163.
3,5-(CH.sub.3).sub.2 A-164. 2,3,4-(CH.sub.3).sub.3 A-165.
2,3,5-(CH.sub.3).sub.3 A-166. 2,3,6-(CH.sub.3).sub.3 A-167.
2,4,5-(CH.sub.3).sub.3 A-168. 2,4,6-(CH.sub.3).sub.3 A-169.
3,4,5-(CH.sub.3).sub.3 A-170. 2,3,4,5-(CH.sub.3).sub.4 A-171.
2,3,4,6-(CH.sub.3).sub.4 A-172. 2,3,5,6-(CH.sub.3).sub.4 A-173.
2,3,4,5,6-(CH.sub.3).sub.5 A-174. 2-CH.sub.2CH.sub.3 A-175.
3-CH.sub.2CH.sub.3 A-176. 4-CH.sub.2CH.sub.3 A-177.
2,3-(CH.sub.2CH.sub.3).sub.2 A-178. 2,4-(CH.sub.2CH.sub.3).sub.2
A-179. 2,5-(CH.sub.2CH.sub.3).sub.2 A-180.
2,6-(CH.sub.2CH.sub.3).sub.2 A-181. 3,4-(CH.sub.2CH.sub.3).sub.2
A-182. 3,5-(CH.sub.2CH.sub.3).sub.2 A-183.
2,3,4-(CH.sub.2CH.sub.3).sub.3 A-184.
2,3,5-(CH.sub.2CH.sub.3).sub.3 A-185.
2,3,6-(CH.sub.2CH.sub.3).sub.3 A-186.
2,4,5-(CH.sub.2CH.sub.3).sub.3 A-187.
2,4,6-(CH.sub.2CH.sub.3).sub.3 A-188.
3,4,5-(CH.sub.2CH.sub.3).sub.3 A-189.
2,3,4,5-(CH.sub.2CH.sub.3).sub.4 A-190.
2,3,4,6-(CH.sub.2CH.sub.3).sub.4 A-191.
2,3,5,6-(CH.sub.2CH.sub.3).sub.4 A-192.
2,3,4,5,6-(CH.sub.2CH.sub.3).sub.5 A-193.
2-CH.sub.2CH.sub.2CH.sub.3 A-194. 3-CH.sub.2CH.sub.2CH.sub.3 A-195.
4-CH.sub.2CH.sub.2CH.sub.3 A-196.
2,3-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-197.
2,4-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-198.
2,5-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-199.
2,6-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-200.
3,4-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-201.
3,5-(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-202.
2,3,4-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-203.
2,3,5-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-204.
2,3,6-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-205.
2,4,5-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-206.
2,4,6-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-207.
3,4,5-(CH.sub.2CH.sub.2CH.sub.3).sub.3 A-208. 2-CH(CH.sub.3).sub.2
A-209. 3-CH(CH.sub.3).sub.2 A-210. 4-CH(CH.sub.3).sub.2 A-211.
2,4-(CH(CH.sub.3).sub.2).sub.2 A-212.
2,5-(CH(CH.sub.3).sub.2).sub.2 A-213.
2,6-(CH(CH.sub.3).sub.2).sub.2 A-214.
3,5-(CH(CH.sub.3).sub.2).sub.2 A-215.
2,4,6-(CH(CH.sub.3).sub.2).sub.3 A-216.
2-CH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-217.
3-CH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-218.
4-CH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-219.
2,3-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-220.
2,4-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-221.
2,5-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-222. 2,6-
(CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-223.
3,4-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-224.
3,5-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-225.
2,3,4-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-226.
2,3,5-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-227.
2,3,6-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-228.
2,4,5-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-229.
2,4,6-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-230.
3,4,5-(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-231.
2-CH(CH.sub.3)CH.sub.2CH.sub.3 A-232.
3-CH(CH.sub.3)CH.sub.2CH.sub.3 A-233.
4-CH(CH.sub.3)CH.sub.2CH.sub.3 A-234.
2,4-(CH(CH.sub.3)CH.sub.2CH.sub.3).sub.2 A-235.
2,5-(CH(CH.sub.3)CH.sub.2CH.sub.3).sub.2 A-236.
2,6-(CH(CH.sub.3)CH.sub.2CH.sub.3).sub.2 A-237.
3,5-(CH(CH.sub.3)CH.sub.2CH.sub.3).sub.2 A-238.
2,4,6-(CH(CH.sub.3)CH.sub.2CH.sub.3).sub.3 A-239.
2-CH.sub.2CH(CH.sub.3).sub.2 A-240. 3-CH.sub.2CH(CH.sub.3).sub.2
A-241. 4-CH.sub.2CH(CH.sub.3).sub.2 A-242.
2,4-(CH.sub.2CH(CH.sub.3).sub.2).sub.2 A-243.
2,5-(CH.sub.2CH(CH.sub.3).sub.2).sub.2
A-244. 2,6-(CH.sub.2CH(CH.sub.3).sub.2).sub.2 A-245.
3,5-(CH.sub.2CH(CH.sub.3).sub.2).sub.2 A-246.
2,4,6-(CH.sub.2CH(CH.sub.3).sub.2).sub.3 A-247. 2-C(CH.sub.3).sub.3
A-248. 3-C(CH.sub.3).sub.3 A-249. 4-C(CH.sub.3).sub.3 A-250.
2,4-(C(CH.sub.3).sub.3).sub.2 A-251. 2,5-(C(CH.sub.3).sub.3).sub.2
A-252. 2,6-(C(CH.sub.3).sub.3).sub.2 A-253.
3,5-(C(CH.sub.3).sub.3).sub.2 A-254.
2,4,6-(C(CH.sub.3).sub.3).sub.3 A-255. 2-CF.sub.3 A-256. 3-CF.sub.3
A-257. 4-CF.sub.3 A-258. 2,3-(CF.sub.3).sub.2 A-259.
2,4-(CF.sub.3).sub.2 A-260. 2,5-(CF.sub.3).sub.2 A-261.
2,6-(CF.sub.3).sub.2 A-262. 3,4-(CF.sub.3).sub.2 A-263.
3,5-(CF.sub.3).sub.2 A-264. 2,3,4-(CF.sub.3).sub.3 A-265.
2,3,5-(CF.sub.3).sub.3 A-266. 2,3,6-(CF.sub.3).sub.3 A-267.
2,4,6-(CF.sub.3).sub.3 A-268. 3,4,5-(CF.sub.3).sub.3 A-269.
2-CHF.sub.2 A-270. 3-CHF.sub.2 A-271. 4-CHF.sub.2 A-272.
2,3-(CHF.sub.2).sub.2 A-273. 2,4-(CHF.sub.2).sub.2 A-274.
2,5-(CHF.sub.2).sub.2 A-275. 2,6-(CHF.sub.2).sub.2 A-276.
3,4-(CHF.sub.2).sub.2 A-277. 3,5-(CHF.sub.2).sub.2 A-278.
2,3,4-(CHF.sub.2).sub.3 A-279. 2,3,5-(CHF.sub.2).sub.3 A-280.
2,3,6-(CHF.sub.2).sub.3 A-281. 2,4,5-(CHF.sub.2).sub.3 A-282.
2,4,6-(CHF.sub.2).sub.3 A-283. 3,4,5-(CHF.sub.2).sub.3 A-284.
2-CH.sub.2F A-285. 3-CH.sub.2F A-286. 4-CH.sub.2F A-287.
2,3-(CH.sub.2F).sub.2 A-288. 2,4-(CH.sub.2F).sub.2 A-289.
2,5-(CH.sub.2F).sub.2 A-290. 2,6-(CH.sub.2F).sub.2 A-291.
3,4-(CH.sub.2F).sub.2 A-292. 3,5-(CH.sub.2F).sub.2 A-293.
2,3,4-(CH.sub.2F).sub.3 A-294. 2,3,5-(CH.sub.2F).sub.3 A-295.
2,3,6-(CH.sub.2F).sub.3 A-296. 2,4,5-(CH.sub.2F).sub.3 A-297.
2,4,6-(CH.sub.2F).sub.3 A-298. 3,4,5-(CH.sub.2F).sub.3 A-299.
2-OCH.sub.3 A-300. 3-OCH.sub.3 A-301. 4-OCH.sub.3 A-302.
2,3-(OCH.sub.3).sub.2 A-303. 2,4-(OCH.sub.3).sub.2 A-304.
2,5-(OCH.sub.3).sub.2 A-305. 2,6-(OCH.sub.3).sub.2 A-306.
3,4-(OCH.sub.3).sub.2 A-307. 3,5-(OCH.sub.3).sub.2 A-308.
2,3,4-(OCH.sub.3).sub.3 A-309. 2,3,5-(OCH.sub.3).sub.3 A-310.
2,3,6-(OCH.sub.3).sub.3 A-311. 2,4,5-(OCH.sub.3).sub.3 A-312.
2,4,6-(OCH.sub.3).sub.3 A-313. 3,4,5-(OCH.sub.3).sub.3 A-314.
2-OCH.sub.2CH.sub.3 A-315. 3-OCH.sub.2CH.sub.3 A-316.
4-OCH.sub.2CH.sub.3 A-317. 2,3-(OCH.sub.2CH.sub.3).sub.2 A-318.
2,4-(OCH.sub.2CH.sub.3).sub.2 A-319. 2,5-(OCH.sub.2CH.sub.3).sub.2
A-320. 2,6-(OCH.sub.2CH.sub.3).sub.2 A-321.
3,4-(OCH.sub.2CH.sub.3).sub.2 A-322. 3,5-(OCH.sub.2CH.sub.3).sub.2
A-323. 2,3,4-(OCH.sub.2CH.sub.3).sub.3 A-324.
2,3,5-(OCH.sub.2CH.sub.3).sub.3 A-325.
2,3,6-(OCH.sub.2CH.sub.3).sub.3 A-326.
2,4,5-(OCH.sub.2CH.sub.3).sub.3 A-327.
2,4,6-(OCH.sub.2CH.sub.3).sub.3 A-328.
3,4,5-(OCH.sub.2CH.sub.3).sub.3 A-329. 2-OCH.sub.2CH.sub.2CH.sub.3
A-330. 3-OCH.sub.2CH.sub.2CH.sub.3 A-331.
4-OCH.sub.2CH.sub.2CH.sub.3 A-332. 2,3-(OCH.sub.2CH.sub.2CH.sub.3)
A-333. 2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2 A-334.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2 A-335.
2,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.2 A-336.
3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2 A-337.
3,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2 A-338.
2,3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-339.
2,3,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-340.
2,3,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-341.
2,4,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-342.
2,4,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-343.
3,4,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.3 A-344.
2-OCH(CH.sub.3).sub.2 A-345. 3-OCH(CH.sub.3).sub.2 A-346.
4-OCH(CH.sub.3).sub.2 A-347. 2,4-(OCH(CH.sub.3).sub.2).sub.2 A-348.
2,5-(OCH(CH.sub.3).sub.2).sub.2 A-349.
2,6-(OCH(CH.sub.3).sub.2).sub.2 A-350.
3,5-(OCH(CH.sub.3).sub.2).sub.2 A-351.
2,4,6-(OCH(CH.sub.3).sub.2).sub.3 A-352.
2-OCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-353.
3-OCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-354.
4-OCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-355.
2,3-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3) A-356.
2,4-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-357.
2,5-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-358.
2,6-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-359.
3,4-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-360.
3,5-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 A-361.
2,3,4-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-362.
2,3,5-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-363.
2,3,6-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-364.
2,4,5-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-365.
2,4,6-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-366.
3,4,5-(OCH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.3 A-367.
2-OCH.sub.2CH(CH.sub.3).sub.2 A-368. 3-OCH.sub.2CH(CH.sub.3).sub.2
A-369. 4-OCH.sub.2CH(CH.sub.3).sub.2 A-370.
2,3-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-371.
2,4-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-372.
2,5-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-373.
2,6-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-374.
3,4-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-375.
3,5-(OCH.sub.2CH(CH.sub.3).sub.2).sub.2 A-376.
2,3,4-(OCH.sub.2CH(CH.sub.3).sub.2).sub.3 A-377.
2,3,5-(OCH.sub.2CH(CH.sub.3).sub.23).sub.3 A-378.
2,3,6-(OCH.sub.2CH(CH.sub.3).sub.2).sub.3 A-379.
2,4,5-(OCH.sub.2CH(CH.sub.3).sub.2).sub.3 A-380.
2,4,6-(OCH.sub.2CH(CH.sub.3).sub.2).sub.3 A-381.
3,4,5-(OCH.sub.2CH(CH.sub.3).sub.2).sub.3 A-382.
2-OCH.sub.2CH.sub.3, 3-OCH.sub.3 A-383. 2-OCH.sub.2CH.sub.3,
4-OH.sub.3 A-384. 2-OCH.sub.2CH.sub.3, 5-OCH.sub.3 A-385.
2-OCH.sub.2CH.sub.3, 6-OCH.sub.3 A-386. 3-OCH.sub.2CH.sub.3,
4-OCH.sub.3 A-387. 3-OCH.sub.2CH.sub.3, 5-OCH.sub.3 A-388.
3-OCH.sub.2CH.sub.3, 6-OCH.sub.3 A-389. 2-OCH.sub.3,
3-OCH.sub.2CH.sub.3 A-390. 2-OCH.sub.3, 4-OCH.sub.2CH.sub.3 A-391.
3-OCH.sub.3, 4-OCH.sub.2CH.sub.3 A-392. 5-OCH.sub.3,
4-OCH.sub.2CH.sub.3 A-393. 2,3-(OCH.sub.2CCH.sub.3).sub.2, 4-
OCH.sub.3 A-394. 2,3-(OCH.sub.2CH.sub.3).sub.2, 5-OCH.sub.3 A-395.
2,3-(OCH.sub.2CH.sub.3).sub.2, 6-OCH.sub.3 A-396.
2,4-(OCH.sub.2CH.sub.3).sub.2, 3-OCH.sub.3 A-397.
2,4-(OCH.sub.2CH.sub.3).sub.2, 5-OCH.sub.3 A-398.
2,4-(OCH.sub.2CH.sub.3).sub.2, 6-OCH.sub.3 A-399.
2,5-(OCH.sub.2CH.sub.3).sub.2, 3-OCH.sub.3 A-400
2,5-(OCH.sub.2CH.sub.3).sub.2, 4-OCH.sub.3 A-401.
2,5-(OCH.sub.2CH.sub.3).sub.2, 6-OCH.sub.3 A-402.
3,4-(OCH.sub.2CH.sub.3).sub.2, 5-OCH.sub.3 A-403.
3,4-(OCH.sub.2CH.sub.3).sub.2, 2-OCH.sub.3 A-404.
2,6-(OCH.sub.2CH.sub.3).sub.2, 3-OCH.sub.3 A-405.
2,6-(OCH.sub.2CH.sub.3).sub.2, 4-OCH.sub.3 A-406.
3,5-(OCH.sub.2CH.sub.3).sub.2, 4-OCH.sub.3 A-407.
2,3-(OCH.sub.3).sub.2, 4-OCH.sub.2CH.sub.3 A-408.
2,3-(OCH.sub.3).sub.2, 5-OCH.sub.2CH.sub.3 A-409.
2,3-(OCH.sub.3).sub.2, 6-OCH.sub.2CH.sub.3 A-410.
2,4-(OCH.sub.3).sub.2, 3-OCH.sub.2CH.sub.3 A-411.
2,4-(OCH.sub.3).sub.2, 5-OCH.sub.2CH.sub.3 A-412.
2,4-(OCH.sub.3).sub.2, 6-OCH.sub.2CH.sub.3 A-413.
2,5-(OCH.sub.3).sub.2, 3-OCH.sub.2CH.sub.3 A-414.
2,5-(OCH.sub.3).sub.2, 4- OCCH.sub.2CH.sub.3 A-415.
2,5-(OCH.sub.3).sub.2, 6-OCH.sub.2CH.sub.3 A-416.
3,4-(OCH.sub.3).sub.2, 5-OCH.sub.2CH.sub.3 A-417.
3,4-(OCH.sub.3).sub.2, 2-OCH.sub.2CH.sub.3 A-418.
2,6-(OCH.sub.3).sub.2, 3-OCH.sub.2CH.sub.3 A-419.
2,6-(OCH.sub.3).sub.2, 4-OCH.sub.2CH.sub.3 A-420.
3,5-(OCH.sub.3).sub.2, 4-OCH.sub.2CH.sub.3 A-421.
2-OCH.sub.2CH.sub.2CH.sub.3, 3-OCH.sub.3 A-422.
2-OCH.sub.2CH.sub.2CH.sub.3, 4-OH.sub.3 A-423.
2-OCH.sub.2CH.sub.2CH.sub.3, 5-OCH.sub.3 A-424.
2-OCH.sub.2CH.sub.2CH.sub.3, 6-OCH.sub.3 A-425.
3-OCH.sub.2CH.sub.2CH.sub.3, 4-OCH.sub.3 A-426.
3-OCH.sub.2CH.sub.2CH.sub.3, 5-OCH.sub.3 A-427.
3-OCH.sub.2CH.sub.2CH.sub.3, 6-OCH.sub.3 A-428. 2-OCH.sub.3,
3-OCH.sub.2CH.sub.2CH.sub.3 A-429. 2-OCH.sub.3,
4-OCH.sub.2CH.sub.2CH.sub.3 A-430. 3-OCH.sub.3,
4-OCH.sub.2CH.sub.2CH.sub.3 A-431. 5-OCH.sub.3,
4-OCH.sub.2CH.sub.2CH.sub.3 A-432.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OCH.sub.3 A-433.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OCH.sub.3 A-434.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OCH.sub.3 A-435.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OCH.sub.3 A-436.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OCH.sub.3 A-437.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OCH.sub.3 A-438.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OCH.sub.3 A-439.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OCH.sub.3 A-440.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OCH.sub.3 A-441.
3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OCH.sub.3 A-442.
3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 2- OCH.sub.3 A-443.
2,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OCH.sub.3 A-444.
2,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OCH.sub.3 A-445.
3,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OCH.sub.3 A-446.
2,3-(OCH.sub.3).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-447.
2,3-(OCH.sub.3).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-448.
2,3-(OCH.sub.3).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-449.
2,4-(OCH.sub.3).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-450.
2,4-(OCH.sub.3).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-451.
2,4-(OCH.sub.3).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-452.
2,5-(OCH.sub.3).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-453.
2,5-(OCH.sub.3).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-454.
2,5-(OCH.sub.3).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-455.
3,4-(OCH.sub.3).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-456.
3,4-(OCH.sub.3).sub.2, 2- OCH.sub.2CH.sub.2CH.sub.3 A-457.
2,6-(OCH.sub.3).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-458.
2,6-(OCH.sub.3).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-459.
3,5-(OCH.sub.3).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-460.
2-OCH(CH.sub.3).sub.2, 3-OCH.sub.3 A-461. 2-OCH(CH.sub.3).sub.2,
4-OH.sub.3 A-462. 2-OCH(CH.sub.3).sub.2, 5-OCH.sub.3 A-463.
2-OCH(CH.sub.3).sub.2, 6-OCH.sub.3 A-464. 3-OCH(CH.sub.3).sub.2,
4-OCH.sub.3
A-465. 3-OCH(CH.sub.3).sub.2, 5-OCH.sub.3 A-466.
3-OCH(CH.sub.3).sub.2, 6-OCH.sub.3 A-467. 2-OCH.sub.3,
3-OCH(CH.sub.3).sub.2 A-468. 2-OCH.sub.3, 4-OCH(CH.sub.3).sub.2
A-469. 3-OCH.sub.3, 4-OCH(CH.sub.3).sub.2 A-470. 5-OCH.sub.3,
4-OCH(CH.sub.3).sub.2 A-471. 2-OCH.sub.2CH(CH.sub.3).sub.2, 3-
OCH.sub.3 A-472. 2-OCH.sub.2CH(CH.sub.3).sub.2, 4-OH.sub.3 A-473.
2-OCH.sub.2CH(CH.sub.3).sub.2, 5- OCH.sub.3 A-474.
2-OCH.sub.2CH(CH.sub.3).sub.2, 6- OCH.sub.3 A-475.
3-OCH.sub.2CH(CH.sub.3).sub.2, 4- OCH.sub.3 A-476.
3-OCH.sub.2CH(CH.sub.3).sub.2, 5- OCH.sub.3 A-477.
3-OCH.sub.2CH(CH.sub.3).sub.2, 6- OCH.sub.3 A-478. 2-OCH.sub.3, 3-
OCH.sub.2CH(CH.sub.3).sub.2 A-479. 2-OCH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-480. 3-OCH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-481. 5-OCH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-482. 2-OCH.sub.2CH.sub.2CH.sub.3, 3-
OCH.sub.2CH.sub.3 A-483. 2-OCH.sub.2CH.sub.2CH.sub.3, 4-
OCH.sub.2CH.sub.3 A-484. 2-OCH.sub.2CH.sub.2CH.sub.3, 5-
OCH.sub.2CH.sub.3 A-485. 2-OCH.sub.2CH.sub.2CH.sub.3, 6-
OCH.sub.2CH.sub.3 A-486. 3-OCH.sub.2CH.sub.2CH.sub.3, 4-
OCH.sub.2CH.sub.3 A-487. 3-OCH.sub.2CH.sub.2CH.sub.3, 5-
OCH.sub.2CH.sub.3 A-488. 3-OCH.sub.2CH.sub.2CH.sub.3, 6-
OCH.sub.2CH.sub.3 A-489. 2-OCH.sub.2CH.sub.3, 3-
OCH.sub.2CH.sub.2CH.sub.3 A-490. 2-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH.sub.2CH.sub.3 A-491. 3-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH.sub.2CH.sub.3 A-492. 5-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH.sub.2CH.sub.3 A-493. 2-OCH(CH.sub.3).sub.2, 3-
OCH.sub.2CH.sub.3 A-494. 2-OCH(CH.sub.3).sub.2, 4-
OCH.sub.2CH.sub.3 A-495. 2-OCH(CH.sub.3).sub.2, 5-
OCH.sub.2CH.sub.3 A-496. 2-OCH(CH.sub.3).sub.2, 6-
OCH.sub.2CH.sub.3 A-497. 3-OCH(CH.sub.3).sub.2, 4-
OCH.sub.2CH.sub.3 A-498. 3-OCH(CH.sub.3).sub.2, 5-
OCH.sub.2CH.sub.3 A-499. 3-OCH(CH.sub.3).sub.2, 6-
OCH.sub.2CH.sub.3 A-500. 2-OCH.sub.2CH.sub.3, 3-
OCH.sub.2CH(CH.sub.3).sub.2 A-501. 2-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-502. 3-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-503. 5-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-504. 2-OCH.sub.2CH(CH.sub.3).sub.2,
3- OCH.sub.2CH.sub.3 A-505. 2-OCH.sub.2CH(CH.sub.3).sub.2, 4-
OCH.sub.2CH.sub.3 A-506. 2-OCH.sub.2CH(CH.sub.3).sub.2, 5-
OCH.sub.2CH.sub.3 A-507. 2-OCH.sub.2CH(CH.sub.3).sub.2, 6-
OCH.sub.2CH.sub.3 A-508. 3-OCH.sub.2CH(CH.sub.3).sub.2, 4-
OCH.sub.2CH.sub.3 A-509. 3-OCH.sub.2CH(CH.sub.3).sub.2, 5-
OCH.sub.2CH.sub.3 A-510. 3-OCH.sub.2CH(CH.sub.3).sub.2, 6-
OCH.sub.2CH.sub.3 A-511. 2-OCH.sub.2CH.sub.3, 3-
OCH.sub.2CH(CH.sub.3).sub.2 A-512. 2-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-513. 3-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-514. 5-OCH.sub.2CH.sub.3, 4-
OCH.sub.2CH(CH.sub.3).sub.2 A-515. 2-OCF.sub.3 A-516. 3-OCF.sub.3
A-517. 4-OCF.sub.3 A-518. 2,3-(OCF.sub.3).sub.2 A-519.
2,4-(OCF.sub.3).sub.2 A-520. 2,5-(OCF.sub.3).sub.2 A-521.
2,6-(OCF.sub.3).sub.2 A-522. 3,4-(OCF.sub.3).sub.2 A-523.
3,5-(OCF.sub.3).sub.2 A-524. 2,3,4-(OCF.sub.3).sub.3 A-525.
2,3,5-(OCF.sub.3).sub.3 A-526. 2,3,6-(OCF.sub.3).sub.3 A-527.
2,4,5-(OCF.sub.3).sub.3 A-528. 2,4,6-(OCF.sub.3).sub.3 A-529.
3,4,5-(OCF.sub.3).sub.3 A-530. 2-OCHF.sub.2 A-531. 3-OCHF.sub.2
A-532. 4-OCHF.sub.2 A-533. 2,3-(OCHF.sub.2).sub.2 A-534.
2,4-(OCHF.sub.2).sub.2 A-535. 2,5-(OCHF.sub.2).sub.2 A-536.
2,6-(OCHF.sub.2).sub.2 A-537. 3,4-(OCHF.sub.2).sub.2 A-538.
3,5-(OCHF.sub.2).sub.2 A-539. 2,3,4-(OCHF.sub.2).sub.3 A-540.
2,3,5-(OCHF.sub.2).sub.3 A-541. 2,3,6-(OCHF.sub.2).sub.3 A-542.
2,4,5-(OCHF.sub.2).sub.3 A-543. 2,4,6-(OCHF.sub.2).sub.3 A-544.
3,4,5-(OCHF.sub.2).sub.3 A-545. 2-OCH.sub.2F A-546. 3-OCH.sub.2F
A-547. 4-OCH.sub.2F A-548. 2,3-(OCH.sub.2F).sub.2 A-549.
2,4-(OCH.sub.2F).sub.2 A-550. 2,5-(OCH.sub.2F).sub.2 A-551.
2,6-(OCH.sub.2F).sub.2 A-552. 3,4-(OCH.sub.2F).sub.2 A-553.
3,5-(OCH.sub.2F).sub.2 A-554. 2,3,4-(OCH.sub.2F).sub.3 A-555.
2,3,5-(OCH.sub.2F).sub.3 A-556. 2,3,6-(OCH.sub.2F).sub.3 A-557.
2,4,5-(OCH.sub.2F).sub.3 A-558. 2,4,6-(OCH.sub.2F).sub.3 A-559.
3,4,5-(OCH.sub.2F).sub.3 A-560. 2-OCF.sub.2CHF.sub.2 A-561.
3-OCF.sub.2CHF.sub.2 A-562. 4-OCF.sub.2CHF.sub.2 A-563.
2,3-(OCF.sub.2CHF.sub.2).sub.2 A-564.
2,4-(OCF.sub.2CHF.sub.2).sub.2 A-565.
2,5-(OCF.sub.2CHF.sub.2).sub.2 A-566.
2,6-(OCF.sub.2CHF.sub.2).sub.2 A-567.
3,4-(OCF.sub.2CHF.sub.2F).sub.2 A-568.
3,5-(OCF.sub.2CHF.sub.2F).sub.2 A-569.
2,3,4-(OCF.sub.2CHF.sub.2).sub.3 A-570.
2,3,5-(OCF.sub.2CHF.sub.2).sub.3 A-571.
2,3,6-(OCF.sub.2CHF.sub.2).sub.3 A-572.
2,4,5-(OCF.sub.2CHF.sub.2).sub.3 A-573.
2,4,6-(OCF.sub.2CHF.sub.2).sub.3 A-574.
3,4,5-(OCF.sub.2CHF.sub.2).sub.3 A-575. 2-OCH.sub.2CH.sub.2CN
A-576. 3-OCH.sub.2CH.sub.2CN A-577. 4-OCH.sub.2CH.sub.2CN A-578.
2-CH.sub.2--CH.dbd.CH.sub.2 A-579. 3-CH.sub.2--CH.dbd.CH.sub.2
A-580. 3-CH.sub.2--CH.dbd.CH.sub.2 A-581.
2-OCH.sub.2--CH.dbd.CH.sub.2 A-582. 3-OCH.sub.2--CH.dbd.CH.sub.2
A-583. 4-OCH.sub.2--CH.dbd.CH.sub.2 A-584. 2-SCH.sub.3 A-585.
3-SCH.sub.3 A-586. 4-SCH.sub.3 A-587. 2-SCF.sub.3 A-588.
3-SCF.sub.3 A-589. 4-SCF.sub.3 A-590. 2-SO.sub.2CH.sub.3 A-591.
3-SO.sub.2CH.sub.3 A-592. 4-SO.sub.2CH.sub.3 A-593.
2-SO.sub.2CH.sub.3 A-594. 3-SO.sub.2CH.sub.3 A-595.
4-SO.sub.2CH.sub.3 A-596. 2-COCH.sub.3 A-597. 3-COCH.sub.3 A-598.
4-COCH.sub.3 A-599. 2-COOCH.sub.3 A-600. 3-COOCH.sub.3 A-601.
4-COOCH.sub.3 A-602. 2-OCOCH.sub.3 A-603. 3-OCOCH.sub.3 A-604.
4-OCOCH.sub.3 A-605. 2-phenyl A-606. 3-phenyl A-607. 4-phenyl
A-608. 2-(2-fluorophenyl) A-609. 3-(2-fluorophenyl) A-610.
4-(2-fluorophenyl) A-611. 2-(3-fluorophenyl) A-612.
3-(3-fluorophenyl) A-613. 4-(3-fluorophenyl) A-614.
2-(4-fluorophenyl) A-615. 3-(4-fluorophenyl) A-616.
4-(4-fluorophenyl) A-617. 2-(2,3-difluorophenyl) A-618.
3-(2,3-difluorophenyl) A-619. 4-(2,3-difluorophenyl) A-620.
2-(2,4-difluorophenyl) A-621. 3-(2,4-difluorophenyl) A-622.
4-(2,4-difluorophenyl) A-623. 2-(2,5-difluorophenyl) A-624.
3-(2,5-difluorophenyl) A-625. 4-(2,5-difluorophenyl) A-626.
2-(2,6-difluorophenyl) A-627. 3-(2,6-difluorophenyl) A-628.
4-(2,6-difluorophenyl) A-629. 2-(2,3,4-trifluorophenyl) A-630.
3-(2,3,4-trifluorophenyl) A-631. 4-(2,3,4-trifluorophenyl) A-632.
2-(2,3,5-trifluorophenyl) A-633. 3-(2,3,5-trifluorophenyl) A-634.
4-(2,3,5-trifluorophenyl) A-635. 2-(2,3,6-trifluorophenyl) A-636.
3-(2,3,6-trifluorophenyl) A-637. 4-(2,3,6-trifluorophenyl) A-638.
2-(2,4,5-trifluorophenyl) A-639. 3-(2,4,5-trifluorophenyl) A-640.
4-(2,4,5-trifluorophenyl) A-641. 2-(2,4,6-trifluorophenyl) A-642.
3-(2,4,6-trifluorophenyl) A-643. 4-(2,4,6-trifluorophenyl) A-644.
2-(3,4,5-trifluorophenyl) A-645. 3-(3,4,5-trifluorophenyl) A-646.
4-(3,4,5-trifluorophenyl) A-647. 2-(2,3,4,5- tetrafluorophenyl)
A-648. 3-(2,3,4,5- tetrafluorophenyl) A-649. 4-(2,3,4,5-
tetrafluorophenyl) A-650. 2-(2,3,4,6- tetrafluorophenyl) A-651.
3-(2,3,4,6- tetrafluorophenyl) A-652. 4-(2,3,4,6-
tetrafluorophenyl) A-653. 2-(2,3,5,6- tetrafluorophenyl) A-654.
3-(2,3,5,6- tetrafluorophenyl) A-655. 4-(2,3,5,6-
tetrafluorophenyl) A-656. 2-(2,3,4,5,6- pentafluorophenyl) A-657.
3-(2,3,4,5,6- pentafluorophenyl) A-658. 4-(2,3,4,5,6-
pentafluorophenyl) A-659. 2-(2-chlorophenyl) A-660.
3-(2-chlorophenyl)
A-661. 4-(2-chlorophenyl) A-662. 2-(3-chlorophenyl) A-663.
3-(3-chlorophenyl) A-664. 4-(3-chlorophenyl) A-665.
2-(4-chlorophenyl) A-666. 3-(4-chlorophenyl) A-667.
4-(4-chlorophenyl) A-668. 2-(2,3-dichlorophenyl) A-669.
3-(2,3-dichlorophenyl) A-670. 4-(2,3-dichlorophenyl) A-671.
2-(2,4-dichlorophenyl) A-672. 3-(2,4-dichlorophenyl) A-673.
4-(2,4-dichlorophenyl) A-674. 2-(2,5-dichlorophenyl) A-675.
3-(2,5-dichlorophenyl) A-676. 4-(2,5-dichlorophenyl) A-677.
2-(2,6-dichlorophenyl) A-678 3-(2,6-dichlorophenyl) A-679.
4-(2,6-dichlorophenyl) A-680. 2-(2,3,4-trichlorophenyl) A-681.
3-(2,3,4-trichlorophenyl) A-682. 4-(2,3,4-trichlorophenyl) A-683.
2-(2,3,5-trichlorophenyl) A-684. 3-(2,3,5-trichlorophenyl) A-685.
4-(2,3,5-trichlorophenyl) A-686. 2-(2,3,6-trichlorophenyl) A-687.
3-(2,3,6-trichlorophenyl) A-688. 4-(2,3,6-trichlorophenyl) A-689.
2-(2,4,5-trichlorophenyl) A-690. 3-(2,4,5-trichlorophenyl) A-691.
4-(2,4,5-trichlorophenyl) A-692. 2-(2,4,6-trichlorophenyl) A-693.
3-(2,4,6-trichlorophenyl) A-694. 4-(2,4,6-trichlorophenyl) A-695.
2-(3,4,5-trichlorophenyl) A-696. 3-(3,4,5-trichlorophenyl) A-697.
4-(3,4,5-trichlorophenyl) A-698. 2-(2-bromophenyl) A-699.
3-(2-bromophenyl) A-700. 4-(2-bromophenyl) A-701. 2-(3-bromophenyl)
A-702. 3-(3-bromophenyl) A-703. 4-(3-bromophenyl) A-704.
2-(4-bromophenyl) A-705. 3-(4-bromophenyl) A-706. 4-(4-bromophenyl)
A-707. 2-(2,3-dibromophenyl) A-708. 3-(2,3-dibromophenyl) A-709.
4-(2,3-dibromophenyl) A-710. 2-(2,4-dibromophenyl) A-711.
3-(2,4-dibromophenyl) A-712. 4-(2,4-dibromophenyl) A-713.
2-(2,5-dibromophenyl) A-714. 3-(2,5-dibromophenyl) A-715.
4-(2,5-dibromophenyl) A-716. 2-(2,6-dibromophenyl) A-717.
3-(2,6-dibromophenyl) A-718. 4-(2,6-dibromophenyl) A-719.
2-(2-fluoro-3- chlorophenyl) A-720. 3-(2-fluoro-3- chlorophenyl)
A-721. 4-(2-fluoro-3- chlorophenyl) A-722. 2-(2-fluoro-4-
chlorophenyl) A-723. 3-(2-fluoro-4- chlorophenyl) A-724.
4-(2-fluoro-4- chlorophenyl) A-725. 2-(2-fluoro-5- chlorophenyl)
A-726. 3-(2-fluoro-5- chlorophenyl) A-727. 4-(2-fluoro-5-
chlorophenyl) A-728. 2-(2-fluoro-6- chlorophenyl) A-729.
3-(2-fluoro-6- chlorophenyl) A-730. 4-(2-fluoro-6- chlorophenyl)
A-731. 2-(3-fluoro-4- chlorophenyl) A-732. 3-(3-fluoro-4-
chlorophenyl) A-733. 4-(3-fluoro-4- chlorophenyl) A-734.
2-(3-fluoro-5- chlorophenyl) A-735. 3-(3-fluoro-5- chlorophenyl)
A-736. 4-(3-fluoro-5- chlorophenyl) A-737. 2-(3-fluoro-6-
chlorophenyl) A-738. 3-(3-fluoro-6- chlorophenyl) A-739.
4-(3-fluoro-6- chlorophenyl) A-740. 2-(4-fluoro-5- chlorophenyl)
A-741. 3-(4-fluoro-5- chlorophenyl) A-742. 4-(4-fluoro-5-
chlorophenyl) A-743. 2-(3-fluoro-2- chlorophenyl) A-744.
3-(3-fluoro-2- chlorophenyl) A-745. 4-(3-fluoro-2- chlorophenyl)
A-746. 2-(4-fluoro-2- chlorophenyl) A-747. 3-(4-fluoro-2-
chlorophenyl) A-748. 4-(4-fluoro-2- chlorophenyl) A-749.
2-(4-fluoro-5- chlorophenyl) A-750. 3-(4-fluoro-5- chlorophenyl)
A-751. 4-(4-fluoro-5- chlorophenyl) A-752. 2-(2-methylphenyl)
A-753. 3-(2-methylphenyl) A-754. 4-(2-methylphenyl) A-755.
2-(3-methylphenyl) A-756. 3-(3-methylphenyl) A-757.
4-(3-methylphenyl) A-758. 2-(4-methylphenyl) A-759.
3-(4-methylphenyl) A-760. 4-(4-methylphenyl) A-761.
2-(2,3-dimethylphenyl) A-762. 3-(2,3-dimethylphenyl) A-763.
4-(2,3-dimethylphenyl) A-764. 2-(2,4-dimethylphenyl) A-765.
3-(2,4-dimethylphenyl) A-766. 4-(2,4-dimethylphenyl) A-767.
2-(2,5-dimethylphenyl) A-768. 3-(2,5-dimethylphenyl) A-769.
4-(2,5-dimethylphenyl) A-770. 2-(2,6-dimethylphenyl) A-771.
3-(2,6-dimethylphenyl) A-772. 4-(2,6-dimethylphenyl) A-773.
2-(2,3,4-trimethylphenyl) A-774. 3-(2,3,4-trimethylphenyl) A-775.
4-(2,3,4-trimethylphenyl) A-776. 2-(2,3,5-trimethylphenyl) A-777.
3-(2,3,5-trimethylphenyl) A-778. 4-(2,3,5-trimethylphenyl) A-779.
2-(2,3,6-trimethylphenyl) A-780. 3-(2,3,6-trimethylphenyl) A-781.
4-(2,3,6-trimethylphenyl) A-782. 2-(2,4,5-trimethylphenyl) A-783.
3-(2,4,5-trimethylphenyl) A-784. 4-(2,4,5-trimethylphenyl) A-785.
2-(2,4,6-trimethylphenyl) A-786. 3-(2,4,6-trimethylphenyl) A-787.
4-(2,4,6-trimethylphenyl) A-788. 2-(3,4,5-trimethylphenyl) A-789.
3-(3,4,5-trimethylphenyl) A-790. 4-(3,4,5-trimethylphenyl) A-791.
2-(2-methoxyphenyl) A-792. 3-(2-methoxyphenyl) A-793.
4-(2-methoxyphenyl) A-794. 2-(3-methoxyphenyl) A-795.
3-(3-methoxyphenyl) A-796. 4-(3-methoxyphenyl) A-797.
2-(4-methoxyphenyl) A-798. 3-(4-methoxyphenyl) A-799.
4-(4-methoxyphenyl) A-800. 2-(2,3-dimethoxyphenyl) A-801.
3-(2,3-dimethoxyphenyl) A-802. 4-(2,3-dimethoxyphenyl) A-803.
2-(2,4-dimethoxyphenyl) A-804. 3-(2,4-dimethoxyphenyl) A-805.
4-(2,4-dimethoxyphenyl) A-806. 2-(2,5-dimethoxyphenyl) A-807.
3-(2,5-dimethoxyphenyl) A-808. 4-(2,5-dimethoxyphenyl) A-809.
2-(2,6-dimethoxyphenyl) A-810. 3-(2,6-dimethoxyphenyl) A-811.
4-(2,6-dimethoxyphenyl) A-812. 2-(2,3,4- trimethoxyphenyl) A-813.
3-(2,3,4- trimethoxyphenyl) A-814. 4-(2,3,4- trimethoxyphenyl)
A-815. 2-(2,3,5- trimethoxyphenyl) A-816. 3-(2,3,5-
trimethoxyphenyl) A-817. 4-(2,3,5- trimethoxyphenyl) A-818.
2-(2,3,6- trimethoxyphenyl) A-819. 3-(2,3,6- trimethoxyphenyl)
A-820. 4-(2,3,6- trimethoxyphenyl) A-821. 2-(2,4,5-
trimethoxyphenyl) A-822. 3-(2,4,5- trimethoxyphenyl) A-823.
4-(2,4,5- trimethoxyphenyl) A-824. 2-(2,4,6- trimethoxyphenyl)
A-825. 3-(2,4,6- trimethoxyphenyl) A-826. 4-(2,4,6-
trimethoxyphenyl) A-827. 2-(3,4,5- trimethoxyphenyl) A-828.
3-(3,4,5- trimethoxyphenyl) A-829. 4-(3,4,5- trimethoxyphenyl)
A-830. 2-(2- trifluoromethylphenyl) A-831. 3-(2-
trifluoromethylphenyl) A-832. 4-(2- trifluoromethylphenyl) A-833.
2-(3- trifluoromethylphenyl) A-834. 3-(3- trifluoromethylphenyl)
A-835. 4-(3- trifluoromethylphenyl) A-836. 2-(4-
trifluoromethylphenyl) A-837. 3-(4- trifluoromethylphenyl) A-838.
4-(4- trifluoromethylphenyl) A-839. 2-(2- trifluoromethoxyphenyl)
A-840. 3-(2- trifluoromethoxyphenyl) A-841. 4-(2-
trifluoromethoxyphenyl) A-842. 2-(3- trifluoromethoxyphenyl) A-843.
3-(3- trifluoromethoxyphenyl) A-844. 4-(3- trifluoromethoxyphenyl)
A-845. 2-(4-
trifluoromethoxyphenyl) A-846. 3-(4- trifluoromethoxyphenyl) A-847.
4-(4- trifluoromethoxyphenyl) A-848. 2-(2-methylthiophenyl) A-849.
3-(2-methylthiophenyl) A-850. 4-(2-methylthiophenyl) A-851.
2-(3-methylthiophenyl) A-852. 3-(3-methylthiophenyl) A-853.
4-(3-methylthiophenyl) A-854. 2-(4-methylthiophenyl) A-855.
3-(4-methylthiophenyl) A-856. 4-(4-methylthiophenyl) A-857.
2-(2-hydroxyphenyl) A-858. 3-(2-hydroxyphenyl) A-859.
4-(2-hydroxyphenyl) A-860. 2-(3-hydroxyphenyl) A-861.
3-(3-hydroxyphenyl) A-862. 4-(3-hydroxyphenyl) A-863.
2-(4-hydroxyphenyl) A-864. 3-(4-hydroxyphenyl) A-865.
4-(4-hydroxyphenyl) A-866. 2-phenoxy A-867. 3-phenoxy A-868.
4-phenoxy A-869. 2-(4-fluorophenoxy) A-870. 3-(4-fluorophenoxy)
A-871. 4-(4-fluorophenoxy) A-872. 2-(4-chlorophenoxy) A-873.
3-(4-chlorophenoxy) A-874. 4-(4-chlorophenoxy) A-875.
2-(4-methylphenoxy) A-876. 3-(4-methylphenoxy) A-877.
4-(4-methylphenoxy) A-878. 2-(4-tert-butylphenoxy) A-879.
3-(4-tert-butylphenoxy) A-880. 4-(4-tert-butylphenoxy) A-881. 2-(4-
trifluoromethylphenoxy) A-882. 3-(4- trifluoromethylphenoxy) A-883.
4-(4- trifluoromethylphenoxy) A-884. 2-(3- trifluoromethylphenoxy)
A-885. 3-(3- trifluoromethylphenoxy) A-886. 4-(3-
trifluoromethylphenoxy) A-887. 2-(methoxyphenoxy) A-888.
3-(methoxyphenoxy) A-889. 4-(methoxyphenoxy) A-890. 2-
(trifluoromethoxyphenoxy) A-891. 3- (trifluoromethoxyphenoxy)
A-892. 4- (trifluoromethoxyphenoxy) A-893. 2-phenoxymethyl A-894.
3-phenoxymethyl A-895. 4-phenoxymethyl A-896. 2-(4-
fluorophenoxymethyl) A-897. 3-(4- fluorophenoxymethyl) A-898. 4-(4-
fluorophenoxymethyl) A-899. 2-benzoxy A-900. 3-benzoxy A-901.
4-benzoxy A-902. 2-(4-fluorobenzoxy) A-903. 3-(4-fluorobenzoxy)
A-904. 4-(4-fluorobenzoxy) A-905. 2-(4-chlorobenzoxy) A-906.
3-(4-chlorobenzoxy) A-907. 4-(4-chlorobenzoxy) A-908.
2-(4-methylbenzoxy) A-909. 3-(4-methylbenzoxy) A-910.
4-(4-methylbenzoxy) A-911. 2-(4-methoxybenzoxy) A-912.
3-(4-methoxybenzoxy) A-913. 4-(4-methoxybenzoxy) A-914.
2-(4-tert-butylbenzoxy) A-915. 3-(4-tert-butylbenzoxy) A-916.
4-(4-tert-butylbenzoxy) A-917. 2-phenylthio A-918. 3-phenylthio
A-919. 4-phenylthio A-920. 2-phenylsulfonyl A-921. 3-phenylsulfonyl
A-922. 4-phenylsulfonyl A-923. 2-(4-fluorophenylsulfonyl) A-924.
3-(4-fluorophenylsulfonyl) A-925. 4-(4-fluorophenylsulfonyl) A-926.
2-(4-chlorophenylsulfonyl) A-927. 3-(4-chlorophenylsulfonyl) A-928.
4-(4-chlorophenylsulfonyl) A-929. 2-(4- methylphenylsulfonyl)
A-930. 3-(4- methylphenylsulfonyl) A-931. 4-(4-
methylphenylsulfonyl) A-932. 2-OH A-933. 3-OH A-934. 4-OH A-935.
2,3-(OH).sub.2 A-936. 2,4-(OH).sub.2 A-937. 2,5-(OH).sub.2 A-938.
2,6-(OH).sub.2 A-939. 3,4-(OH).sub.2 A-940. 3,5-(OH).sub.2 A-941.
2-CN A-942. 3-CN A-943. 4-CN A-944. 2-NH.sub.2 A-945. 3-NH.sub.2
A-946. 4-NH.sub.2 A-947. 2-NHCH.sub.3 A-948. 3-NHCH.sub.3 A-949.
4-NHCH.sub.3 A-950. 2-NHCH.sub.2CH.sub.3 A-951.
3-NHCH.sub.2CH.sub.3 A-952. 4-NHCH.sub.2CH.sub.3 A-953.
2-NHCH.sub.2CH.sub.2CH.sub.3 A-954. 3-NHCH.sub.2CH.sub.2CH.sub.3
A-955. 4-NHCH.sub.2CH.sub.2CH.sub.3 A-956. 2-NHCH(CH.sub.3).sub.2
A-957. 3-NHCH(CH.sub.3).sub.2 A-958. 4-NHCH(CH.sub.3).sub.2 A-959.
2-NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-960.
3-NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-961.
4-NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3 A-962. 2-N(CH.sub.3).sub.2
A-963. 3-N(CH.sub.3).sub.2 A-964. 4-N(CH.sub.3).sub.2 A-965.
2-N(CH.sub.2CH.sub.3).sub.2 A-966. 3-N(CH.sub.2CH.sub.3).sub.2
A-967. 4-N(CH.sub.2CH.sub.3).sub.2 A-968.
2-N(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-969.
3-N(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-970.
4-N(CH.sub.2CH.sub.2CH.sub.3).sub.2 A-971. 2-NHCHO A-972. 3-NHCHO
A-973. 4-NHCHO A-974. 2-NHC(O)CH.sub.3 A-975. 3-NHC(O)CH.sub.3
A-976. 4-NHC(O)CH.sub.3 A-977. 2-CONH.sub.2 A-978. 3-CONH.sub.2
A-979. 4-CONH.sub.2 A-980. 2-CONHCH.sub.3 A-981. 3-CONHCH.sub.3
A-982. 4-CONHCH.sub.3 A-983. 2-CONHCH.sub.2CH.sub.3 A-984.
3-CONHCH.sub.2CH.sub.3 A-985. 4-CONHCH.sub.2CH.sub.3 A-986.y
2-(1-pyrrolidinyl) A-987. 3-(1-pyrrolidinyl) A-988.
4-(1-pyrrolidinyl) A-989. 2-(1-piperidinyl) A-990.
3-(1-piperidinyl) A-991. 4-(1-piperidinyl) A-992. 2-(1-piperazinyl)
A-993. 3-(1-piperazinyl) A-994. 4-(1-piperazinyl) A-995.
2-(4-methylpiperazin-1-yl) A-996. 3-(4-methylpiperazin-1-yl) A-997.
4-(4-methylpiperazin-1-yl) A-998. 2-(4-morpholinyl) A-999.
3-(4-morpholinyl) A-1000. 4-(4-morpholinyl) A-1001.
2-(4-thiomorpholinyl) A-1002. 3-(4-thiomorpholinyl) A-1003.
4-(4-thiomorpholinyl) A-1004. 2-(pyrrol-1-yl) A-1005.
3-(pyrrol-1-yl) A-1006. 4-(pyrrol-1-yl) A-1007.
2-(2-methylpyrrol-1-yl) A-1008. 3-(2-methylpyrrol-1-yl) A-1009.
4-(2-methylpyrrol-1-yl) A-1010. 2-(2,5-dimethylpyrrol-1-yl) A-1011.
3-(2,5-dimethylpyrrol-1-yl) A-1012. 4-(2,5-dimethylpyrrol-1-yl)
A-1013. 2-(imidazol-1-yl) A-1014. 3-(imidazol-1-yl) A-1015.
4-(imidazol-1-yl) A-1016. 2-F, 3-CH.sub.3 A-1017. 2-F, 4-CH.sub.3
A-1018. 2-F, 5-CH.sub.3 A-1019. 2-F, 6-CH.sub.3 A-1020. 3-F,
4-CH.sub.3 A-1021. 3-F, 5-CH.sub.3 A-1022. 3-F, 6-CH.sub.3 A-1023.
2-CH.sub.3, 3-F A-1024. 2-CH.sub.3, 4-F A-1025. 3-CH.sub.3, 4-F
A-1026. 5-CH.sub.3, 4-F A-1027. 2,3-F.sub.2, 4-CH.sub.3 A-1028.
2,3-F.sub.2, 5-CH.sub.3 A-1029. 2,3-F.sub.2, 6-CH.sub.3 A-1030.
2,4-F.sub.2, 3-CH.sub.3 A-1031. 2,4-F.sub.2, 5-CH.sub.3 A-1032.
2,4-F.sub.2, 6-CH.sub.3 A-1033. 2,5-F.sub.2, 3-CH.sub.3 A-1034.
2,5-F.sub.2, 4-CH.sub.3 A-1035. 2,5-F.sub.2, 6-CH.sub.3 A-1036.
3,4-F.sub.2, 5-CH.sub.3 A-1037. 3,4-F.sub.2, 2-CH.sub.3 A-1038.
2,6-F.sub.2, 3-CH.sub.3 A-1039. 2,6-F.sub.2, 4-CH.sub.3 A-1040.
3,5-F.sub.2, 4-CH.sub.3 A-1041. 2,3-(CH.sub.3).sub.2, 4-F A-1042.
2,3-(CH.sub.3).sub.2, 5-F A-1043. 2,3-(CH.sub.3).sub.2, 6-F A-1044.
2,4-(CH.sub.3).sub.2, 3-F A-1045. 2,4-(CH.sub.3).sub.2, 5-F A-1046.
2,4-(CH.sub.3).sub.2, 6-F A-1047. 2,5-(CH.sub.3).sub.2, 3-F A-1048.
2,5-(CH.sub.3).sub.2, 4-F A-1049. 2,5-(CH.sub.3).sub.2, 6-F A-1050.
3,4-(CH.sub.3).sub.2, 5-F A-1051. 3,4-(CH.sub.3).sub.2, 2-F A-1052.
2,6-(CH.sub.3).sub.2, 3-F A-1053. 2,6-(CH.sub.3).sub.2, 4-F A-1054.
3,5-(CH.sub.3).sub.2, 4-F A-1055. 2-Cl, 3-CH.sub.3 A-1056. 2-Cl,
4-CH.sub.3 A-1057. 2-Cl, 5-CH.sub.3 A-1058. 2-Cl, 6-CH.sub.3
A-1059. 3-Cl, 4-CH.sub.3 A-1060. 3-Cl, 5-CH.sub.3 A-1061. 3-Cl,
6-CH.sub.3 A-1062. 2-CH.sub.3, 3-Cl A-1063. 2-CH.sub.3, 4-Cl
A-1064. 3-CH.sub.3, 4-Cl A-1065. 5-CH.sub.3, 4-Cl A-1066.
2,3-Cl.sub.2, 4-CH.sub.3 A-1067. 2,3-Cl.sub.2, 5-CH.sub.3 A-1068.
2,3-Cl.sub.2, 6-CH.sub.3 A-1069. 2,4-Cl.sub.2, 3-CH.sub.3 A-1070.
2,4-Cl.sub.2, 5-CH.sub.3 A-1071. 2,4-Cl.sub.2, 6-CH.sub.3 A-1072.
2,5-Cl.sub.2, 3-CH.sub.3 A-1073. 2,5-Cl.sub.2, 4-CH.sub.3 A-1074.
2,5-Cl.sub.2, 6-CH.sub.3 A-1075. 3,4-Cl.sub.2, 5-CH.sub.3 A-1076.
3,4-Cl.sub.2, 2-CH.sub.3 A-1077. 2,6-Cl.sub.2, 3-CH.sub.3 A-1078.
2,6-Cl.sub.2, 4-CH.sub.3
A-1079. 3,5-Cl.sub.2, 4-CH.sub.3 A-1080. 2,3-(CH.sub.3).sub.2, 4-Cl
A-1081. 2,3-(CH.sub.3).sub.2, 5-Cl A-1082. 2,3-(CH.sub.3).sub.2,
6-Cl A-1083. 2,4-(CH.sub.3).sub.2, 3-Cl A-1084.
2,4-(CH.sub.3).sub.2, 5-Cl A-1085. 2,4-(CH.sub.3).sub.2, 6-Cl
A-1086. 2,5-(CH.sub.3).sub.2, 3-Cl A-1087. 2,5-(CH.sub.3).sub.2,
4-Cl A-1088. 2,5-(CH.sub.3).sub.2, 6-Cl A-1089.
3,4-(CH.sub.3).sub.2, 5-Cl A-1090. 3,4-(CH.sub.3).sub.2, 2-Cl
A-1091. 2,6-(CH.sub.3).sub.2, 3-Cl A-1092. 2,6-(CH.sub.3).sub.2,
4-Cl A-1093. 3,5-(CH.sub.3).sub.2, 4-Cl A-1094. 2-Br, 3-CH.sub.3
A-1095. 2-Br, 4-CH.sub.3 A-1096. 2-Br, 5-CH.sub.3 A-1097. 2-Br,
6-CH.sub.3 A-1098. 3-Br, 4-CH.sub.3 A-1099. 3-Br, 5-CH.sub.3
A-1100. 3-Br, 6-CH.sub.3 A-1101. 2-CH.sub.3, 3-Br A-1102.
2-CH.sub.3, 4-Br A-1103. 3-CH.sub.3, 4-Br A-1104. 5-CH.sub.3, 4-Br
A-1105. 2,3-Br.sub.2, 4-CH.sub.3 A-1106. 2,3-Br.sub.2, 5-CH.sub.3
A-1107. 2,3-Br.sub.2, 6-CH.sub.3 A-1108. 2,4-Br.sub.2, 3-CH.sub.3
A-1109. 2,4-Br.sub.2, 5-CH.sub.3 A-1110. 2,4-Br.sub.2, 6-CH.sub.3
A-1111. 2,5-Br.sub.2, 3-CH.sub.3 A-1112. 2,5-Br.sub.2, 4-CH.sub.3
A-1113. 2,5-Br.sub.2, 6-CH.sub.3 A-1114. 3,4-Br.sub.2, 5-CH.sub.3
A-1115. 3,4-Br.sub.2, 2-CH.sub.3 A-1116. 2,6-Br.sub.2, 3-CH.sub.3
A-1117. 2,6-Br.sub.2, 4-CH.sub.3 A-1118. 3,5-Br.sub.2, 4-CH.sub.3
A-1119. 2,3-(CH.sub.3).sub.2, 4-Br A-1120. 2,3-(CH.sub.3).sub.2,
5-Br A-1121. 2,3-(CH.sub.3).sub.2, 6-Br A-1122.
2,4-(CH.sub.3).sub.2, 3-Br A-1123. 2,4-(CH.sub.3).sub.2, 5-Br
A-1124. 2,4-(CH.sub.3).sub.2, 6-Br A-1125. 2,5-(CH.sub.3).sub.2,
3-Br A-1126. 2,5-(CH.sub.3).sub.2, 4-Br A-1127.
2,5-(CH.sub.3).sub.2, 6-Br A-1128. 3,4-(CH.sub.3).sub.2, 5-Br
A-1129. 3,4-(CH.sub.3).sub.2, 2-Br A-1130. 2,6-(CH.sub.3).sub.2,
3-Br A-1131. 2,6-(CH.sub.3).sub.2, 4-Br A-1132.
3,5-(CH.sub.3).sub.2, 4-Br A-1133. 2-F, 3-CF.sub.3 A-1134. 2-F,
4-CF.sub.3 A-1135. 2-F, 5-CF.sub.3 A-1136. 2-F, 6-CF.sub.3 A-1137.
3-F, 4-CF.sub.3 A-1138. 3-F, 5-CF.sub.3 A-1139. 3-F, 6-CF.sub.3
A-1140. 2-CF.sub.3, 3-F A-1141. 2-CF.sub.3, 4-F A-1142. 3-CF.sub.3,
4-F A-1143. 5-CF.sub.3, 4-F A-1144. 2,3-F.sub.2, 4-CF.sub.3 A-1145.
2,3-F.sub.2, 5-CF.sub.3 A-1146. 2,3-F.sub.2, 6-CF.sub.3 A-1147.
2,4-F.sub.2, 3-CF.sub.3 A-1148. 2,4-F.sub.2, 5-CF.sub.3 A-1149.
2,4-F.sub.2, 6-CF.sub.3 A-1150. 2,5-F.sub.2, 3-CF.sub.3 A-1151.
2,5-F.sub.2, 4-CF.sub.3 A-1152. 2,5-F.sub.2, 6-CF.sub.3 A-1153.
3,4-F.sub.2, 5-CF.sub.3 A-1154. 3,4-F.sub.2, 2-CF.sub.3 A-1155.
2,6-F.sub.2, 3-CF.sub.3 A-1156. 2,6-F.sub.2, 4-CF.sub.3 A-1157.
3,5-F.sub.2, 4-CF.sub.3 A-1158. 2,3-(CF.sub.3).sub.2, 4-F A-1159.
2,3-(CF.sub.3).sub.2, 5-F A-1160. 2,3-(CF.sub.3).sub.2, 6-F A-1161.
2,4-(CF.sub.3).sub.2, 3-F A-1162. 2,4-(CF.sub.3).sub.2, 5-F A-1163.
2,4-(CF.sub.3).sub.2, 6-F A-1164. 2,5-(CF.sub.3).sub.2, 3-F A-1165.
2,5-(CF.sub.3).sub.2, 4-F A-1166. 2,5-(CF.sub.3).sub.2, 6-F A-1167.
3,4-(CF.sub.3).sub.2, 5-F A-1168. 3,4-(CF.sub.3).sub.2, 2-F A-1169.
2,6-(CF.sub.3).sub.2, 3-F A-1170. 2,6-(CF.sub.3).sub.2, 4-F A-1171.
3,5-(CF.sub.3).sub.2, 4-F A-1172. 2-Cl, 3-CF.sub.3 A-1173. 2-Cl,
4-CF.sub.3 A-1174. 2-Cl, 5-CF.sub.3 A-1175. 2-Cl, 6-CF.sub.3
A-1176. 3-Cl, 4-CF.sub.3 A-1177. 3-Cl, 5-CF.sub.3 A-1178. 3-Cl,
6-CF.sub.3 A-1179. 2-CF.sub.3, 3-Cl A-1180. 2-CF.sub.3, 4-Cl
A-1181. 3-CF.sub.3, 4-Cl A-1182. 5-CF.sub.3, 4-Cl A-1183.
2,3-Cl.sub.2, 4-CF.sub.3 A-1184. 2,3-Cl.sub.2, 5-CF.sub.3 A-1185.
2,3-Cl.sub.2, 6-CF.sub.3 A-1186. 2,4-Cl.sub.2, 3-CF.sub.3 A-1187.
2,4-Cl.sub.2, 5-CF.sub.3 A-1188. 2,4-Cl.sub.2, 6-CF.sub.3 A-1189.
2,5-Cl.sub.2, 3-CF.sub.3 A-1190. 2,5-Cl.sub.2, 4-CF.sub.3 A-1191.
2,5-Cl.sub.2, 6-CF.sub.3 A-1192. 3,4-Cl.sub.2, 5-CF.sub.3 A-1193.
3,4-Cl.sub.2, 2-CF.sub.3 A-1194. 2,6-Cl.sub.2, 3-CF.sub.3 A-1195.
2,6-Cl.sub.2, 4-CF.sub.3 A-1196. 3,5-Cl.sub.2, 4-CF.sub.3 A-1197.
2,3-(CF.sub.3).sub.2, 4-Cl A-1198. 2,3-(CF.sub.3).sub.2, 5-Cl
A-1199. 2,3-(CF.sub.3).sub.2, 6-Cl A-1200. 2,4-(CF.sub.3).sub.2,
3-Cl A-1201. 2,4-(CF.sub.3).sub.2, 5-Cl A-1202.
2,4-(CF.sub.3).sub.2, 6-Cl A-1203. 2,5-(CF.sub.3).sub.2, 3-Cl
A-1204. 2,5-(CF.sub.3).sub.2, 4-Cl A-1205. 2,5-(CF.sub.3).sub.2,
6-Cl A-1206. 3,4-(CF.sub.3).sub.2, 5-Cl A-1207.
3,4-(CF.sub.3).sub.2, 2-Cl A-1208. 2,6-(CF.sub.3).sub.2, 3-Cl
A-1209. 2,6-(CF.sub.3).sub.2, 4-Cl A-1210. 3,5-(CF.sub.3).sub.2,
4-Cl A-1211. 2-Br, 3-CF.sub.3 A-1212. 2-Br, 4-CF.sub.3 A-1213.
2-Br, 5-CF.sub.3 A-1214. 2-Br, 6-CF.sub.3 A-1215. 3-Br, 4-CF.sub.3
A-1216. 3-Br, 5-CF.sub.3 A-1217. 3-Br, 6-CF.sub.3 A-1218.
2-CF.sub.3, 3-Br A-1219. 2-CF.sub.3, 4-Br A-1220. 3-CF.sub.3, 4-Br
A-1221. 5-CF.sub.3, 4-Br A-1222. 2,3-Br.sub.2, 4-CF.sub.3 A-1223.
2,3-Br.sub.2, 5-CF.sub.3 A-1224. 2,3-Br.sub.2, 6-CF.sub.3 A-1225.
2,4-Br.sub.2, 3-CF.sub.3 A-1226. 2,4-Br.sub.2, 5-CF.sub.3 A-1227.
2,4-Br.sub.2, 6-CF.sub.3 A-1228. 2,5-Br.sub.2, 3-CF.sub.3 A-1229.
2,5-Br.sub.2, 4-CF.sub.3 A-1230. 2,5-Br.sub.2, 6-CF.sub.3 A-1231.
3,4-Br.sub.2, 5-CF.sub.3 A-1232. 3,4-Br.sub.2, 2-CF.sub.3 A-1233.
2,6-Br.sub.2, 3-CF.sub.3 A-1234. 2,6-Br.sub.2, 4-CF.sub.3 A-1235.
3,5-Br.sub.2, 4-CF.sub.3 A-1236. 2,3-(CF.sub.3).sub.2, 4-Br A-1237.
2,3-(CF.sub.3).sub.2, 5-Br A-1238. 2,3-(CF.sub.3).sub.2, 6-Br
A-1239. 2,4-(CF.sub.3).sub.2, 3-Br A-1240. 2,4-(CF.sub.3).sub.2,
5-Br A-1241. 2,4-(CF.sub.3).sub.2, 6-Br A-1242.
2,5-(CF.sub.3).sub.2, 3-Br A-1243. 2,5-(CF.sub.3).sub.2, 4-Br
A-1244. 2,5-(CF.sub.3).sub.2, 6-Br A-1245. 3,4-(CF.sub.3).sub.2,
5-Br A-1246. 3,4-(CF.sub.3).sub.2, 2-Br A-1247.
2,6-(CF.sub.3).sub.2, 3-Br A-1248. 2,6-(CF.sub.3).sub.2, 4-Br
A-1249. 3,5-(CF.sub.3).sub.2, 4-Br A-1250. 2-F, 3-OCH.sub.3 A-1251.
2-F, 4-OCH.sub.3 A-1252. 2-F, 5-OCH.sub.3 A-1253. 2-F, 6-OCH.sub.3
A-1254. 3-F, 4-OCH.sub.3 A-1255. 3-F, 5-OCH.sub.3 A-1256. 3-F,
6-OCH.sub.3 A-1257. 2-OCH.sub.3, 3-F A-1258. 2-OCH.sub.3, 4-F
A-1259. 3-OCH.sub.3, 4-F A-1260. 5-OCH.sub.3, 4-F A-1261.
2,3-F.sub.2, 4-OCH.sub.3 A-1262. 2,3-F.sub.2, 5-OCH.sub.3 A-1263.
2,3-F.sub.2, 6-OCH.sub.3 A-1264. 2,4-F.sub.2, 3-OCH.sub.3 A-1265.
2,4-F.sub.2, 5-OCH.sub.3 A-1266. 2,4-F.sub.2, 6-OCH.sub.3 A-1267.
2,5-F.sub.2, 3-OCH.sub.3 A-1268. 2,5-F.sub.2, 4-OCH.sub.3 A-1269.
2,5-F.sub.2, 6-OCH.sub.3 A-1270. 3,4-F.sub.2, 5-OCH.sub.3 A-1271.
3,4-F.sub.2, 2-OCH.sub.3 A-1272. 2,6-F.sub.2, 3-OCH.sub.3 A-1273.
2,6-F.sub.2, 4-OCH.sub.3 A-1274. 3,5-F.sub.2, 4-OCH.sub.3 A-1275.
2,3-(OCH.sub.3).sub.2, 4-F A-1276. 2,3-(OCH.sub.3).sub.2, 5-F
A-1277. 2,3-(OCH.sub.3).sub.2, 6-F A-1278. 2,4-(OCH.sub.3).sub.2,
3-F A-1279. 2,4-(OCH.sub.3).sub.2, 5-F A-1280.
2,4-(OCH.sub.3).sub.2, 6-F A-1281. 2,5-(OCH.sub.3).sub.2, 3-F
A-1282. 2,5-(OCH.sub.3).sub.2, 4-F A-1283. 2,5-(OCH.sub.3).sub.2,
6-F A-1284. 3,4-(OCH.sub.3).sub.2, 5-F A-1285.
3,4-(OCH.sub.3).sub.2, 2-F A-1286. 2,6-(OCH.sub.3).sub.2, 3-F
A-1287. 2,6-(OOH.sub.3).sub.2, 4-F A-1288. 3,5-(OCH.sub.3).sub.2,
4-F A-1289. 2-Cl, 3-OCH.sub.3 A-1290. 2-Cl, 4-OCH.sub.3 A-1291.
2-Cl, 5-OCH.sub.3 A-1292. 2-Cl, 6-OCH.sub.3 A-1293. 3-Cl,
4-OCH.sub.3 A-1294. 3-Cl, 5-OCH.sub.3 A-1295. 3-Cl, 6-OCH.sub.3
A-1296. 2-OCH.sub.3, 3-Cl A-1297. 2-OCH.sub.3, 4-Cl A-1298.
3-OCH.sub.3, 4-Cl A-1299. 5-OCH.sub.3, 4-Cl A-1300. 2,3-Cl.sub.2,
4-OCH.sub.3 A-1301. 2,3-Cl.sub.2, 5-OCH.sub.3 A-1302. 2,3-Cl.sub.2,
6-OCH.sub.3 A-1303. 2,4-Cl.sub.2, 3-OCH.sub.3 A-1304. 2,4-Cl.sub.2,
5-OCH.sub.3 A-1305. 2,4-Cl.sub.2, 6-OCH.sub.3 A-1306. 2,5-Cl.sub.2,
3-OCH.sub.3 A-1307. 2,5-Cl.sub.2, 4-OCH.sub.3 A-1308. 2,5-Cl.sub.2,
6-OCH.sub.3 A-1309. 3,4-Cl.sub.2, 5-OCH.sub.3 A-1310. 3,4-Cl.sub.2,
2-OCH.sub.3 A-1311. 2,6-Cl.sub.2, 3-OCH.sub.3 A-1312. 2,6-Cl.sub.2,
4-OCH.sub.3 A-1313. 3,5-Cl.sub.2, 4-OCH.sub.3 A-1314.
2,3-(OCH.sub.3).sub.2, 4-Cl A-1315. 2,3-(OCH.sub.3).sub.2, 5-Cl
A-1316. 2,3-(OCH.sub.3).sub.2, 6-Cl A-1317. 2,4-(OCH.sub.3).sub.2,
3-Cl A-1318. 2,4-(OCH.sub.3).sub.2, 5-Cl A-1319.
2,4-(OCH.sub.3).sub.2, 6-Cl A-1320. 2,5-(OCH.sub.3).sub.2, 3-Cl
A-1321. 2,5-(OCH.sub.3).sub.2, 4-Cl A-1322. 2,5-(OCH.sub.3).sub.2,
6-Cl A-1323. 3,4-(OCH.sub.3).sub.2, 5-Cl A-1324.
3,4-(OCH.sub.3).sub.2, 2-Cl A-1325. 2,6-(OCH.sub.3).sub.2, 3-Cl
A-1326. 2,6-(OCH.sub.3).sub.2, 4-Cl A-1327. 3,5-(OCH.sub.3).sub.2,
4-Cl A-1328. 3,4-(OCH.sub.3).sub.2, 2,6-Cl.sub.2 A-1329. 2-Br,
3-OCH.sub.3
A-1330. 2-Br, 4-OCH.sub.3 A-1331. 2-Br, 5-OCH.sub.3 A-1332. 2-Br,
6-OCH.sub.3 A-1333. 3-Br, 4-OCH.sub.3 A-1334. 3-Br, 5-OCH.sub.3
A-1335. 3-Br, 6-OCH.sub.3 A-1336. 2-OCH.sub.3, 3-Br A-1337.
2-OCH.sub.3, 4-Br A-1338. 3-OCH.sub.3, 4-Br A-1339. 5-OCH.sub.3,
4-Br A-1340. 2,3-Br.sub.2, 4-OCH.sub.3 A-1341. 2,3-Br.sub.2,
5-OCH.sub.3 A-1342. 2,3-Br.sub.2, 6-OCH.sub.3 A-1343. 2,4-Br.sub.2,
3-OCH.sub.3 A-1344. 2,4-Br.sub.2, 5-OCH.sub.3 A-1345. 2,4-Br.sub.2,
6-OCH.sub.3 A-1346. 2,5-Br.sub.2, 3-OCH.sub.3 A-1347. 2,5-Br.sub.2,
4-OCH.sub.3 A-1348. 2,5-Br.sub.2, 6-OCH.sub.3 A-1349. 3,4-Br.sub.2,
5-OCH.sub.3 A-1350. 3,4-Br.sub.2, 2-OCH.sub.3 A-1351. 2,6-Br.sub.2,
3-OCH.sub.3 A-1352. 2,6-Br.sub.2, 4-OCH.sub.3 A-1353. 3,5-Br.sub.2,
4-OCH.sub.3 A-1354. 2,3-(OCH.sub.3).sub.2, 4-Br A-1355.
2,3-(OCH.sub.3).sub.2, 5-Br A-1356. 2,3-(OCH.sub.3).sub.2, 6-Br
A-1357. 2,4-(OCH.sub.3).sub.2, 3-Br A-1358. 2,4-(OCH.sub.3).sub.2,
5-Br A-1359. 2,4-(OCH.sub.3).sub.2, 6-Br A-1360.
2,5-(OCH.sub.3).sub.2, 3-Br A-1361. 2,5-(OCH.sub.3).sub.2, 4-Br
A-1362. 2,5-(OCH.sub.3).sub.2, 6-Br A-1363. 3,4-(OCH.sub.3).sub.2,
5-Br A-1364. 3,4-(OCH.sub.3).sub.2, 2-Br A-1365.
2,6-(OH.sub.3).sub.2, 3-Br A-1366. 2,6-(OCH.sub.3).sub.2, 4-Br
A-1367. 3,5-(OCH.sub.3).sub.2, 4-Br A-1368. 2-Br,
3-OCH.sub.2CH.sub.3 A-1369. 2-Br, 4-OCH.sub.2CH.sub.3 A-1370. 2-Br,
5-OCH.sub.2CH.sub.3 A-1371. 2-Br, 6-OCH.sub.2CH.sub.3 A-1372. 3-Br,
4-OCH.sub.2CH.sub.3 A-1373. 3-Br, 5-OCH.sub.2CH.sub.3 A-1374. 3-Br,
6-OCH.sub.2CH.sub.3 A-1375. 2-OCH.sub.2CH.sub.3, 3-Br A-1376.
2-OCH.sub.2CH.sub.3, 4-Br A-1377. 3-OCH.sub.2CH.sub.3, 4-Br A-1378.
5-OCH.sub.2CH.sub.3, 4-Br A-1379. 2-I, 3-OCH.sub.3 A-1380. 2-I,
4-OCH.sub.3 A-1381. 2-I, 5-OCH.sub.3 A-1382. 2-I, 6-OCH.sub.3
A-1383. 3-I, 4-OCH.sub.3 A-1384. 3-I, 5-OCH.sub.3 A-1385. 3-I,
6-OCH.sub.3 A-1386. 2-OCH.sub.3, 3-I A-1387. 2-OCH.sub.3, 4-I
A-1388. 3-OCH.sub.3, 4-I A-1389. 5-OCH.sub.3, 4-I A-1390.
2,3-I.sub.2, 4-OCH.sub.3 A-1391. 2,3-I.sub.2, 5-OCH.sub.3 A-1392.
2,3-I.sub.2, 6-OCH.sub.3 A-1393. 2,4-I.sub.2, 3-OCH.sub.3 A-1394.
2,4-I.sub.2, 5-OCH.sub.3 A-1395. 2,4-I.sub.2, 6-OCH.sub.3 A-1396.
2,5-I.sub.2, 3-OCH.sub.3 A-1397. 2,5-I.sub.2, 4-OCH.sub.3 A-1398.
2,5-I.sub.2, 6-OCH.sub.3 A-1399. 3,4-I.sub.2, 5-OCH.sub.3 A-1400.
3,4-I.sub.2, 2-OCH.sub.3 A-1401. 2,6-I.sub.2, 3-OCH.sub.3 A-1402.
2,6-I.sub.2, 4-OCH.sub.3 A-1403. 3,5-I.sub.2, 4-OCH.sub.3 A-1404.
2,3-(OCH.sub.3).sub.2, 4-I A-1405. 2,3-(OCH.sub.3).sub.2, 5-I
A-1406. 2,3-(OCH.sub.3).sub.2, 6-I A-1407. 2,4-(OCH.sub.3).sub.2,
3-I A-1408. 2,4-(OCH.sub.3).sub.2, 5-I A-1409.
2,4-(OCH.sub.3).sub.2, 6-I A-1410.y 2,5-(OCH.sub.3).sub.2, 3-I
A-1411. 2,5-(OCH.sub.3).sub.2, 4-I A-1412. 2,5-(OCH.sub.3).sub.2,
6-I A-1413. 3,4-(OCH.sub.3).sub.2, 5-I A-1414.
3,4-(OCH.sub.3).sub.2, 2-I A-1415. 2,6-(OH.sub.3).sub.2, 3-I
A-1416. 2,6-(OCH.sub.3).sub.2, 4-I A-1417. 3,5-(OCH.sub.3).sub.2,
4-I A-1418. 2-F, 3-OH A-1419. 2-F, 4-OH A-1420. 2-F, 5-OH A-1421.
2-F, 6-OH A-1422. 3-F, 4-OH A-1423. 3-F, 5-OH A-1424. 3-F, 6-OH
A-1425. 2-OH, 3-F A-1426. 2-OH, 4-F A-1427. 3-OH, 4-F A-1428. 5-OH,
4-F A-1429. 2,3-F.sub.2, 4-OH A-1430. 2,3-F.sub.2, 5-OH A-1431.
2,3-F.sub.2, 6-OH A-1432. 2,4-F.sub.2, 3-OH A-1433. 2,4-F.sub.2,
5-OH A-1434. 2,4-F.sub.2, 6-OH A-1435. 2,5-F.sub.2, 3-OH A-1436.
2,5-F.sub.2, 4-OH A-1437. 2,5-F.sub.2, 6-OH A-1438. 3,4-F.sub.2,
5-OH A-1439. 3,4-F.sub.2, 2-OH A-1440. 2,6-F.sub.2, 3-OH A-1441.
2,6-F.sub.2, 4-OH A-1442. 3,5-F.sub.2, 4-OH A-1443. 2,3-(OH).sub.2,
4-F A-1444. 2,3-(OH).sub.2, 5-F A-1445. 2,3-(OH).sub.2, 6-F A-1446.
2,4-(OH).sub.2, 3-F A-1447. 2,4-(OH).sub.2, 5-F A-1448.
2,4-(OH).sub.2, 6-F A-1449. 2,5-(OH).sub.2, 3-F A-1450.
2,5-(OH).sub.2, 4-F A-1451. 2,5-(OH).sub.2, 6-F A-1452.
3,4-(OH).sub.2, 5-F A-1453. 3,4-(OH).sub.2, 2-F A-1454.
2,6-(OH).sub.2, 3-F A-1455. 2,6-(OH).sub.2, 4-F A-1456.
3,5-(OH).sub.2, 4-F A-1457. 2-Cl, 3-OH A-1458. 2-Cl, 4-OH A-1459.
2-Cl, 5-OH A-1460. 2-Cl, 6-OH A-1461. 3-Cl, 4-OH A-1462. 3-Cl, 5-OH
A-1463. 3-Cl, 6-OH A-1464. 2-OH, 3-Cl A-1465. 2-OH, 4-Cl A-1466.
3-OH, 4-Cl A-1467. 5-OH, 4-Cl A-1468. 2,3-Cl.sub.2, 4-OH A-1469.
2,3-Cl.sub.2, 5-OH A-1470. 2,3-Cl.sub.2, 6-OH A-1471. 2,4-Cl.sub.2,
3-OH A-1472. 2,4-Cl.sub.2, 5-OH A-1473. 2,4-Cl.sub.2, 6-OH A-1474.
2,5-Cl.sub.2, 3-OH A-1475. 2,5-Cl.sub.2, 4-OH A-1476. 2,5-Cl.sub.2,
6-OH A-1477. 3,4-Cl.sub.2, 5-OH A-1478. 3,4-Cl.sub.2, 2-OH A-1479.
2,6-Cl.sub.2, 3-OH A-1480. 2,6-Cl.sub.2, 4-OH A-1481. 3,5-Cl.sub.2,
4-OH A-1482. 2,3-(OH).sub.2, 4-Cl A-1483. 2,3-(OH).sub.2, 5-Cl
A-1484. 2,3-(OH).sub.2, 6-Cl A-1485. 2,4-(OH).sub.2, 3-Cl A-1486.
2,4-(OH).sub.2, 5-Cl A-1487. 2,4-(OH).sub.2, 6-Cl A-1488.
2,5-(OH).sub.2, 3-Cl A-1489. 2,5-(OH).sub.2, 4-Cl A-1490.
2,5-(OH).sub.2, 6-Cl A-1491. 3,4-(OH).sub.2, 5-Cl A-1492.
3,4-(OH).sub.2, 2-Cl A-1493. 2,6-(OH).sub.2, 3-Cl A-1494.
2,6-(OH).sub.2, 4-Cl A-1495. 3,5-(OH).sub.2, 4-Cl A-1496. 2-Br,
3-OH A-1497. 2-Br, 4-OH A-1498. 2-Br, 5-OH A-1499. 2-Br, 6-OH
A-1500. 3-Br, 4-OH A-1501. 3-Br, 5-OH A-1502. 3-Br, 6-OH A-1503.
2-OH, 3-Br A-1504. 2-OH, 4-Br A-1505. 3-OH, 4-Br A-1506. 5-OH, 4-Br
A-1507. 2,3-Br.sub.2, 4-OH A-1508. 2,3-Br.sub.2, 5-OH A-1509.
2,3-Br.sub.2, 6-OH A-1510. 2,4-Br.sub.2, 3-OH A-1511. 2,4-Br.sub.2,
5-OH A-1512. 2,4-Br.sub.2, 6-OH A-1513. 2,5-Br.sub.2, 3-OH A-1514.
2,5-Br.sub.2, 4-OH A-1515. 2,5-Br.sub.2, 6-OH A-1516. 3,4-Br.sub.2,
5-OH A-1517. 3,4-Br.sub.2, 2-OH A-1518. 2,6-Br.sub.2, 3-OH A-1519.
2,6-Br.sub.2, 4-OH A-1520. 3,5-Br.sub.2, 4-OH A-1521.
2,3-(OH).sub.2, 4-Br A-1522. 2,3-(OH).sub.2, 5-Br A-1523.
2,3-(OH).sub.2, 6-Br A-1524. 2,4-(OH).sub.2, 3-Br A-1525.
2,4-(OH).sub.2, 5-Br A-1526. 2,4-(OH).sub.2, 6-Br A-1527.
2,5-(OH).sub.2, 3-Br A-1528. 2,5-(OH).sub.2, 4-Br A-1529.
2,5-(OH).sub.2, 6-Br A-1530. 3,4-(OH).sub.2, 5-Br A-1531.
3,4-(OH).sub.2, 2-Br A-1532. 2,6-(OH).sub.2, 3-Br A-1533.
2,6-(OH).sub.2, 4-Br A-1534. 3,5-(OH).sub.2, 4-Br A-1535. 2-OH,
3-CH.sub.3 A-1536. 2-OH, 4-CH.sub.3 A-1537. 2-OH, 5-CH.sub.3
A-1538. 2-OH, 6-CH.sub.3 A-1539. 3-OH, 4-CH.sub.3 A-1540. 3-OH,
5-CH.sub.3 A-1541. 3-OH, 6-CH.sub.3 A-1542. 2-CH.sub.3, 3-OH
A-1543. 2-CH.sub.3, 4-OH A-1544. 3-CH.sub.3, 4-OH A-1545.
5-CH.sub.3, 4-OH A-1546. 2,3-(OH).sub.2, 4-CH.sub.3 A-1547.
2,3-(OH).sub.2, 5-CH.sub.3 A-1548. 2,3-(OH).sub.2, 6-CH.sub.3
A-1549. 2,4-(OH).sub.2, 3-CH.sub.3 A-1550. 2,4-(OH).sub.2,
5-CH.sub.3 A-1551. 2,4-(OH).sub.2, 6-CH.sub.3 A-1552.
2,5-(OH).sub.2, 3-CH.sub.3 A-1553. 2,5-(OH).sub.2, 4-CH.sub.3
A-1554. 2,5-(OH).sub.2, 6-CH.sub.3 A-1555. 3,4-(OH).sub.2,
5-CH.sub.3 A-1556. 3,4-(OH).sub.2, 2-CH.sub.3 A-1557.
2,6-(OH).sub.2, 3-CH.sub.3 A-1558. 2,6-(OH).sub.2, 4-CH.sub.3
A-1559. 3,5-(OH).sub.2, 4-CH.sub.3 A-1560. 2,3-(CH.sub.3).sub.2,
4-OH A-1561. 2,3-(CH.sub.3).sub.2, 5-OH A-1562.
2,3-(CH.sub.3).sub.2, 6-OH A-1563. 2,4-(CH.sub.3).sub.2, 3-OH
A-1564. 2,4-(CH.sub.3).sub.2, 5-OH A-1565. 2,4-(CH.sub.3).sub.2,
6-OH A-1566. 2,5-(CH.sub.3).sub.2, 3-OH A-1567.
2,5-(CH.sub.3).sub.2, 4-OH A-1568. 2,5-(CH.sub.3).sub.2, 6-OH
A-1569. 3,4-(CH.sub.3).sub.2, 5-OH A-1570. 3,4-(CH.sub.3).sub.2,
2-OH A-1571. 2,6-(CH.sub.3).sub.2, 3-OH A-1572.
2,6-(CH.sub.3).sub.2, 4-OH A-1573. 3,5-(CH.sub.3).sub.2, 4-OH
A-1574. 2-OH, 3-OCH.sub.3 A-1575. 2-OH, 4-OCH.sub.3 A-1576. 2-OH,
5-OCH.sub.3 A-1577. 2-OH, 6-OCH.sub.3 A-1578. 3-OH, 4-OCH.sub.3
A-1579. 3-OH, 5-OCH.sub.3 A-1580. 3-OH, 6-OCH.sub.3
A-1581. 2-OCH.sub.3, 3-OH A-1582. 2-OCH.sub.3, 4-OH A-1583.
3-OCH.sub.3, 4-OH A-1584. 5-OCH.sub.3, 4-OH A-1585. 2,3-(OH).sub.2,
4-OCH.sub.3 A-1586. 2,3-(OH).sub.2, 5-OCH.sub.3 A-1587.
2,3-(OH).sub.2, 6-OCH.sub.3 A-1588. 2,4-(OH).sub.2, 3-OCH.sub.3
A-1589. 2,4-(OH).sub.2, 5-OCH.sub.3 A-1590. 2,4-(OH).sub.2,
6-OCH.sub.3 A-1591. 2,5-(OH).sub.2, 3-OCH.sub.3 A-1592.
2,5-(OH).sub.2, 4-OCH.sub.3 A-1593. 2,5-(OH).sub.2, 6-OCH.sub.3
A-1594. 3,4-(OH).sub.2, 5-OCH.sub.3 A-1595. 3,4-(OH).sub.2,
2-OCH.sub.3 A-1596. 2,6-(OH).sub.2, 3-OCH.sub.3 A-1597.
2,6-(OH).sub.2, 4-OCH.sub.3 A-1598. 3,5-(OH).sub.2, 4-OCH.sub.3
A-1599. 2,3-(OCH.sub.3).sub.2, 4-OH A-1600. 2,3-(OCH.sub.3).sub.2,
5-OH A-1601. 2,3-(OCH.sub.3).sub.2, 6-OH A-1602.
2,4-(OCH.sub.3).sub.2, 3-OH A-1603. 2,4-(OCH.sub.3).sub.2, 5-OH
A-1604. 2,4-(OCH.sub.3).sub.2, 6-OH A-1605. 2,5-(OCH.sub.3).sub.2,
3-OH A-1606. 2,5-(OCH.sub.3).sub.2, 4-OH A-1607.
2,5-(OCH.sub.3).sub.2, 6-OH A-1608. 3,4-(OCH.sub.3).sub.2, 5-OH
A-1609. 3,4-(OCH.sub.3).sub.2, 2-OH A-1610. 2,6-(OCH.sub.3).sub.2,
3-OH A-1611. 2,6-(OCH.sub.3).sub.2, 4-OH A-1612.
3,5-(OCH.sub.3).sub.2, 4-OH A-1613. 2-OCH.sub.2CH.sub.2CH.sub.3,
3-OH A-1614. 2-OCH.sub.2CH.sub.2CH.sub.3, 4-OH.sub.3 A-1615.
2-OCH.sub.2CH.sub.2CH.sub.3, 5-OH A-1616.
2-OCH.sub.2CH.sub.2CH.sub.3, 6-OH A-1617.
3-OCH.sub.2CH.sub.2CH.sub.3, 4-OH A-1618.
3-OCH.sub.2CH.sub.2CH.sub.3, 5-OH A-1619.
3-OCH.sub.2CH.sub.2CH.sub.3, 6-OH A-1620. 2-OH,
3-OCH.sub.2CH.sub.2CH.sub.3 A-1621. 2-OH,
4-OCH.sub.2CH.sub.2CH.sub.3 A-1622. 3-OH,
4-OCH.sub.2CH.sub.2CH.sub.3 A-1623. 5-OH,
4-OCH.sub.2CH.sub.2CH.sub.3 A-1624.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OH A-1625.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OH A-1626.
2,3-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OH A-1627.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OH A-1628.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OH A-1629.
2,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OH A-1630.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OH A-1631.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OH A-1632.
2,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 6- OH A-1633.
3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 5- OH A-1634.
3,4-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 2- OH A-1635.
2,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 3- OH A-1636.
2,6-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OH A-1637.
3,5-(OCH.sub.2CH.sub.2CH.sub.3).sub.2, 4- OH A-1638.
2,3-(OH).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-1639.
2,3-(OH).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-1640.
2,3-(OH).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-1641.
2,4-(OH).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-1642.
2,4-(OH).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-1643.
2,4-(OH).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-1644.
2,5-(OH).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-1645.
2,5-(OH).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-1646.
2,5-(OH).sub.2, 6- OCH.sub.2CH.sub.2CH.sub.3 A-1647.
3,4-(OH).sub.2, 5- OCH.sub.2CH.sub.2CH.sub.3 A-1648.
3,4-(OH).sub.2, 2- OCH.sub.2CH.sub.2CH.sub.3 A-1649.
2,6-(OH).sub.2, 3- OCH.sub.2CH.sub.2CH.sub.3 A-1650.
2,6-(OH).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-1651.
3,5-(OH).sub.2, 4- OCH.sub.2CH.sub.2CH.sub.3 A-1652. 2-CH.sub.3,
3-OCH.sub.3 A-1653. 2-CH.sub.3, 4-OCH.sub.3 A-1654. 2-CH.sub.3,
5-OCH.sub.3 A-1655. 2-CH.sub.3, 6-OCH.sub.3 A-1656. 3-CH.sub.3,
4-OCH.sub.3 A-1657. 3-CH.sub.3, 5-OCH.sub.3 A-1658. 3-CH.sub.3,
6-OCH.sub.3 A-1659. 2-OCH.sub.3, 3-CH.sub.3 A-1660. 2-OCH.sub.3,
4-CH.sub.3 A-1661. 3-OCH.sub.3, 4-CH.sub.3 A-1662. 5-OCH.sub.3,
4-CH.sub.3 A-1663. 2,3-(CH.sub.3).sub.2, 4-OCH.sub.3 A-1664.
2,3-(CH.sub.3).sub.2, 5-OCH.sub.3 A-1665. 2,3-(CH.sub.3).sub.2,
6-OCH.sub.3 A-1666. 2,4-(CH.sub.3).sub.2, 3-OCH.sub.3 A-1667.
2,4-(CH.sub.3).sub.2, 5-OCH.sub.3 A-1668. 2,4-(CH.sub.3).sub.2,
6-OCH.sub.3 A-1669. 2,5-(CH.sub.3).sub.2, 3-OCH.sub.3 A-1670.
2,5-(CH.sub.3).sub.2, 4-OCH.sub.3 A-1671. 2,5-(CH.sub.3).sub.2,
6-OCH.sub.3 A-1672. 3,4-(CH.sub.3).sub.2, 5-OCH.sub.3 A-1673.
3,4-(CH.sub.3).sub.2, 2-OCH.sub.3 A-1674. 2,6-(CH.sub.3).sub.2,
3-OCH.sub.3 A-1675. 2,6-(CH.sub.3).sub.2, 4-OCH.sub.3 A-1676.
3,5-(CH.sub.3).sub.2, 4-OCH.sub.3 A-1677. 2,3-(OCH.sub.3).sub.2,
4-CH.sub.3 A-1678. 2,3-(OCH.sub.3).sub.2, 5-CH.sub.3 A-1679.
2,3-(OCH.sub.3).sub.2, 6-CH.sub.3 A-1680. 2,4-(OCH.sub.3).sub.2,
3-CH.sub.3 A-1681. 2,4-(OCH.sub.3).sub.2, 5-CH.sub.3 A-1682.
2,4-(OCH.sub.3).sub.2, 6-CH.sub.3 A-1683. 2,5-(OCH.sub.3).sub.2,
3-CH.sub.3 A-1684. 2,5-(OCH.sub.3).sub.2, 4-CH.sub.3 A-1685.
2,5-(OCH.sub.3).sub.2, 6-CH.sub.3 A-1686. 3,4-(OCH.sub.3).sub.2,
5-CH.sub.3 A-1687. 3,4-(OCH.sub.3).sub.2, 2-CH.sub.3 A-1688.
2,6-(OCH.sub.3).sub.2, 3-CH.sub.3 A-1689. 2,6-(OCH.sub.3).sub.2,
4-CH.sub.3 A-1690. 3,5-(OCH.sub.3).sub.2, 4-CH.sub.3 A-1691. 2-F,
5-Cl, 3-CH.sub.3 A-1692. 6-F, 4-Cl, 3-CH.sub.3 A-1693. 6-F, 2-Cl,
3-CH.sub.3 A-1694. 2-F, 3-Cl, 4-CH.sub.3 A-1695. 3-F, 5-Cl,
4-CH.sub.3 A-1696. 2-F, 3-Cl, 5-CH.sub.3 A-1697. 3-F, 2-Cl,
5-CH.sub.3 A-1698. 3-F, 5-Cl, 4-OH A-1699. 3-F, 4-OH, 5-OCH.sub.3
A-1700. 3-Cl, 4-OH, 5-OCH.sub.3 A-1701. 3-Br, 4-OH, 5-OCH.sub.3
A-1702. 3-I, 4-OH, 5-OCH.sub.3 A-1703. 2-F, 3-OH, 4-OCH.sub.3
A-1704. 2-Cl, 3-OH, 4-OCH.sub.3 A-1705. 2-Br, 3-OH, 4-OCH.sub.3
A-1706. 2,6-Cl.sub.2, 3-OH, 4-OCH.sub.3 A-1707. 2-F, 3-Cl,
5-CF.sub.3 A-1708. 3,5-Cl.sub.2, 4-NH.sub.2 A-1709. 3-OH,
4-COOCH.sub.3 A-1710. 4-OH, 3-CH.sub.2--CH.dbd.CH.sub.2 A-1711.
4-OH, 3-CONH.sub.2 A-1712. 4-OCH.sub.3, 3-O--CH.sub.2-phenyl
A-1713. 4-OCH.sub.3, 3-O--CH.sub.2-(4- fluorophenyl) A-1714.
4-OCH.sub.3, 3-CH.sub.2--O-phenyl A-1715. 3-OCH.sub.2CH.sub.3,
4-CH.sub.2--O- phenyl A-1716. 2-CH.sub.3, 4-CH.sub.2--O-phenyl
A-1717. 3,5-(CH.sub.3).sub.2, 4-CH.sub.2--O- phenyl
TABLE-US-00002 TABLE B B.a ##STR00023## No. R.sup.10 Table B.a
B.a-1 -- B.a-2 3-F B.a-3 4-F B.a-4 5-F B.a-5 6-F B.a-6 3-Cl B.a-7
4-Cl B.a-8 5-Cl B.a-9 6-Cl B.a-10 3-Br B.a-11 4-Br B.a-12 5-Br
B.a-13 6-Br B.a-14 3-CH.sub.3 B.a-15 4-CH.sub.3 B.a-16 5-CH.sub.3
B.a-17 6-CH.sub.3 B.a-18 3-CF.sub.3 B.a-19 4-CF.sub.3 B.a-20
5-CF.sub.3 B.a-21 6-CF.sub.3 B.a-22 3-NH.sub.2 B.a-23 4-NH.sub.2
B.a-24 5-NH.sub.2 B.a-25 6-NH.sub.2 B.a-26 3-N(CH.sub.3).sub.2
B.a-27 4-N(CH.sub.3).sub.2 B.a-28 5-N(CH.sub.3).sub.2 B.a-29
6-N(CH.sub.3).sub.2 B.a.30 6-OCH.sub.3 B.b ##STR00024## No.
R.sup.10 Table B.b B.b-1 -- B.b-2 2-F B.b-3 4-F B.b-4 5-F B.b-5 6-F
B.b-6 2-Cl B.b-7 4-Cl B.b-8 5-Cl B.b-9 6-Cl B.b-10 2-Br B.b-11 4-Br
B.b-12 5-Br B.b-13 6-Br B.b-14 2-CH.sub.3 B.b-15 4-CH.sub.3 B.b-16
5-CH.sub.3 B.b-17 6-CH.sub.3 B.b-18 2-CF.sub.3 B.b-19 4-CF.sub.3
B.b-20 5-CF.sub.3 B.b-21 6-CF.sub.3 B.b-22 2-NH.sub.2 B.b-23
4-NH.sub.2 B.b-24 5-NH.sub.2 B.b-25 6-NH.sub.2 B.b-26
2-N(CH.sub.3).sub.2 B.b-27 4-N(CH.sub.3).sub.2 B.b-28
5-N(CH.sub.3).sub.2 B.b-29 6-N(CH.sub.3).sub.2 B.b.30 6-OCH.sub.3
B.b.31 2-OCH.sub.3 B.c ##STR00025## Table B.c No. R.sup.10 B.c-1 --
B.c-2 2-F B.c-3 3-F B.c-4 5-F B.c-5 6-F B.c-6 2-Cl B.c-7 3-Cl B.c-8
5-Cl B.c-9 6-Cl B.c-10 2-Br B.c-11 3-Br B.c-12 5-Br B.c-13 6-Br
B.c-14 2-CH.sub.3 B.c-15 3-CH.sub.3 B.c-16 5-CH.sub.3 B.c-17
6-CH.sub.3 B.c-18 2-CF.sub.3 B.c-19 3-CF.sub.3 B.c-20 5-CF.sub.3
B.c-21 6-CF.sub.3 B.c-22 2-NH.sub.2 B.c-23 3-NH.sub.2 B.c-24
5-NH.sub.2 B.c-25 6-NH.sub.2 B.c-26 2-N(CH.sub.3).sub.2 B.c-27
3-N(CH.sub.3).sub.2 B.c-28 5-N(CH.sub.3).sub.2 B.c-29
6-N(CH.sub.3).sub.2 B.c.30 6-OCH.sub.3 B.c.31 2-OCH.sub.3
TABLE-US-00003 TABLE C C.a ##STR00026## No. (R.sup.10).sub.n C.a-1.
-- C.a-2. 3-F C.a-3. 4-F C.a-4. 5-F C.a-5. 3,4-F.sub.2 C.a-6.
3,5-F.sub.2 C.a-7. 4,5-F.sub.2 C.a-8. 3-Cl C.a-9. 4-Cl C.a-10. 5-Cl
C.a-11. 3,4-Cl.sub.2 C.a-12. 3,5-Cl.sub.2 C.a-13. 4,5-Cl.sub.2
C.a-14. 3-Br C.a-15. 4-Br C.a-16. 5-Br C.a-17. 3-CH.sub.3 C.a-18.
4-CH.sub.3 C.a-19. 5-CH.sub.3 C.a-20. 3,4-(CH.sub.3).sub.2 C.a-21.
3,5-(CH.sub.3).sub.2 C.a-22. 4,5-(CH.sub.3).sub.2 C.a-23.
3-CH.sub.2CH.sub.3 C.a-24. 4-CH.sub.2CH.sub.3 C.a-25.
5-CH.sub.2CH.sub.3 C.a-26. 3-CH.sub.2CH.sub.2CH.sub.3 C.a-27.
4-CH.sub.2CH.sub.2CH.sub.3 C.a-28. 5-CH.sub.2CH.sub.2CH.sub.3
C.a-29. 3-CH(CH.sub.3).sub.2 C.a-30. 4-CH(CH.sub.3).sub.2 C.a-31.
5-CH(CH.sub.3).sub.2 C.a-32. 3-CF.sub.3 C.a-33. 4-CF.sub.3 C.a-34.
5-CF.sub.3 C.a-35. 3-CHF.sub.2 C.a-36. 4-CHF.sub.2 C.a-37.
5-CHF.sub.2 C.a-38. 3-OH C.a-39. 4-OH C.a-40. 5-OH C.a-41.
3-OCH.sub.3 C.a-42. 4-OCH.sub.3 C.a-43. 5-OCH.sub.3 C.a-44.
3-CH.sub.2CH.sub.2OCH.sub.3 C.a-45. 4-CH.sub.2CH.sub.2OCH.sub.3
C.a-46. 5-CH.sub.2CH.sub.2OCH.sub.3 C.a-47. 3-phenyl C.a-48.
4-phenyl C.a-49. 5-phenyl C.a-50. 3-(2-fluorophenyl) C.a-51.
4-(2-fluorophenyl) C.a-52. 5-(2-fluorophenyl) C.a-53.
3-(3-fluorophenyl) C.a-54. 4-(3-fluorophenyl) C.a-55.
5-(3-fluorophenyl) C.a-56. 3-(4-fluorophenyl) C.a-57.
4-(4-fluorophenyl) C.a-58. 5-(4-fluorophenyl) C.a-59.
3-(2-chlorophenyl) C.a-60. 4-(2-chlorophenyl) C.a-61.
5-(2-chlorophenyl) C.a-62. 3-(3-chlorophenyl) C.a-63.
4-(3-chlorophenyl) C.a-64. 5-(3-chlorophenyl) C.a-65.
3-(4-chlorophenyl) C.a-66. 4-(4-chlorophenyl) C.a-67.
5-(4-chlorophenyl) C.a-68. 3-(2-bromophenyl) C.a-69.
4-(2-bromophenyl) C.a-70. 5-(2-bromophenyl) C.a-71.
3-(3-bromophenyl) C.a-72. 4-(3-bromophenyl) C.a-73.
5-(3-bromophenyl) C.a-74. 3-(4-bromophenyl) C.a-75.
4-(4-bromophenyl) C.a-76. 5-(4-bromophenyl) C.a-77.
3-(2,3-dichlorophenyl) C.a-78. 4-(2,3-dichlorophenyl) C.a-79.
5-(2,3-dichlorophenyl) C.a-80. 3-(3,4-dichlorophenyl) C.a-81.
4-(3,4-dichlorophenyl) C.a-82. 5-(3,4-dichlorophenyl) C.a-83.
3-(2,4-dichlorophenyl) C.a-84. 4-(2,4-dichlorophenyl) C.a-85.
5-(2,4-dichlorophenyl) C.a-86. 3-(2,5-dichlorophenyl) C.a-87.
4-(2,5-dichlorophenyl) C.a-88. 5-(2,5-dichlorophenyl) C.a-89.
3-(2-fluoro-6-chlorophenyl) C.a-90. 4-(2-fluoro-6-chlorophenyl)
C.a-91. 5-(2-fluoro-6-chlorophenyl) C.a-92.
3-(2,5-dichloro-3-fluorophenyl) C.a-93.
4-(2,5-dichloro-3-fluorophenyl) C.a-94.
5-(2,5-dichloro-3-fluorophenyl) C.a-95. 3-(2-methylphenyl) C.a-96.
4-(2-methylphenyl) C.a-97. 5-(2-methylphenyl) C.a-98.
3-(3-methylphenyl) C.a-99. 4-(3-methylphenyl) C.a-100.
5-(3-methylphenyl) C.a-101. 3-(4-methylphenyl) C.a-102.
4-(4-methylphenyl) C.a-103. 5-(4-methylphenyl) C.a-104.
3-(2,3-dimethylphenyl) C.a-105. 4-(2,3-dimethylphenyl) C.a-106.
5-(2,3-dimethylphenyl) C.a-107. 3-(2,4-dimethylphenyl) C.a-108.
4-(2,4-dimethylphenyl) C.a-109. 5-(2,4-dimethylphenyl) C.a-110.
3-(2,5-dimethylphenyl) C.a-111. 4-(2,5-dimethylphenyl) C.a-112.
5-(2,5-dimethylphenyl) C.a-113. 3-(3,5-dimethylphenyl) C.a-114.
4-(3,5-dimethylphenyl) C.a-115. 5-(3,5-dimethylphenyl) C.a-116.
3-(2-isopropylphenyl) C.a-117. 4-(2-isopropylphenyl) C.a-118.
5-(2-isopropylphenyl) C.a-119. 3-(3-isopropylphenyl) C.a-120.
4-(3-isopropylphenyl) C.a-121. 5-(3-isopropylphenyl) C.a-122.
3-(4-isopropylphenyl) C.a-123. 4-(4-isopropylphenyl) C.a-124.
5-(4-isopropylphenyl) C.a-125. 3-(2-tert-butylphenyl) C.a-126.
4-(2-tert-butylphenyl) C.a-127. 5-(2-tert-butylphenyl) C.a-128.
3-(3-tert-butylphenyl) C.a-129. 4-(3-tert-butylphenyl) C.a-130.
5-(3-tert-butylphenyl) C.a-131. 3-(4-tert-butylphenyl) C.a-132.
4-(4-tert-butylphenyl) C.a-133. 5-(4-tert-butylphenyl) C.a-134.
3-(2-methoxyphenyl) C.a-135. 4-(2-methoxyphenyl) C.a-136.
5-(2-methoxyphenyl) C.a-137. 3-(3-methoxyphenyl) C.a-138.
4-(3-methoxyphenyl) C.a-139. 5-(3-methoxyphenyl) C.a-140.
3-(4-methoxyphenyl) C.a-141. 4-(4-methoxyphenyl) C.a-142.
5-(4-methoxyphenyl) C.a-143. 3-(2,3-dimethoxyphenyl) C.a-144.
4-(2,3-dimethoxyphenyl) C.a-145. 5-(2,3-dimethoxyphenyl) C.a-146.
3-(2,4-dimethoxyphenyl) C.a-147. 4-(2,4-dimethoxyphenyl) C.a-148.
5-(2,4-dimethoxyphenyl) C.a-149. 3-(2,5-dimethoxyphenyl) C.a-150.
4-(2,5-dimethoxyphenyl) C.a-151. 5-(2,5-dimethoxyphenyl) C.a-152.
3-(3,5-dimethoxyphenyl) C.a-153. 4-(3,5-dimethoxyphenyl) C.a-154.
5-(3,5-dimethoxyphenyl) C.a-155. 3-(2,3,4-trimethoxyphenyl)
C.a-156. 4-(2,3,4-trimethoxyphenyl) C.a-157.
5-(2,3,4-trimethoxyphenyl) C.a-158. 3-(3,4,5-trimethoxyphenyl)
C.a-159. 4-(3,4,5-trimethoxyphenyl) C.a-160.
5-(3,4,5-trimethoxyphenyl) C.a-161. 3-(2-ethoxyphenyl) C.a-162.
4-(2-ethoxyphenyl) C.a-163. 5-(2-ethoxyphenyl) C.a-164.
3-(3-ethoxyphenyl) C.a-165. 4-(3-ethoxyphenyl) C.a-166.
5-(3-ethoxyphenyl) C.a-167. 3-(4-ethoxyphenyl) C.a-168.
4-(4-ethoxyphenyl) C.a-169. 5-(4-ethoxyphenyl) C.a-170.
3-(4-benzyloxyphenyl) C.a-171. 4-(4-benzyloxyphenyl) C.a-172.
5-(4-benzyloxyphenyl) C.a-173. 3-(pyrid-2-yl) C.a-174.
4-(pyrid-2-yl) C.a-175. 5-(pyrid-2-yl) C.a-176. 3-(pyrid-3-yl)
C.a-177. 4-(pyrid-3-yl) C.a-178. 5-(pyrid-3-yl) C.a-179.
3-(pyrid-4-yl) C.a-180. 4-(pyrid-4-yl) C.a-181. 5-(pyrid-4-yl)
C.a-182. 3-(furan-2-yl) C.a-183. 4-(furan-2-yl) C.a-184.
5-(furan-2-yl) C.a-185. 3-(furan-3-yl) C.a-186. 4-(furan-3-yl)
C.a-187. 5-(furan-3-yl) C.a-188. 3-(thien-2-yl) C.a-189.
4-(thien-2-yl) C.a-190. 5-(thien-2-yl) C.a-191. 3-(thien-3-yl)
C.a-192. 4-(thien-3-yl) C.a-193. 5-(thien-3-yl) C.b ##STR00027##
No. (R.sup.10).sub.n C.b-1. -- C.b-2. 2-F C.b-3. 4-F C.b-4. 5-F
C.b-5. 2,4-F.sub.2 C.b-6. 2,5-F.sub.2 C.b-7. 4,5-F.sub.2 C.b-8.
2-Cl C.b-9. 4-Cl C.b-10. 5-Cl C.b-11. 2,4-Cl.sub.2 C.b-12.
2,5-Cl.sub.2 C.b-13. 4,5-Cl.sub.2 C.b-14. 2-Br C.b-15. 4-Br C.b-16.
5-Br C.b-17. 2-CH.sub.3 C.b-18. 4-CH.sub.3 C.b-19. 5-CH.sub.3
C.b-20. 2,4-(CH.sub.3).sub.2 C.b-21. 2,5-(CH.sub.3).sub.2 C.b-22.
4,5-(CH.sub.3).sub.2 C.b-23. 2-CH.sub.2CH.sub.3 C.b-24.
4-CH.sub.2CH.sub.3 C.b-25. 5-CH.sub.2CH.sub.3 C.b-26.
2-CH.sub.2CH.sub.2CH.sub.3 C.b-27. 4-CH.sub.2CH.sub.2CH.sub.3
C.b-28. 5-CH.sub.2CH.sub.2CH.sub.3 C.b-29. 2-CH(CH.sub.3).sub.2
C.b-30. 4-CH(CH.sub.3).sub.2 C.b-31. 5-CH(CH.sub.3).sub.2 C.b-32.
2-CF.sub.3 C.b-33. 4-CF.sub.3 C.b-34. 5-CF.sub.3 C.b-35.
2-CHF.sub.2 C.b-36. 4-CHF.sub.2 C.b-37. 5-CHF.sub.2 C.b-38. 2-OH
C.b-39. 4-OH C.b-40. 5-OH C.b-41. 2-OCH.sub.3 C.b-42. 4-OCH.sub.3
C.b-43. 5-OCH.sub.3 C.b-44. 2-CH.sub.2CH.sub.2OCH.sub.3
C.b-45. 4-CH.sub.2CH.sub.2OCH.sub.3 C.b-46.
5-CH.sub.2CH.sub.2OCH.sub.3 C.b-47. 2-phenyl C.b-48. 4-phenyl
C.b-49. 5-phenyl C.b-50. 2-(2-fluorophenyl) C.b-51.
4-(2-fluorophenyl) C.b-52. 5-(2-fluorophenyl) C.b-53.
2-(3-fluorophenyl) C.b-54. 4-(3-fluorophenyl) C.b-55.
5-(3-fluorophenyl) C.b-56. 2-(4-fluorophenyl) C.b-57.
4-(4-fluorophenyl) C.b-58. 5-(4-fluorophenyl) C.b-59.
2-(2-chlorophenyl) C.b-60. 4-(2-chlorophenyl) C.b-61.
5-(2-chlorophenyl) C.b-62. 2-(3-chlorophenyl) C.b-63.
4-(3-chlorophenyl) C.b-64. 5-(3-chlorophenyl) C.b-65.
2-(4-chlorophenyl) C.b-66. 4-(4-chlorophenyl) C.b-67.
5-(4-chlorophenyl) C.b-68. 2-(2-bromophenyl) C.b-69.
4-(2-bromophenyl) C.b-70. 5-(2-bromophenyl) C.b-71.
2-(3-bromophenyl) C.b-72. 4-(3-bromophenyl) C.b-73.
5-(3-bromophenyl) C.b-74. 2-(4-bromophenyl) C.b-75.
4-(4-bromophenyl) C.b-76. 5-(4-bromophenyl) C.b-77.
2-(2,3-dichlorophenyl) C.b-78. 4-(2,3-dichlorophenyl) C.b-79.
5-(2,3-dichlorophenyl) C.b-80. 2-(3,4-dichlorophenyl) C.b-81.
4-(3,4-dichlorophenyl) C.b-82. 5-(3,4-dichlorophenyl) C.b-83.
2-(2,4-dichlorophenyl) C.b-84. 4-(2,4-dichlorophenyl) C.b-85.
5-(2,4-dichlorophenyl) C.b-86. 2-(2,5-dichlorophenyl) C.b-87.
4-(2,5-dichlorophenyl) C.b-88. 5-(2,5-dichlorophenyl) C.b-89.
2-(2-fluoro-6-chlorophenyl) C.b-90. 4-(2-fluoro-6-chlorophenyl)
C.b-91. 5-(2-fluoro-6-chlorophenyl) C.b-92.
2-(2,5-dichloro-3-fluorophenyl) C.b-93.
4-(2,5-dichloro-3-fluorophenyl) C.b-94.
5-(2,5-dichloro-3-fluorophenyl) C.b-95. 2-(2-methylphenyl) C.b-96.
4-(2-methylphenyl) C.b-97. 5-(2-methylphenyl) C.b-98.
2-(3-methylphenyl) C.b-99. 4-(3-methylphenyl) C.b-100.
5-(3-methylphenyl) C.b-101. 2-(4-methylphenyl) C.b-102.
4-(4-methylphenyl) C.b-103. 5-(4-methylphenyl) C.b-104.
2-(2,3-dimethylphenyl) C.b-105. 4-(2,3-dimethylphenyl) C.b-106.
5-(2,3-dimethylphenyl) C.b-107. 2-(2,4-dimethylphenyl) C.b-108.
4-(2,4-dimethylphenyl) C.b-109. 5-(2,4-dimethylphenyl) C.b-110.
2-(2,5-dimethylphenyl) C.b-111. 4-(2,5-dimethylphenyl) C.b-112.
5-(2,5-dimethylphenyl) C.b-113. 2-(3,5-dimethylphenyl) C.b-114.
4-(3,5-dimethylphenyl) C.b-115. 5-(3,5-dimethylphenyl) C.b-116.
2-(2-isopropylphenyl) C.b-117. 4-(2-isopropylphenyl) C.b-118.
5-(2-isopropylphenyl) C.b-119. 2-(3-isopropylphenyl) C.b-120.
4-(3-isopropylphenyl) C.b-121. 5-(3-isopropylphenyl) C.b-122.
2-(4-isopropylphenyl) C.b-123. 4-(4-isopropylphenyl) C.b-124.
5-(4-isopropylphenyl) C.b-125. 2-(2-tert-butylphenyl) C.b-126.
4-(2-tert-butylphenyl) C.b-127. 5-(2-tert-butylphenyl) C.b-128.
2-(3-tert-butylphenyl) C.b-129. 4-(3-tert-butylphenyl) C.b-130.
5-(3-tert-butylphenyl) C.b-131. 2-(4-tert-butylphenyl) C.b-132.
4-(4-tert-butylphenyl) C.b-133. 5-(4-tert-butylphenyl) C.b-134.
2-(2-methoxyphenyl) C.b-135. 4-(2-methoxyphenyl) C.b-136.
5-(2-methoxyphenyl) C.b-137. 2-(3-methoxyphenyl) C.b-138.
4-(3-methoxyphenyl) C.b-139. 5-(3-methoxyphenyl) C.b-140.
2-(4-methoxyphenyl) C.b-141. 4-(4-methoxyphenyl) C.b-142.
5-(4-methoxyphenyl) C.b-143. 2-(2,3-dimethoxyphenyl) C.b-144.
4-(2,3-dimethoxyphenyl) C.b-145. 5-(2,3-dimethoxyphenyl) C.b-146.
2-(2,4-dimethoxyphenyl) C.b-147. 4-(2,4-dimethoxyphenyl) C.b-148.
5-(2,4-dimethoxyphenyl) C.b-149. 2-(2,5-dimethoxyphenyl) C.b-150.
4-(2,5-dimethoxyphenyl) C.b-151. 5-(2,5-dimethoxyphenyl) C.b-152.
2-(3,5-dimethoxyphenyl) C.b-153. 4-(3,5-dimethoxyphenyl) C.b-154.
5-(3,5-dimethoxyphenyl) C.b-155. 2-(2,3,4-trimethoxyphenyl)
C.b-156. 4-(2,3,4-trimethoxyphenyl) C.b-157.
5-(2,3,4-trimethoxyphenyl) C.b-158. 2-(3,4,5-trimethoxyphenyl)
C.b-159. 4-(3,4,5-trimethoxyphenyl) C.b-160.
5-(3,4,5-trimethoxyphenyl) C.b-161. 2-(2-ethoxyphenyl) C.b-162.
4-(2-ethoxyphenyl) C.b-163. 5-(2-ethoxyphenyl) C.b-164.
2-(3-ethoxyphenyl) C.b-165. 4-(3-ethoxyphenyl) C.b-166.
5-(3-ethoxyphenyl) C.b-167. 2-(4-ethoxyphenyl) C.b-168.
4-(4-ethoxyphenyl) C.b-169. 5-(4-ethoxyphenyl) C.b-170.
2-(4-benzyloxyphenyl) C.b-171. 4-(4-benzyloxyphenyl) C.b-172.
5-(4-benzyloxyphenyl) C.b-173. 2-(pyrid-2-yl) C.b-174.
4-(pyrid-2-yl) C.b-175. 5-(pyrid-2-yl) C.b-176. 2-(pyrid-3-yl)
C.b-177. 4-(pyrid-3-yl) C.b-178. 5-(pyrid-3-yl) C.b-179.
2-(pyrid-4-yl) C.b-180. 4-(pyrid-4-yl) C.b-181. 5-(pyrid-4-yl)
C.b-182. 2-(furan-2-yl) C.b-183. 4-(furan-2-yl) C.b-184.
5-(furan-2-yl) C.b-185. 2-(furan-3-yl) C.b-186. 4-(furan-3-yl)
C.b-187. 5-(furan-3-yl) C.b-188. 2-(thien-2-yl) C.b-189.
4-(thien-2-yl) C.b-190. 5-(thien-2-yl) C.b-191. 2-(thien-3-yl)
C.b-192. 4-(thien-3-yl) C.b-193. 5-(thien-3-yl) X = O, S or
NR.sup.101
TABLE-US-00004 TABLE D D.a ##STR00028## No. (R.sup.10).sub.n D.a-1.
-- D.a-2. 3-F D.a-3. 4-F D.a-4. 3,4-F.sub.2 D.a-5. 3-Cl D.a-6. 4-Cl
D.a-7. 3,4-Cl.sub.2 D.a-8. 3-Br D.a-9. 4-Br D.a-10. 3-CH.sub.3
D.a-11. 4-CH.sub.3 D.a-12. 3,4-(CH.sub.3).sub.2 D.a-13.
3-CH.sub.2CH.sub.3 D.a-14. 4-CH.sub.2CH.sub.3 D.a-15.
3-CH.sub.2CH.sub.2CH.sub.3 D.a-16. 4-CH.sub.2CH.sub.2CH.sub.3
D.a-17. 3-CH(CH.sub.3).sub.2 D.a-18. 4-CH(CH.sub.3).sub.2 D.a-19.
3-CF.sub.3 D.a-20. 4-CF.sub.3 D.a-21. 3-CHF.sub.2 D.a-22.
4-CHF.sub.2 D.a-23. 3-OH D.a-24. 4-OH D.a-25. 3-OCH.sub.3 D.a-26.
4-OCH.sub.3 D.a-27. 3-CH.sub.2CH.sub.2OCH.sub.3 D.a-28.
4-CH.sub.2CH.sub.2OCH.sub.3 D.a-29. 3-phenyl D.a-30. 4-phenyl
D.a-31. 3-(2- fluorophenyl) D.a-32. 4-(2- fluorophenyl) D.a-33.
3-(3- fluorophenyl) D.a-34. 4-(3- fluorophenyl) D.a-35. 3-(4-
fluorophenyl) D.a-36. 4-(4- fluorophenyl) D.a-37. 3-(2-
chlorophenyl) D.a-38. 4-(2- chlorophenyl) D.a-39. 3-(3-
chlorophenyl) D.a-40. 4-(3- chlorophenyl) D.a-41. 3-(4-
chlorophenyl) D.a-42. 4-(4- chlorophenyl) D.a-43. 3-(2-
bromophenyl) D.a-44. 4-(2- bromophenyl) D.a-45. 3-(3- bromophenyl)
D.a-46. 4-(3- bromophenyl) D.a-47. 3-(4- bromophenyl) D.a-48. 4-(4-
bromophenyl) D.a-49. 3-(2,3- dichlorophenyl) D.a-50. 4-(2,3-
dichlorophenyl) D.a-51. 3-(3,4- dichlorophenyl) D.a-52. 4-(3,4-
dichlorophenyl) D.a-53. 3-(2,4- dichlorophenyl) D.a-54. 4-(2,4-
dichlorophenyl) D.a-55. 3-(2,5- dichlorophenyl) D.a-56. 4-(2,5-
dichlorophenyl) D.a-57. 3-(2-fluoro-6- chlorophenyl) D.a-58.
4-(2-fluoro-6- chlorophenyl) D.a-59. 3-(2,5-dichloro-
3-fluorophenyl) D.a-60. 4-(2,5-dichloro- 3-fluorophenyl) D.a-61.
3-(2- methylphenyl) D.a-62. 4-(2- methylphenyl) D.a-63. 3-(3-
methylphenyl) D.a-64. 4-(3- methylphenyl) D.a-65. 3-(4-
methylphenyl) D.a-66. 4-(4- methylphenyl) D.a-67. 3-(2,3-
dimethylphenyl) D.a-68. 4-(2,3- dimethylphenyl) D.a-69. 3-(2,4-
dimethylphenyl) D.a-70. 4-(2,4- dimethylphenyl) D.a-71. 3-(2,5-
dimethylphenyl) D.a-72. 4-(2,5- dimethylphenyl) D.a-73. 3-(3,5-
dimethylphenyl) D.a-74. 4-(3,5- dimethylphenyl) D.a-75. 3-(2-
isopropyl- phenyl) D.a-76. 4-(2- isopropyl- phenyl) D.a-77. 3-(3-
isopropylphe- nyl) D.a-78. 4-(3-iso- propylphenyl) D.a-79.
3-(4-iso- propylphenyl) D.a-80. 4-(4-iso- propylphenyl) D.a-81.
3-(2-tert- butylphenyl) D.a-82. 4-(2-tert- butylphenyl) D.a-83.
3-(3-tert- butylphenyl) D.a-84. 4-(3-tert- butylphenyl) D.a-85.
3-(4-tert- butylphenyl) D.a-86. 4-(4-tert- butylphenyl) D.a-87.
3-(2- methoxyphenyl) D.a-88. 4-(2- methoxyphenyl) D.a-89. 3-(3-
methoxyphenyl) D.a-90. 4-(3- methoxyphenyl) D.a-91. 3-(4-
methoxyphenyl) D.a-92. 4-(4- methoxyphenyl) D.a-93. 3-(2,3-dime-
thoxyphenyl) D.a-94. 4-(2,3-dime- thoxyphenyl) D.a-95. 3-(2,4-dime-
thoxyphenyl) D.a-96. 4-(2,4-dime- thoxyphenyl) D.a-97. 3-(2,5-dime-
thoxyphenyl) D.a-98. 4-(2,5-dime- thoxyphenyl) D.a-99. 3-(3,5-dime-
thoxyphenyl) D.a-100 4-(3,5-dime- thoxyphenyl) D.a-101
3-(2,3,4-trime- thoxyphenyl) D.a-102 4-(2,3,4-trime- thoxyphenyl)
D.a-103 3-(3,4,5-trime- thoxyphenyl) D.a-104 4-(3,4,5-trime-
thoxyphenyl) D.a-105 3-(2- ethoxyphenyl) D.a-106 4-(2-
ethoxyphenyl) D.a-107 3-(3- ethoxyphenyl) D.a-108 4-(3-
ethoxyphenyl) D.a-109 3-(4- ethoxyphenyl) D.a-110 4-(4-
ethoxyphenyl) D.a-111 3-(4-benzyl- oxyphenyl) D.a-112 4-(4-benzyl-
oxyphenyl) D.a-113 3-(pyrid-2-yl) D.a-114 4-(pyrid-2-yl) D.a-115
3-(pyrid-3-yl) D.a-116 4-(pyrid-3-yl) D.a-117 3-(pyrid-4-yl)
D.a-118 4-(pyrid-4-yl) D.a-119 3-(furan-2-yl) D.a-120
4-(furan-2-yl) D.a-121 3-(furan-3-yl) D.a-122 4-(furan-3-yl)
D.a-123 3-(thien-2-yl) D.a-124 4-(thien-2-yl) D.a-125
3-(thien-3-yl) D.a-126 4-(thien-3-yl) D.b ##STR00029## No.
(R.sup.10).sub.n D.b-1. -- D.b-2. 5-F D.b-3. 4-F D.b-4. 4,5-F.sub.2
D.b-5. 5-Cl D.b-6. 4-Cl D.b-7. 4,5-Cl.sub.2 D.b-8. 3-Br D.b-9. 4-Br
D.b-10. 5-CH.sub.3 D.b-11. 4-CH.sub.3 D.b-12. 4,5-(CH.sub.3).sub.2
D.b-13. 5-CH.sub.2CH.sub.3 D.b-14. 4-CH.sub.2CH.sub.3 D.b-15.
5-CH.sub.2CH.sub.2CH.sub.3 D.b-16. 4-CH.sub.2CH.sub.2CH.sub.3
D.b-17. 5-CH(CH.sub.3).sub.2 D.b-18. 4-CH(CH.sub.3).sub.2 D.b-19.
5-CF.sub.3 D.b-20. 4-CF.sub.3 D.b-21. 5-CHF.sub.2 D.b-22.
4-CHF.sub.2 D.b-23. 5-OH D.b-24. 4-OH D.b-25. 5-OCH.sub.3 D.b-26.
4-OCH.sub.3
D.b-27. 5-CH.sub.2CH.sub.2OCH.sub.3 D.b-28.
4-CH.sub.2CH.sub.2OCH.sub.3 D.b-29. 5-phenyl D.b-30. 4-phenyl
D.b-31. 5-(2- fluorophenyl) D.b-32. 4-(2- fluorophenyl) D.b-33.
5-(3- fluorophenyl) D.b-34. 4-(3- fluorophenyl) D.b-35. 5-(4-
fluorophenyl) D.b-36. 4-(4- fluorophenyl) D.b-37. 5-(2-
chlorophenyl) D.b-38. 4-(2- chlorophenyl) D.b-39. 5-(3-
chlorophenyl) D.b-40. 4-(3- chlorophenyl) D.b-41. 5-(4-
chlorophenyl) D.b-42. 4-(4- chlorophenyl) D.b-43. 5-(2-
bromophenyl) D.b-44. 4-(2- bromophenyl) D.b-45. 5-(3- bromophenyl)
D.b-46. 4-(3- bromophenyl) D.b-47. 5-(4- bromophenyl) D.b-48. 4-(4-
bromophenyl) D.b-49. 5-(2,3- dichlorophenyl) D.b-50. 4-(2,3-
dichlorophenyl) D.b-51. 5-(3,4- dichlorophenyl) D.b-52. 4-(3,4-
dichlorophenyl) D.b-53. 5-(2,4- dichlorophenyl) D.b-54. 4-(2,4-
dichlorophenyl) D.b-55. 5-(2,5- dichlorophenyl) D.b-56. 4-(2,5-
dichlorophenyl) D.b-57. 5-(2-fluoro-6- chlorophenyl) D.b-58.
4-(2-fluoro-6- chlorophenyl) D.b-59. 5-(2,5-dichloro-
3-fluorophenyl) D.b-60. 4-(2,5-dichloro- 3-fluorophenyl) D.b-61.
5-(2- methylphenyl) D.b-62. 4-(2- methylphenyl) D.b-63. 5-(3-
methylphenyl) D.b-64. 4-(3- methylphenyl) D.b-65. 5-(4-
methylphenyl) D.b-66. 4-(4- methylphenyl) D.b-67. 5-(2,3-
dimethylphenyl) D.b-68. 4-(2,3- dimethylphenyl) D.b-69. 5-(2,4-
dimethylphenyl) D.b-70. 4-(2,4- dimethylphenyl) D.b-71. 5-(2,5-
dimethylphenyl) D.b-72. 4-(2,5- dimethylphenyl) D.b-73. 5-(3,5-
dimethylphenyl) D.b-74. 4-(3,5- dimethylphenyl) D.b-75. 5-(2-
isopropyl- phenyl) D.b-76. 4-(2- isopropyl- phenyl) D.b-77. 5-(3-
isopropylphe- nyl) D.b-78. 4-(3-iso- propylphenyl) D.b-79.
5-(4-iso- propylphenyl) D.b-80. 4-(4-iso- propylphenyl) D.b-81.
5-(2-tert- butylphenyl) D.b-82. 4-(2-tert- butylphenyl) D.b-83.
5-(3-tert- butylphenyl) D.b-84. 4-(3-tert- butylphenyl) D.b-85.
5-(4-tert- butylphenyl) D.b-86. 4-(4-tert- butylphenyl) D.b-87.
5-(2- methoxyphenyl) D.b-88. 4-(2-me- thoxyphenyl) D.b-89. 5-(3-me-
hoxyphenyl) D.b-90. 4-(3-me- thoxyphenyl) D.b-91. 5-(4-me-
thoxyphenyl) D.b-92. 4-(4-me- thoxyphenyl) D.b-93. 5-(2,3-dime-
thoxyphenyl) D.b-94. 4-(2,3-dime- thoxyphenyl) D.b-95. 5-(2,4-dime-
thoxyphenyl) D.b-96. 4-(2,4-dime- thoxyphenyl) D.b-97. 5-(2,5-dime-
thoxyphenyl) D.b-98. 4-(2,5-dime- thoxyphenyl) D.b-99. 5-(3,5-dime-
thoxyphenyl) D.b-100. 4-(3,5-dime- thoxyphenyl) D.b-101.
5-(2,3,4-trime- thoxyphenyl) D.b-102. 4-(2,3,4-trime- thoxyphenyl)
D.b-103. 5-(3,4,5-trime- thoxyphenyl) D.b-104. 4-(3,4,5-trime-
thoxyphenyl) D.b-105. 5-(2- ethoxyphenyl) D.b-106. 4-(2-
ethoxyphenyl) D.b-107. 5-(3- ethoxyphenyl) D.b-108. 4-(3-
ethoxyphenyl) D.b-109. 5-(4- ethoxyphenyl) D.b-110. 4-(4-
ethoxyphenyl) D.b-111. 5-(4-benzyl- oxyphenyl) D.b-112.
4-(4-benzyl- xyphenyl) D.b-113. 5-(pyrid-2-yl) D.b-114.
4-(pyrid-2-yl) D.b-115. 5-(pyrid-3-yl) D.b-116. 4-(pyrid-3-yl)
D.b-117. 5-(pyrid-4-yl) D.b-118. 4-(pyrid-4-yl) D.b-119.
5-(furan-2-yl) D.b-120. 4-(furan-2-yl) D.b-121. 5-(furan-3-yl)
D.b-122. 4-(furan-3-yl) D.b-123. 5-(thien-2-yl) D.b-124.
4-(thien-2-yl) D.b-125. 5-(thien-3-yl) D.b-126. 4-(thien-3-yl) D.c
##STR00030## No. D.c-1 -- D.c-2 3-F D.c-3 5-F D.c-4 3,5-F.sub.2
D.c-5 3-Cl D.c-6 5-Cl D.c-7 3,5-Cl.sub.2 D.c-8 3-Br D.c-9 5-Br
D.c-10 3-CH.sub.3 D.c-11 5-CH.sub.3 D.c-12 3,5-(CH.sub.3).sub.2
D.c-13 3-CH.sub.2CH.sub.3 D.c-14 5-CH.sub.2CH.sub.3 D.c-15
3-CH.sub.2CH.sub.2CH.sub.3 D.c-16 5-CH.sub.2CH.sub.2CH.sub.3 D.c-17
3-CH(CH.sub.3).sub.2 D.c-18 5-CH(CH.sub.3).sub.2 D.c-19 3-CF.sub.3
D.c-20 5-CF.sub.3 D.c-21 3-CHF.sub.2 D.c-22 5-CHF.sub.2 D.c-23 3-OH
D.c-24 5-OH D.c-25 3-OCH.sub.3 D.c-26 5-OCH.sub.3 D.c-27
3-CH.sub.2CH.sub.2OCH.sub.3 D.c-28 5-CH.sub.2CH.sub.2OCH.sub.3
D.c-29 3-phenyl D.c-30 5-phenyl D.c-31 3-(2- fluorophenyl) D.c-32
5-(2- fluorophenyl) D.c-33 3-(3- fluorophenyl) D.c-34 5-(3-
fluorophenyl) D.c-35 3-(4- fluorophenyl) D.c-36 5-(4- fluorophenyl)
D.c-37 3-(2- chlorophenyl) D.c-38 5-(2- chlorophenyl) D.c-39 3-(3-
chlorophenyl) D.c-40 5-(3- chlorophenyl) D.c-41 3-(4- chlorophenyl)
D.c-42 5-(4- chlorophenyl) D.c-43 3-(2- bromophenyl) D.c-44 5-(2-
bromophenyl) D.c-45 3-(3- bromophenyl)
D.c-46 5-(3- bromophenyl) D.c-47 3-(4- bromophenyl) D.c-48 5-(4-
bromophenyl) D.c-49 3-(2,3- dichlorophenyl) D.c-50 5-(2,3-
dichlorophenyl) D.c-51 3-(3,4- dichlorophenyl) D.c-52 5-(3,4-
dichlorophenyl) D.c-53 3-(2,4- dichlorophenyl) D.c-54 5-(2,4-
dichlorophenyl) D.c-55 3-(2,5- dichlorophenyl) D.c-56 5-(2,5-
dichlorophenyl) D.c-57 3-(2-fluoro-6- chlorophenyl) D.c-58
5-(2-fluoro-6- chlorophenyl) D.c-59 3-(2,5-dichloro-
3-fluorophenyl) D.c-60 5-(2,5-dichloro- 3-fluorophenyl) D.c-61
3-(2- methylphenyl) D.c-62 5-(2- methylphenyl) D.c-63 3-(3-
methylphenyl) D.c-64 5-(3- methylphenyl) D.c-65 3-(4- methylphenyl)
D.c-66 5-(4- methylphenyl) D.c-67 3-(2,3- dimethylphenyl) D.c-68
5-(2,3- dimethylphenyl) D.c-69 3-(2,4- dimethylphenyl) D.c-70
5-(2,4- dimethylphenyl) D.c-71 3-(2,5- dimethylphenyl) D.c-72
5-(2,5- dimethylphenyl) D.c-73 3-(3,5- dimethylphenyl) D.c-74
5-(3,5- dimethylphenyl) D.c-75 3-(2- isopropyl- phenyl) D.c-76
5-(2- isopropylphe- nyl) D.c-77 3-(3- isopropylphe- nyl) D.c-78
5-(3-iso- propylphenyl) D.c-79 3-(4-iso- propylphenyl) D.c-80
5-(4-iso- propylphenyl) D.c-81 3-(2-tert- butylphenyl) D.c-82
5-(2-tert- butylphenyl) D.c-83 3-(3-tert- butylphenyl) D.c-84
5-(3-tert- butylphenyl) D.c-85 3-(4-tert- butylphenyl) D.c-86
5-(4-tert- butylphenyl) D.c-87 3-(2- methoxyphenyl) D.c-88 5-(2-
methoxyphenyl) D.c-89 3-(3- methoxyphenyl) D.c-90 5-(3-
methoxyphenyl) D.c-91 3-(4- methoxyphenyl) D.c-92 5-(4-
methoxyphenyl) D.c-93 3-(2,3-dime- thoxyphenyl) D.c-94 5-(2,3-dime-
thoxyphenyl) D.c-95 3-(2,4-dime- thoxyphenyl) D.c-96 5-(2,4-dime-
thoxyphenyl) D.c-97 3-(2,5-dime- thoxyphenyl) D.c-98 5-(2,5-dime-
thoxyphenyl) D.c-99 3-(3,5-dime- thoxyphenyl) D.c-100 5-(3,5-dime-
thoxyphenyl) D.c-101 3-(2,3,4-trime- thoxyphenyl) D.c-102
5-(2,3,4-trime- thoxyphenyl) D.c-103 3-(3,4,5-trime- thoxyphenyl)
D.c-104 5-(3,4,5-trime- thoxyphenyl) D.c-105 3-(2- ethoxyphenyl)
D.c-106 5-(2- ethoxyphenyl) D.c-100 3-(3- ethoxyphenyl) D.c-108
5-(3- ethoxyphenyl) D.c-109 3-(4- ethoxyphenyl) D.c-110 5-(4-
ethoxyphenyl) D.c-111 3-(4-benzyl- oxyphenyl) D.c-112 5-(4-benzyl-
oxyphenyl) D.c-113 3-(pyrid-2-yl) D.c-114 5-(pyrid-2-yl) D.c-115
3-(pyrid-3-yl) D.c-116 5-(pyrid-3-yl) D.c-117 3-(pyrid-4-yl)
D.c-118 5-(pyrid-4-yl) D.c-119 3-(furan-2-yl) D.c-120
5-(furan-2-yl) D.c-121 3-(furan-3-yl) D.c-122 5-(furan-3-yl)
D.c-123 3-(thien-2-yl) D.c-124 5-(thien-2-yl) D.c-125
3-(thien-3-yl) D.c-126 5-(thien-3-yl) X = O, S, NR.sup.101
TABLE-US-00005 TABLE E E.a ##STR00031## No. (R.sup.10).sub.n E.a-1.
-- E.a-2. 5-F E.a-3. 4-F E.a-4. 4,5-F.sub.2 E.a-5. 5-Cl E.a-6. 4-Cl
E.a-7. 4,5-Cl.sub.2 E.a-8. 5-Br E.a-9. 4-Br E.a-10. 5-CH.sub.3
E.a-11. 4-CH.sub.3 E.a-12. 4,5-(CH.sub.3).sub.2 E.a-13.
5-CH.sub.2CH.sub.3 E.a-14. 4-CH.sub.2CH.sub.3 E.a-15.
5-CH.sub.2CH.sub.2CH.sub.3 E.a-16. 4-CH.sub.2CH.sub.2CH.sub.3
E.a-17. 5-CH(CH.sub.3).sub.2 E.a-18. 4-CH(CH.sub.3).sub.2 E.a-19.
5-CF.sub.3 E.a-20. 4-CF.sub.3 E.a-21. 5-CHF.sub.2 E.a-22.
4-CHF.sub.2 E.a-23. 5-OH E.a-24. 4-OH E.a-25. 5-OCH.sub.3 E.a-26.
4-OCH.sub.3 E.a-27. 5-CH.sub.2CH.sub.2OCH.sub.3 E.a-28.
4-CH.sub.2CH.sub.2OCH.sub.3 E.a-29. 5-phenyl E.a-30. 4-phenyl
E.a-31. 5-(2- fluorophenyl) E.a-32. 4-(2- fluorophenyl) E.a-33.
5-(3- fluorophenyl) E.a-34. 4-(3- fluorophenyl) E.a-35. 5-(4-
fluorophenyl) E.a-36. 4-(4- fluorophenyl) E.a-37. 5-(2-
chlorophenyl) E.a-38. 4-(2- chlorophenyl) E.a-39. 5-(3-
chlorophenyl) E.a-40. 4-(3- chlorophenyl) E.a-41. 5-(4-
chlorophenyl) E.a-42. 4-(4- chlorophenyl) E.a-43. 5-(2-
bromophenyl) E.a-44. 4-(2- bromophenyl) E.a-45. 5-(3- bromophenyl)
E.a-46. 4-(3- bromophenyl) E.a-47. 5-(4- bromophenyl) E.a-48. 4-(4-
bromophenyl) E.a-49. 5-(2,3- dichlorophenyl) E.a-50. 4-(2,3-
dichlorophenyl) E.a-51. 5-(3,4- dichlorophenyl) E.a-52. 4-(3,4-
dichlorophenyl) E.a-53. 5-(2,4- dichlorophenyl) E.a-54. 4-(2,4-
dichlorophenyl) E.a-55. 5-(2,5- dichlorophenyl) E.a-56. 4-(2,5-
dichlorophenyl) E.a-57. 5-(2-fluoro-6- chlorophenyl) E.a-58.
4-(2-fluoro-6- chlorophenyl) E.a-59. 5-(2,5-dichloro-
3-fluorophenyl) E.a-60. 4-(2,5-dichloro- 3-fluorophenyl) E.a-61.
5-(2- methylphenyl) E.a-62. 4-(2- methylphenyl) E.a-63.
5-(3-methylphenyl) E.a-64. 4-(3-methylphenyl) E.a-65.
5-(4-methylphenyl) E.a-66. 4-(4-methylphenyl) E.a-67.
5-(2,3-dimethylphenyl) E.a-68. 4-(2,3-dimethylphenyl) E.a-69.
5-(2,4-dimelhylphenyl) E.a-70. 4-(2,4-dimethylphenyl) E.a-71.
5-(2,5-dimethylphenyl) E.a-72. 4-(2,5-dimethylphenyl) E.a-73.
5-(3,5-dimethylphenyl) E.a-74. 4-(3,5-dimethylphenyl) E.a-75.
5-(2-isopropylphenyl) E.a-76. 4-(2-isopropylphenyl) E.a-77.
5-(3-isopropylphenyl) E.a-78. 4-(3-iso-propylphenyl) E.a-79.
5-(4-iso-propylphenyl) E.a-80. 4-(4-iso-propylphenyl) E.a-81.
5-(2-tert-butylphenyl) E.a-82. 4-(2-tert- butylphenyl) E.a-83.
5-(3-tert- butylphenyl) E.a-84. 4-(3-tert- butylphenyl) E.a-85.
5-(4-tert- butylphenyl) E.a-86. 4-(4-tert- butylphenyl) E.a-87.
5-(2- methoxyphenyl) E.a-88. 4-(2- methoxyphenyl) E.a-89. 5-(3-
methoxyphenyl) E.a-90. 4-(3- methoxyphenyl) E.a-91. 5-(4-
methoxyphenyl) E.a-92. 4-(4- methoxyphenyl) E.a-93. 5-(2,3-dime-
thoxyphenyl) E.a-94. 4-(2,3-dime- thoxyphenyl) E.a-95. 5-(2,4-dime-
thoxyphenyl) E.a-96. 4-(2,4-dime- thoxyphenyl) E.a-97. 5-(2,5-dime-
thoxyphenyl) E.a-98. 4-(2,5-dime- thoxyphenyl) E.a-99. 5-(3,5-dime-
thoxyphenyl) E.a-100. 4-(3,5-dime- thoxyphenyl) E.a-101.
5-(2,3,4-trime- thoxyphenyl) E.a-102. 4-(2,3,4-trime- thoxyphenyl)
E.a-103. 5-(3,4,5-trime- thoxyphenyl) E.a-104. 4-(3,4,5-trime-
thoxyphenyl) E.a-105. 5-(2- ethoxyphenyl) E.a-106. 4-(2-
ethoxyphenyl) E.a-107. 5-(3- ethoxyphenyl) E.a-108. 4-(3-
ethoxyphenyl) E.a-109. 5-(4- ethoxyphenyl) E.a-110. 4-(4-
ethoxyphenyl) E.a-111. 5-(4-benzyl- oxyphenyl) E.a-112.
4-(4-benzyl- oxyphenyl) E.a-113. 5-(pyrid-2-yl) E.a-114.
4-(pyrid-2-yl) E.a-115. 5-(pyrid-3-yl) E.a-116. 4-(pyrid-3-yl)
E.a-117. 5-(pyrid-4-yl) E.a-118. 4-(pyrid-4-yl) E.a-119.
5-(furan-2-yl) E.a-120. 4-(furan-2-yl) E.a-121. 5-(furan-3-yl)
E.a-122. 4-(furan-3-yl) E.a-123. 5-(thien-2-yl) E.a-124.
4-(thien-2-yl) E.a-125. 5-(thien-3-yl) E.a-126. 4-(thien-3-yl) E.b
##STR00032## No. (R.sup.10).sub.n E.b-1. -- E.b-2. 5-F E.b-3. 2-F
E.b-4. 2,5-F.sub.2 E.b-5. 5-Cl E.b-6. 2-Cl E.b-7. 2,5-Cl.sub.2
E.b-8. 5-Br E.b-9. 2-Br E.b-10. 5-CH.sub.3 E.b-11. 2-CH.sub.3
E.b-12. 2,5-(CH.sub.3).sub.2 E.b-13. 5-CH.sub.2CH.sub.3 E.b-14.
2-CH.sub.2CH.sub.3 E.b-15. 5-CH.sub.2CH.sub.2CH.sub.3 E.b-16.
2-CH.sub.2CH.sub.2CH.sub.3 E.b-17. 5-CH(CH.sub.3).sub.2 E.b-18.
2-CH(CH.sub.3).sub.2 E.b-19. 5-CF.sub.3 E.b-20. 2-CF.sub.3 E.b-21.
5-CHF.sub.2 E.b-22. 2-CHF.sub.2 E.b-23. 5-OH E.b-24. 2-OH E.b-25.
5-OCH.sub.3 E.b-26. 2-OCH.sub.3 E.b-27. 5-CH.sub.2CH.sub.2OCH.sub.3
E.b-28. 2-CH.sub.2CH.sub.2OCH.sub.3 E.b-29. 5-phenyl E.b-30.
2-phenyl E.b-31. 5-(2- fluorophenyl) E.b-32. 2-(2- fluorophenyl)
E.b-33. 5-(3- fluorophenyl) E.b-34. 2-(3- fluorophenyl) E.b-35.
5-(4- fluorophenyl) E.b-36. 2-(4- fluorophenyl) E.b-37. 5-(2-
chlorophenyl) E.b-38. 2-(2- chlorophenyl) E.b-39. 5-(3-
chlorophenyl)
E.b-40. 2-(3- chlorophenyl) E.b-41. 5-(4- chlorophenyl) E.b-42.
2-(4- chlorophenyl) E.b-43. 5-(2- bromophenyl) E.b-44. 2-(2-
bromophenyl) E.b-45. 5-(3- bromophenyl) E.b-46. 2-(3- bromophenyl)
E.b-47. 5-(4- bromophenyl) E.b-48. 2-(4- bromophenyl) E.b-49.
5-(2,3- dichlorophenyl) E.b-50. 2-(2,3- dichlorophenyl) E.b-51.
5-(3,4- dichlorophenyl) E.b-52. 2-(3,4- dichlorophenyl) E.b-53.
5-(2,4- dichlorophenyl) E.b-54. 2-(2,4- dichlorophenyl) E.b-55.
5-(2,5- dichlorophenyl) E.b-56. 2-(2,5- dichlorophenyl) E.b-57.
5-(2-fluoro-6- chlorophenyl) E.b-58. 2-(2-fluoro-6- chlorophenyl)
E.b-59. 5-(2,5-dichloro- 3-fluorophenyl) E.b-60. 2-(2,5-dichloro-
3-fluorophenyl) E.b-61. 5-(2- methylphenyl) E.b-62. 2-(2-
methylphenyl) E.b-63. 5-(3-methylphenyl) E.b-64. 2-(3-methylphenyl)
E.b-65. 5-(4-methylphenyl) E.b-66. 4-(4-methylphenyl) E.b-67.
5-(2,3-dimethylphenyl) E.b-68. 2-(2,3-dimethylphenyl) E.b-69.
5-(2,4-dimethylphenyl) E.b-70. 2-(2,4-dimethylphenyl) E.b-71.
5-(2,5-dimethylphenyl) E.b-72. 2-(2,5-dimethylphenyl) E.b-73.
5-(3,5-dimethylphenyl) E.b-74. 2-(3,5-dimethylphenyl) E.b-75.
5-(2-isopropylphenyl) E.b-76. 2-(2-isopropylphenyl) E.b-77.
5-(3-isopropylphenyl) E.b-78. 2-(3-iso-propylphenyl) E.b-79.
5-(4-iso-propylphenyl) E.b-80. 2-(4-iso-propylphenyl) E.b-81.
5-(2-tert-butylphenyl) E.b-82. 2-(2-tert- butylphenyl) E.b-83.
5-(3-tert- butylphenyl) E.b-84. 2-(3-tert- butylphenyl) E.b-85.
5-(4-tert- butylphenyl) E.b-86. 2-(4-tert- butylphenyl) E.b-87.
5-(2- methoxyphenyl) E.b-88. 2-(2- methoxyphenyl) E.b-89. 5-(3-
methoxyphenyl) E.b-90. 2-(3- methoxyphenyl) E.b-91. 5-(4-
methoxyphenyl) E.b-92. 2-(4- methoxyphenyl) E.b-93. 5-(2,3-dime-
thoxyphenyl) E.b-94. 2-(2,3-dime- thoxyphenyl) E.b-95. 5-(2,4-dime-
thoxyphenyl) E.b-96. 2-(2,4-dime- thoxyphenyl) E.b-97. 5-(2,5-dime-
thoxyphenyl) E.b-98. 2-(2,5-dime- thoxyphenyl) E.b-99. 5-(3,5-dime-
thoxyphenyl) E.b-100. 2-(3,5-dime- thoxyphenyl) E.b-101.
5-(2,3,4-trime- thoxyphenyl) E.b-102. 2-(2,3,4-trime- thoxyphenyl)
E.b-103. 5-(3,4,5-trime- thoxyphenyl) E.b-104. 2-(3,4,5-trime-
thoxyphenyl) E.b-105. 5-(2- ethoxyphenyl) E.b-106. 2-(2-
ethoxyphenyl) E.b-107. 5-(3- ethoxyphenyl) E.b-108. 2-(3-
ethoxyphenyl) E.b-109. 5-(4- ethoxyphenyl) E.b-110. 2-(4-
ethoxyphenyl) E.b-111. 5-(4-benzyl- oxyphenyl) E.b-112.
24-(4-benzyl- oxyphenyl) E.b-113. 5-(pyrid-2-yl) E.b-114.
2-(pyrid-2-yl) E.b-115. 5-(pyrid-3-yl) E.b-116. 2-(pyrid-3-yl)
E.b-117. 5-(pyrid-4-yl) E.b-118. 2-(pyrid-4-yl) E.b-119.
5-(furan-2-yl) E.b-120. 2-(furan-2-yl) E.b-121. 5-(furan-3-yl)
E.b-122. 2-(furan-3-yl) E.b-123. 5-(thien-2-yl) E.b-124.
2-(thien-2-yl) E.b-125. 5-(thien-3-yl) E.b-126. 2-(thien-3-yl) E.c
##STR00033## No. (R.sup.10).sub.n E.c-1. -- E.c-2. 2-F E.c-3. 4-F
E.c-4. 2,4-F.sub.2 E.c-5. 2-Cl E.c-6. 4-Cl E.c-7. 2,4-Cl.sub.2
E.c-8. 2-Br E.c-9. 4-Br E.c-10. 2-CH.sub.3 E.c-11. 4-CH.sub.3
E.c-12. 2,4-(CH.sub.3).sub.2 E.c-13. 2-CH.sub.2CH.sub.3 E.c-14.
4-CH.sub.2CH.sub.3 E.c-15. 2-CH.sub.2CH.sub.2CH.sub.3 E.c-16.
4-CH.sub.2CH.sub.2CH.sub.3 E.c-17. 2-CH(CH.sub.3).sub.2 E.c-18.
4-CH(CH.sub.3).sub.2 E.c-19. 2-CF.sub.3 E.c-20. 4-CF.sub.3 E.c-21.
2-CHF.sub.2 E.c-22. 4-CHF.sub.2 E.c-23. 2-OH E.c-24. 4-OH E.c-25.
2-OCH.sub.3 E.c-26. 4-OCH.sub.3 E.c-27. 2-CH.sub.2CH.sub.2OCH.sub.3
E.c-28. 4-CH.sub.2CH.sub.2OCH.sub.3 E.c-29. 2-phenyl E.c-30.
4-phenyl E.c-31. 2-(2-fluorophenyl) E.c-32. 4-(2-fluorophenyl)
E.c-33. 2-(3-fluorophenyl) E.c-34. 4-(3-fluorophenyl) E.c-35.
2-(4-fluorophenyl) E.c-36. 4-(4-fluorophenyl) E.c-37.
2-(2-chlorophenyl) E.c-38. 4-(2-chlorophenyl) E.c-39.
2-(3-chlorophenyl) E.c-40. 4-(3-chlorophenyl) E.c-41.
2-(4-chlorophenyl) E.c-42. 4-(4-chlorophenyl) E.c-43.
2-(2-bromophenyl) E.c-44. 4-(2-bromophenyl) E.c-45.
2-(3-bromophenyl) E.c-46. 4-(3-bromophenyl) E.c-47.
2-(4-bromophenyl) E.c-48. 4-(4-bromophenyl) E.c-49. 2-(2,3-
dichlorophenyl) E.c-50. 4-(2,3- dichlorophenyl) E.c-51. 2-(3,4-
dichlorophenyl) E.c-52. 4-(3,4- dichlorophenyl) E.c-53. 2-(2,4-
dichlorophenyl) E.c-54. 4-(2,4- dichlorophenyl) E.c-55. 2-(2,5-
dichlorophenyl) E.c-56. 4-(2,5- dichlorophenyl) E.c-57.
2-(2-fluoro-6- chlorophenyl) E.c-58. 4-(2-fluoro-6- chlorophenyl)
E.c-59. 2-(2,5-dichloro-3- fluorophenyl) E.c-60. 4-(2,5-dichloro-3-
fluorophenyl) E.c-61. 2-(2- methylphenyl) E.c-62. 4-(2-
methylphenyl) E.c-63. 2-(3-methylphenyl) E.c-64. 4-(3-methylphenyl)
E.c-65. 2-(4-methylphenyl) E.c-66. 4-(4-methylphenyl) E.c-67.
2-(2,3-dimelhylphenyl) E.c-68. 4-(2,3-dimethylphenyl) E.c-69.
2-(2.4-dimelhylphenyl) E.c-70. 4-(2,4-dimethylphenyl) E.c-71.
2-(2,5-dimelhylphenyl) E.c-72. 4-(2,5-dimethylphenyl) E.c-73.
2-(3,5-dimethylphenyl) E.c-74. 4-(3,5-dimethylphenyl) E.c-75.
2-(2-isopropylphenyl) E.c-76. 4-(2-isopropylphenyl) E.c-77.
2-(3-isopropylphenyl) E.c-78. 4-(3-iso-propylphenyl) E.c-79.
2-(4-iso-propylphenyl) E.c-80. 4-(4-iso-propylphenyl) E.c-81.
2-(2-tert-butylphenyl) E.c-82. 4-(2-tert- butylphenyl) E.c-83.
2-(3-tert- butylphenyl) E.c-84. 4-(3-tert- butylphenyl) E.c-85.
2-(4-tert- butylphenyl) E.c-86. 4-(4-tert-
butylphenyl) E.c-87. 2-(2- methoxyphenyl) E.c-88. 4-(2-
methoxyphenyl) E.c-89. 2-(3- methoxyphenyl) E.c-90. 4-(3-
methoxyphenyl) E.c-91. 2-(4- methoxyphenyl) E.c-92. 4-(4-
methoxyphenyl) E.c-93. 2-(2,3-dime- thoxyphenyl) E.c-94.
4-(2,3-dime- thoxyphenyl) E.c-95. 2-(2,4-dime- thoxyphenyl) E.c-96.
4-(2,4-dime- thoxyphenyl) E.c-97. 2-(2,5-dime- thoxyphenyl) E.c-98.
4-(2,5-dime- thoxyphenyl) E.c-99. 2-(3,5-dime- thoxyphenyl)
E.c-100. 4-(3,5-dime- thoxyphenyl) E.c-101. 2-(2,3,4-trime-
thoxyphenyl) E.c-102. 4-(2,3,4-trime- thoxyphenyl) E.c-103.
2-(3,4,5-trime- thoxyphenyl) E.c-104. 4-(3,4,5-trime- thoxyphenyl)
E.c-105. 2-(2- ethoxyphenyl) E.c-106. 4-(2- ethoxyphenyl) E.c-107.
2-(3- ethoxyphenyl) E.c-108. 4-(3- ethoxyphenyl) E.c-109. 2-(4-
ethoxyphenyl) E.c-110. 4-(4- ethoxyphenyl) E.c-111. 2-(4-benzyl-
oxyphenyl) E.c-112. 4-(4-benzyl- oxyphenyl) E.c-113. 2-(pyrid-2-yl)
E.c-114. 4-(pyrid-2-yl) E.c-115. 2-(pyrid-3-yl) E.c-116.
4-(pyrid-3-yl) E.c-117. 2-(pyrid-4-yl) E.c-118. 4-(pyrid-4-yl)
E.c-119. 2-(furan-2-yl) E.c-120. 4-(furan-2-yl) E.c-121.
2-(furan-3-yl) E.c-122. 4-(furan-3-yl) E.c-123. 2-(thien-2-yl)
E.c-124. 4-(thien-2-yl) E.c-125. 2-(thien-3-yl) E.c-126.
4-(thien-3-yl) X = O, S, NR.sup.101
TABLE-US-00006 TABLE F No. R.sup.10 F-1. -- F-2. F F-3. Cl F-4. Br
F-5. CH.sub.3 F-6. CH.sub.2CH.sub.3 F-7. CH.sub.2CH.sub.2CH.sub.3
F-8. CH(CH.sub.3).sub.2 F-9. CF.sub.3 F-10. CHF.sub.2 F-11. OH
F-12. OCH.sub.3 F-13. CH.sub.2CH.sub.2OCH.sub.3 F-14. phenyl F-15.
2-fluorophenyl F-16. 3-fluorophenyl F-17. 4-fluorophenyl F-18.
2-chlorophenyl F-19. 3-chlorophenyl F-20. 4-chlorophenyl F-21.
2-bromophenyl F-22. 3-bromophenyl F-23. 4-bromophenyl F-24.
2,3-dichlorophenyl F-25. 3,4-dichlorophenyl F-26.
2,4-dichlorophenyl F-27. 2,5-dichlorophenyl F-28.
2-fluoro-6-chlorophenyl F-29. 2,5-dichloro-3-fluorophenyl F-30.
2-methylphenyl F-31. 3-methylphenyl F-32. 4-methylphenyl F-33.
2,3-dimethylphenyl F-34. 2,4-dimethylphenyl F-35.
2,5-dimethylphenyl F-36. 3,5-dimethylphenyl F-37. 2-isopropylphenyl
F-38. 3-isopropylphenyl F-39. 4-isopropylphenyl F-40.
2-tert-butylphenyl F-41. 3-tert-butylphenyl F-42.
4-tert-butylphenyl F-43. 2-methoxyphenyl F-44. 3-methoxyphenyl
F-45. 4-methoxyphenyl F-46. 2,3-dimethoxyphenyl F-47.
2,4-dimethoxyphenyl F-48. 2,5-dimethoxyphenyl F-49.
3,5-dimethoxyphenyl F-50. 2,3,4-trimethoxyphenyl F-51.
3,4,5-trimethoxyphenyl F-52. 2-ethoxyphenyl F-53. 3-ethoxyphenyl
F-54. 4-ethoxyphenyl F-55. 4-benzyloxyphenyl F-56. pyrid-2-yl F-57.
pyrid-3-yl F-58. pyrid-4-yl F-59. furan-2-yl F-60. furan-3-yl F-61.
thien-2-yl F-62. thien-3-yl
TABLE-US-00007 TABLE G ##STR00034## ##STR00035## ##STR00036##
##STR00037## ##STR00038## ##STR00039## ##STR00040## ##STR00041##
No. (R.sup.10).sub.n G-1. -- G-2. 1-F G-3. 2-F G-4. 3-F G-5. 4-F
G-6. 5-F G-7. 6-F G-8. 7-F G-9. 8-F G-10. 1-Cl G-11. 2-Cl G-12.
3-Cl G-13. 4-Cl G-14. 5-Cl G-15. 6-Cl G-16. 7-Cl G-17. 8-Cl G-18.
1-Br G-19. 2-Br G-20. 3-Br G-21. 4-Br G-22. 5-Br G-23. 6-Br G-24.
7-Br G-25. 8-Br G-26. 1-OH G-27. 2-OH G-28. 3-OH G-29. 4-OH G-30.
5-OH G-31. 6-OH G-32. 7-OH G-33. 8-OH G-34. 1-CH.sub.3 G-35.
2-CH.sub.3 G-36. 3-CH.sub.3 G-37. 4-CH.sub.3 G-38. 5-CH.sub.3 G-39.
6-CH.sub.3 G-40. 7-CH.sub.3 G-41. 8-CH.sub.3 G-42.
3,5-(CH.sub.3).sub.2 G-43. 3,6-(CH.sub.3).sub.2 G-44.
3,7-(CH.sub.3).sub.2 G-45. 3,8-(CH.sub.3).sub.2 G-46.
4,5-(CH.sub.3).sub.2 G-47. 4,6-(CH.sub.3).sub.2 G-48.
4,7-(CH.sub.3).sub.2 G-49. 4,8-(CH.sub.3).sub.2 G-50. 1-OCH.sub.3
G-51. 2-OCH.sub.3 G-52. 3-OCH.sub.3 G-53. 4-OCH.sub.3 G-54.
5-OCH.sub.3 G-55. 6-OCH.sub.3 G-56. 7-OCH.sub.3 G-57. 8-OCH.sub.3
G-58. 3,5-(OCH.sub.3).sub.2 G-59. 3,6-(OCH.sub.3).sub.2 G-60.
3,7-(OCH.sub.3).sub.2 G-61. 3,8-(OCH.sub.3).sub.2 G-62.
4,5-(OCH.sub.3).sub.2 G-63. 4,6-(OCH.sub.3).sub.2 G-64.
4,7-(OCH.sub.3).sub.2 G-65. 4,8-(OCH.sub.3).sub.2 G-66. 1-NHCHO
G-67. 2-NHCHO G-68. 3-NHCHO G-69. 4-NHCHO G-70. 5-NHCHO G-71.
6-NHCHO G-72. 7-NHCHO G-73. 8-NHCHO X = O, S, NR.sup.101; Y = CH,
N
TABLE-US-00008 TABLE H No. R.sup.101 H-1. H H-2. CH.sub.3 H-3.
CH.sub.2CH.sub.3 H-4. CH.sub.2CH.sub.2CH.sub.3 H-5.
CH(CH.sub.3).sub.2 H-6. CHF.sub.2 H-7. CH.sub.2CH.sub.2OCH.sub.3
H-8. CH.sub.2CH.sub.2CH.sub.2OCH.sub.3 H-9. cyclohexyl H-10.
C(O)O--C(CH.sub.3).sub.3 H-11. phenyl H-12. 2-fluorophenyl H-13.
3-fluorophenyl H-14. 4-fluorophenyl H-15. 2-methoxyphenyl H-16.
3-methoxyphenyl H-17. 4-methoxyphenyl H-18. 2-pyridyl H-19.
3-pyridyl H-20. 4-pyridyl
[0688] Compounds I of the present invention can be synthesized as
outlined in the synthetic routes shown below.
##STR00042##
(A=OH, O--C(O)--R, OR, 1-imidazolyl, 1-pyrazolyl or Cl; R.sup.7',
R.sup.8' and R.sup.9' are R.sup.7, R.sup.8 and R.sup.9 or
precursors of these groups)
[0689] A precursor is a radical which can be easily removed and
replaced by the desired group or which can be modified to give the
desired group. The precursor can also be an N-protective group.
[0690] As shown in scheme 1, compounds of formula I or precursors
thereof can be prepared from the acid (derivative) II and the amine
III by standard amide bond forming reactions. In case A is Cl, the
reaction needs no further activation.
[0691] When the carboxylic acid II (A=OH) itself is used as the
reactant II, the reaction is advantageously carried out in the
presence of a coupling reagent. Suitable coupling reagents
(activators) are known to those skilled in the art and are
selected, for example, from carbodiimides such as DCC
(dicyclohexylcarbodiimide), EDC (1-ethyl-3-(dimethylamino)-propyl)
carbodiimide), CDI (carbonyldiimidazole), carbonyldipyrazole and
DCI (diisopropylcarbodiimide), benzotriazole derivatives such as
1-hydroxybenzotriazole, HBTU
((O-benzotriazol-1-yl)-N,N',N'-tetramethyluronium
hexafluorophosphate) and HCTU
(1-[bis(dimethylamino)methylene]-5-chloro-1Hbenzotriazolium
tetrafluoroborate), pyridinotriazole derivatives such HATU
(2-(7-aza-1H-bentotriazol-1-yl)-1,1,3,3-tetramethyluronium
hexafluorophosphate), and phosphonium activators such as BOP
((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium
hexafluorophosphate), Py-BOP
((benzotriazol-1-yloxy)tripyrrolidinephosphonium
hexafluorophosphate) and Py-BrOP (bromotripyrrolidinephosphonium
hexafluorophosphate). In general, the activator is used in excess.
The benzotriazole and phosphonium coupling reagents are generally
used in a basic medium, e.g. in the presence of an amine different
from III, preferably a non-nucleophilic amine, such as tertiary
aliphatic and alicyclic amines.
[0692] The acid anhydride II (A=--O--C(O)--R) is an asymmetric
anhydride in which --O--C(O)--R is a group which can be displaced
easily by the amine III used in the reaction. Suitable acid
derivatives with which the carboxylic acid II (A=OH) forms suitable
mixed anhydrides are, for example, the esters of chloroformic acid,
for example isopropyl chloroformate and isobutyl chloroformate.
[0693] Suitable esters II (A=OR) derive preferably from
C.sub.1-C.sub.4-alkanols ROH in which R is C.sub.1-C.sub.4-alkyl,
such as methanol, ethanol, propanol, isopropanol, n-butanol,
butan-2-ol, isobutanol and tert-butanol, preference being given to
the methyl and ethyl esters (R=methyl or ethyl). Suitable esters
may also derive from C.sub.2-C.sub.6-polyols such as glycol,
glycerol, trimethylolpropane, erythritol, pentaerythritol and
sorbitol, preference being given to the glycerol ester.
[0694] Alternatively, as ester II (A=OR) can be used a so-called
active ester, which is obtained by the reaction of the acid II
(A=OH) with an active ester-forming alcohol such as p-nitrophenol,
N-hydroxysuccinimide or OPfp (pentafluorophenol).
[0695] In a further alternative, A is 1-imidazolyl, i.e. the
compound II is an amide with imidazole as amine component, or A is
1-pyrazolyl, i.e. the compound II is an amide with pyrazole as
amine component. This compound can be obtained by reacting the
corresponding acid chloride (compound II wherein A=Cl) with
imidazole or pyrazole, respectively or, more suitably, it is formed
as an intermediate when the acid (compound II with A=OH) is reacted
with CDI or with carbonyldipyrazole.
##STR00043##
(R.sup.7', R.sup.8' and R.sup.9' are R.sup.7, R.sup.8 and R.sup.9
or precursors of these groups)
[0696] Alternatively, the amide IV can be coupled to a pyridine
through a variety of metalmediated coupling reactions well known to
those skilled in the art. For example, the amide IV can be coupled
with a 4-pyridyl tin reagent (Stille reaction) or with a 4-pyridyl
boronic acid (Suzuki coupling) in the presence of a palladium
catalyst. These reaction types and suitable reaction conditions are
well known in the art.
[0697] 4-(Pyrid-4-yl)-benzoic acids II (A=OH) are commercially
available or can be prepared by known substitution reactions on
aromaticsheteroaromatics from commercially available compounds.
Acid derivatives (A=Cl; OR; OC(O)R) can be prepared ba standard
derivatization reactions, for example by reaction of the acid with
sulfonyl chloride to give the chloride (A=Cl), by reaction of the
acid or the chloride with an alcohol ROH to give an ester (A=OR) or
by reaction of the acid or the chloride with an acid RCOOH to give
an anhydride (A=OC(O)R).
[0698] Amines III are commercially available or can be prepared by
standard alkylation, arylation, acylation or sulfonation reactions
of amines.
[0699] 4-Bromobenzoic amides IV are commercially available or can
be prepared by amide bond formation from the corresponding
4-bromobenzoic acid or an acid derivative thereof and an amine III
in analogy to the method described with respect to scheme 1.
[0700] If R.sup.7', R.sup.8' and R.sup.9' in compound I' are not
the desired final groups R.sup.7, R.sup.8 and R.sup.9, they can be
converted into these by standard methods. For example, if R.sup.7'
represents H, this can be converted into a group R.sup.7 different
from H by alkylating or arylating the amido nitrogen atom. R.sup.7'
can also be a protective group. The protective group may be removed
to yield a compound I wherein R.sup.7' is H. Suitable protective
groups are known in the art and are, for example, selected from
tert-butoxycarbonyl (boc), benzyloxycarbonyl (Cbz),
9-fluorenylmethoxycarbonyl (Fmoc), triphenylmethyl (Trt) and
nitrobenzenesulfenyl (Nps). A preferred protective group is boc.
The protective groups can be removed by known methods, such as
treatment of the protected amine with an acid, e.g halogen acid,
such as HCl or HBr, or trifluoroacetic acid, or by hydrogenation,
optionally in the presence of a Pd catalyst. The resulting
compound, wherein R.sup.7' is H, can then be reacted, as already
said, in the sense of an alkylation, with a compound R.sup.7--X. In
this compound, R.sup.7 is C.sub.1-C.sub.8-alkyl,
C.sub.1-C.sub.8-haloalkyl, C.sub.6-C.sub.14-aryl or
C.sub.6-C.sub.14-aryl-C.sub.1-C.sub.4-alkyl and X is a
nucleophilically displaceable leaving group, e.g. halogen,
trifluoroacetate, alkylsulfonate, arylsulfonate, alkyl sulfate and
the like. The reaction conditions which are required for the
alkylation have been adequately disclosed, e.g. in Bioorganic and
Medicinal Chemistry Lett. 2002, 12(7), pp. 2443-2446 and also 2002,
12(5), pp. 1917-1919.
[0701] If R.sup.8 is a group X--W', where W' does not carry the
desired substituent R.sup.10, this can be converted into the
desired radical by standard substitution reactions. In particular
N-bound radicals R.sup.10 can be introduced into compounds of the
formula I by reacting the corresponding halogen compound, i.e. a
compound of the formula I, which instead of the desired group
R.sup.10 carries a halogen atom, in particular a bromine or iodine
atom, with a primary or secondary amine in the presence of a base,
preferably also in the presence of a palladium catalyst in terms of
a Buchwald-Hartwig reaction.
[0702] If R.sup.9 is a group Y'--CH.sub.2OH (Y'=single bond, CO,
C.sub.1-C.sub.3-alkylene), this can for example be converted into a
group Y'--CH.sub.2NR.sup.12R.sup.13 by first oxidizing the alcohol
group to a carbonyl function (Y'--CHO) and the submitting the
resulting aldehyde to a reductive amination with an amine
NHR.sup.12R.sup.13. Suitable reductive agents are for example
borohydrides such as sodium borohydride, sodium cyanoborohydride or
sodium triacetoxyborohydride. The skilled person is familiar with
the reaction conditions which are required for a reductive
amination, e.g. from Bioorganic and Medicinal Chemistry Lett. 2002,
12(5), pp. 795-798 and 12(7) pp. 1269-1273.
[0703] By starting from enantiomerically pure (S)- or pure
(R)-amines III, enantiomerically pure (S)- and (R)-enantiomers of
compounds I (with respect to the configuration at the C(H)atom
bound to NR.sup.7) can be obtained. Alternatively, racemates of
compounds I, I' or IV can be separated, e.g. by chromatography
using a chiral stationary phase.
[0704] If not indicated otherwise, the above-described reactions
are generally carried out in a solvent at temperatures between room
temperature and the boiling temperature of the solvent employed.
Alternatively, the activation energy which is required for the
reaction can be introduced into the reaction mixture using
microwaves, something which has proved to be of value, in
particular, in the case of the reactions catalyzed by transition
metals (with regard to reactions using microwaves, see Tetrahedron
2001, 57, p. 9199 ff. p. 9225 if. and also, in a general manner,
"Microwaves in Organic Synthesis", Andre Loupy (Ed.), Wiley-VCH
2002.
[0705] The acid addition salts of compounds I are prepared in a
customary manner by mixing the free base with a corresponding acid,
where appropriate in solution in an organic solvent, for example a
lower alcohol, such as methanol, ethanol or propanol, an ether,
such as methyl tert-butyl ether or diisopropyl ether, a ketone,
such as acetone or methyl ethyl ketone, or an ester, such as ethyl
acetate.
[0706] The compounds according to the invention of the formula I
have a surprisingly high affinity for ROCK1 and ROCK2.
Specifically, they have a ROCK antagonistic activity.
[0707] The high activity of the compounds according to the
invention for ROCKs is reflected in very low in-vitro enzyme
inhibition constants (K.sub.i(ROCK) values) of as a rule less than
500 nM (nmol/l), preferably of less than 100 nM and, in particular
of less than 50 nM. The modulation of phosphorylation of suitable
peptide substrates can, for example, be used in studies for
determining enzyme inhibition constants of ROCK.
[0708] Because of their profile, the compounds can be used for
treating diseases which respond to the influencing of ROCK
activity, i.e. they are effective for treating those medical
disorders or diseases in which exerting an influence on
(modulating) the ROCK activity leads to an improvement in the
clinical picture or to the disease being cured. Examples of these
diseases are given above.
[0709] The disorders which can be treated in accordance with the
invention include the diseases listed in the introductory part,
e.g. cardiovascular diseases such as hypertension, chronic and
congestive heart failure, cardiac hypertrophy, chronic renal
failure, cerebral vasospasm after subarachnoid bleeding, pulmonary
hypertension and ocular hypertension, cancer and tumor metastasis,
asthma, male erectile dysfunctions, female sexual dysfunctions,
over-active bladder syndrome, preterm labor, ischemia reperfusion,
myocardial infarction, restenosis, atherosclerosis, graft failure,
CNS disorders, such acute neuronal injury, e.g. spinal chord
injury, traumatic brain injury and stroke, Parkinson's disease and
Alzheimer's disease, inflammatory and demyelating diseases such as
multiple sclerosis, acute and chronic pain, rheumatoid arthritis,
osteoarthritis, osteoporosis, irritable bowel syndrome and
inflammatory bowel disease, amyotrophic lateral sclerosis, HIV-1
encephalitis, virus and bacterial infections, insulin resistance,
diabetes, cognitive dysfunctions, such as the above-mentioned
Alzheimer disease, vascular dementia and other dementia forms,
glaucoma, psoriasis, retinopathy, and benign prostatic hypertrophy.
In particular the disorders are cancer, pain, asthma, cognitive
dysfunctions, in particular vascular dementia and Alzheimer's
disease, multiple sclerosis, rheumatoid arthritis and spinal cord
injuries.
[0710] Within the meaning of the invention, a treatment also
includes a preventive treatment (prophylaxis), in particular as
relapse prophylaxis or phase prophylaxis, as well as the treatment
of acute or chronic signs, symptoms and/or malfunctions. The
treatment can be orientated symptomatically, for example as the
suppression of symptoms. It can be effected over a short period, be
orientated over the medium term or can be a long-term treatment,
for example within the context of a maintenance therapy.
[0711] Within the context of the treatment, the use according to
the invention of the described compounds involves a method. In this
method, an effective quantity of one or more compounds, as a rule
formulated in accordance with pharmaceutical and veterinary
practice, is administered to the individual to be treated,
preferably a mammal, in particular a human being, productive animal
or domestic animal. Whether such a treatment is indicated, and in
which form it is to take place, depends on the individual case and
is subject to medical assessment (diagnosis) which takes into
consideration signs, symptoms and/or malfunctions which are
present, the risks of developing particular signs, symptoms and/or
malfunctions, and other factors.
[0712] As a rule, the treatment is effected by means of single or
repeated daily administration, where appropriate together, or
alternating, with other active compounds or active
compound-containing preparations such that a daily dose of
preferably from about 0.1 to 1000 mg/kg of bodyweight, in the case
of oral administration, or of from about 0.1 to 100 mg/kg of
bodyweight, in the case of parenteral administration, is supplied
to an individual to be treated.
[0713] If desired, the effective daily dose can be divided into
multiple doses for purposes of administration. Consequently, single
dose compositions may contain such amounts or submultiples thereof
to make up the daily dose.
[0714] The invention also relates to the production of
pharmaceutical compositions for treating an individual, preferably
a mammal, in particular a human being, productive animal or
domestic animal. Thus, the ligands are customarily administered in
the form of pharmaceutical compositions which comprise a
pharmaceutically acceptable excipient together with at least one
compound according to the invention and, where appropriate, other
active compounds. These compositions can, for example, be
administered orally, rectally, transdermally, subcutaneously,
intravenously, intramuscularly or intranasally.
[0715] Examples of suitable pharmaceutical formulations are solid
medicinal forms, such as powders, granules, tablets, in particular
film tablets, lozenges, sachets, cachets, sugarcoated tablets,
capsules, such as hard gelatin capsules and soft gelatin capsules,
suppositories or vaginal medicinal forms, semisolid medicinal
forms, such as ointments, creams, hydrogels, pastes or plasters,
and also liquid medicinal forms, such as solutions, emulsions, in
particular oil-in-water emulsions, suspensions, for example
lotions, injection preparations and infusion preparations, and
eyedrops and eardrops. Implanted release devices can also be used
for administering inhibitors according to the invention. In
addition, it is also possible to use liposomes or microspheres.
[0716] When producing the compositions, the compounds according to
the invention are optionally mixed or diluted with one or more
excipients. Excipients can be solid, semisolid or liquid materials
which serve as vehicles, carriers or medium for the active
compound.
[0717] Suitable excipients are listed in the specialist medicinal
monographs. In addition, the formulations can comprise
pharmaceutically acceptable carriers or customary auxiliary
substances, such as glidants; wetting agents; emulsifying and
suspending agents; preservatives; antioxidants; antiirritants;
chelating agents; coating auxiliaries; emulsion stabilizers; film
formers; gel formers; odor masking agents; taste corrigents; resin;
hydrocolloids; solvents; solubilizers; neutralizing agents;
diffusion accelerators; pigments; quaternary ammonium compounds;
refatting and overfatting agents; raw materials for ointments,
creams or oils; silicone derivatives; spreading auxiliaries;
stabilizers; sterilants; suppository bases; tablet auxiliaries,
such as binders, fillers, glidants, disintegrants or coatings;
propellants; drying agents; opacifiers; thickeners; waxes;
plasticizers and white mineral oils. A formulation in this regard
is based on specialist knowledge as described, for example, in
Fiedler, H. P., Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik and
angrenzende Gebiete [Encyclopedia of auxiliary substances for
pharmacy, cosmetics and related fields], .sup.4th edition,
Aulendorf: ECV-Editio-Kantor-Verlag, 1996.
[0718] The following examples serve to explain the invention
without limiting it.
Experimental Part:
ABBREVIATIONS USED
[0719] DCM dichloromethane [0720] DEA diethylamine [0721] DIEA
diisopropylethyl amine [0722] DMA N,N-dimethylacetamide [0723] DMF
N,N-dimethylformamide [0724] DMSO dimethyl sulfoxide [0725] EDC
1-ethyl-3-(dimethylamino)-propyl)carbodiimide [0726] EtOAc ethyl
acetate [0727] EtOH ethanol [0728] HATU
O-(7-azabenzotriazole-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate [0729] HOBT N-hydroxybenzotriazole [0730] MeOH
methanol [0731] Rt retention time [0732] TEA triethylamine [0733]
THF tetrahydrofuran
[0734] The compounds were either characterized via proton-NMR in
d.sub.6-dimethylsulfoxid or dchloroform, if not stated otherwise,
on a 400 MHz or 500 MHz NMR instrument (Bruker AVANCE), or by mass
spectrometry, generally recorded via HPLC-MS in a fast gradient on
C18-material (electrospray-ionisation (ESI) mode.
[0735] The magnetic nuclear resonance spectral properties (NMR)
refer to the chemical shifts (.delta.) expressed in parts per
million (ppm). The relative area of the shifts in the .sup.1H NMR
spectrum corresponds to the number of hydrogen atoms for a
particular functional type in the molecule. The nature of the
shift, as regards multiplicity, is indicated as singlet (s), broad
singlet (s. br.), doublet (d), broad doublet (d br.), triplet (t),
broad triplet (t br.), quartet (q), quintet (quint.) and multiplet
(m).
[0736] LC/MS (Halo Purity QC method): The gradient was 5-60% B in
1.5 min then 60-95% B to 2.5 min with a hold at 95% B for 1.2 min
(1.3 mL/min flow rate). Mobile phase A was 10 mM ammonium acetate,
mobile phase B was HPLC grade acetonitrile. The column used for the
chromatography is a 4.6.times.50 mm MAC-MOD Halo C8 column (2.7
.mu.m particles). Detection methods are diode array (DAD) and
evaporative light scattering (ELSD) detection as well as
positive/negative electrospray ionization.
Preparation Examples
Example 1
N-[(1S)-2-Hydroxy-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0737] 4-Pyridin-4-ylbenzoic acid (5.86 g, 29.4 mmol) was dissolved
in 300 ml of THF. Subsequently, N-methylmorpholine (4.04 g, 29.5
mmol), (2S)-2-amino-2-phenylethanol (3.96 g, 29.3 mmol) and
1-hydroxybenzotriazol (3.96 g, 29.3 mmol) were added. Finally EDC
(5.63 g, 29.4 mmol) was added over a period of 5 min and the
heterogenic reaction mixture was stirred for 24 h, whereupon an
oily precipitation occurred. After evaporation of the solvent under
reduced pressure the residue was dissolved in DCM (500 ml), washed
twice with aqueous NaOH (50 ml of a 2 M solution) and subsequently
with water. After drying the organic phase over sodium sulfate and
evaporating the solvent under reduced pressure the raw title
compound was obtained as an oily residue (8.4 g). Column
chromatography (silica gel; eluent: EtOAc with an increasing amount
of MeOH (0 up to 5%)) yielded the pure title compound (5.2 g,
yield: 56%) as a white crystalline product.
[0738] .sup.1H NMR (400 MHz, DMSO-d.sub.6): 8.83 (d, 1H), 8.67 (d,
2H), 8.06 (d, 2H), 7.93 (d, 2H), 7.77 (d, 2H), 7.41 (d, 2H), 7.32
(dd, 2H), 7.23 (dd, 1H), 5.14-5.07 (m, 1H), 4.98 (t, 1H), 3.79-3.63
(m, 2H).
[0739] Formula: C.sub.20H.sub.18N.sub.2O.sub.2
[0740] Calc MW: 318.37
[0741] MS: m/z: 319.1 (M+H).
Example 2
N-[(1R)-3-hydroxy-1-phenylpropyl]-4-pyridin-4-ylbenzamide
[0742] The title compound was prepared according to the procedure
outlined in Example 1, however substituting,
(2S)-2-amino-2-phenylethanol with
(3R)-3-amino-3-phenylpropan-1-ol.
[0743] .sup.1H NMR (400 MHz, DMSO-d.sub.6): 8.88 (d, 1H), 8.66 (d,
2H), 8.01 (d, 2H), 7.91 (d, 2H), 7.75 (d, 2h), 7.39 (d 2H), 7.32
(dd, 2H), 7.21 (dd, 1H), 5.18 (dd, 1H), 4.59 (t, 1H), 3.51-3.39 (m,
2H), 2.12-2.02 (m, 1H), 1.97-1.88 (m, 1H).
[0744] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[0745] Calc MW: 332.41
[0746] MS: m/z: 333.1 (M+H).
Example 3
tert-Butyl-{2-phenyl-2-[(4-pyridin-4-ylbenzoyl)amino]ethyl}carbamate
[0747] The title compound was prepared according to the procedure
outlined in Example 1, however substituting,
(2S)-2-amino-2-phenylethanol with tert-butyl
(2-amino-2-phenylethyl)carbamate.
[0748] Formula: C.sub.25H.sub.27N.sub.3O.sub.3
[0749] Calc MW: 417.51
[0750] MS: m/z: 418.1 (M+H).
Example 4
N-(2-amino-1-phenylethyl)-4-pyridin-4-ylbenzamide x HCl
[0751] The title compound was prepared by BOC cleavage of the
compound obtained in Example 3 with HCl in 2-propanol/DCM at room
temperature.
[0752] Formula: C.sub.20H.sub.19N.sub.3O
[0753] Calc MW: 317.39
[0754] MS: m/z: 318.1 (M+H).
Examples 5 and 6
N-[(1S)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide
N-[(1R)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0755] The title compounds were prepared by subjecting the compound
of Example 4 to a column chromatography with a chiral stationary
phase (Prep HPLC; column: Whelk O 2.5 cm ID.times.25 cm; mobile
phase: hexane/EtOH/MeOH/DEA=5025250.1; flow rate: 40 ml/min;
detector: UV 270 nm; column temp: RT; sample preparation: 10 mg/ml;
load: 10 ml (100 mg))
[0756] .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.48 (d, 1H), 8.66 (d,
2H), 8.58-8.23 (broad signal, 2H), 8.21 (d, 2H), 7.91 (d 2H), 7.77
(d 2H), 7.47 (d, 2H), 7.36 (dd, 2H), 7.27 (dd, 1H), 5.43-5.36 (m,
1H), 3.47 (dd, 1H), 3.14 (dd, 1H).
[0757] Formula: C.sub.20H.sub.19N.sub.3O
[0758] Calc MW: 317.39
[0759] MS: m/z 318.1 (M+H).
[0760] .sup.1H NMR (400 MHz, DMSO-d.sub.6): 9.61 (d, 1H), 8.89 (d,
2H), 8.59-8.46 (broad signal, 2H), 8.25 (d, 4H), 8.07 (d, 2H), 7.48
(d 2H), 7.36 (dd, 2H), 7.28 (dd, 1H), 5.43-5.36 (m, 1H), 3.47 (dd,
1H), 3.14 (dd, 1H).
[0761] Formula: C.sub.20H.sub.19N.sub.3O.
[0762] Calc MW: 317.39
[0763] MS: m/z 318.1 (M+H).
Example 7
N-[(1S)-1-benzyl-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0764] In a microwave vial containing 3 eq. of PS-DCC,
4-(pyridin-4-yl)benzoic acid (20 mg, 0.1 mmol) was added dissolved
in DMA (1.0 ml). Then a solution of HOBT (14 mg, 0.1 mmol)
dissolved in DMA (0.3 ml) was added followed by the addition of
DIEA (36 .mu.l, 0.2 mmol) dissolved in DMA (0.3 ml) and the
addition of (S)-2-amino-3-phenylpropan-1-ol (17 mg, 0.11 mmol)
dissolved in DMA (0.6 ml). The mixture was heated in the microwave
to 100.degree. C. for 600 seconds. The reaction was filtered
through Si-Carbonate, 6 ml-1 g supplied by Silicycle chemical
Division and transferred to 20 ml vials. The reaction was checked
by LC/MS and concentrated to dryness. The residues were dissolved
in 1:1 DMSO/MeOH and purified by reverse phase HPLC (TFA method).
Product was characterized by .sup.1H NMR, MS and LC/MS.
[0765] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O)
.delta.=2.71-2.86 (m, 1H) 2.94-3.02 (m, 1H) 3.42-3.59 (m, 2H)
4.15-4.27 (m, 1H) 7.14-7.22 (m, 1H) 7.23-7.33 (m, 4H) 7.73-7.82 (m,
2H) 7.84-7.97 (m, 4H) 8.61-8.68 (m, 2H);
[0766] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[0767] Calc MW: 332.40
[0768] MS (ESI) positive ion 333 (M+H); negative ion 331 (M-H).
[0769] The following compounds were prepared in an analogous
method:
Example 8
N-[(1S)-1-benzyl-2-hydroxyethyl]-2-fluoro-4-pyridin-4-ylbenzamide
[0770] Formula: C.sub.21H.sub.19F N.sub.2O.sub.2
[0771] Calc MW: 350.39
[0772] ESI-MS: 351 [M+H].sup.+
Example 9
N-[(1S,2S)-2-hydroxy-1-(hydroxymethyl)-2-phenylethyl]-4-pyridin-4-ylbenzam-
ide
[0773] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.38-3.47 (m, 1H) 3.59-3.67 (m, 1H) 4.19-4.27 (m, 1H) 4.95 (d, 1H)
7.17-7.25 (m, 1H) 7.31 (t, 2H) 7.34-7.41 (m, 2H) 7.73-7.81 (m, 2H)
7.81-7.98 (m, 4H) 8.58-8.72 (m, 2H);
[0774] Formula: C.sub.21H.sub.20N.sub.2O.sub.3
[0775] Calc MW: 348.40
[0776] MS (ESI) negative ion 347 (M-H).
Example 10
N-[1-(4-chlorobenzyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0777] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.73-2.85 (m, 1H) 2.97 (dd, 1H) 3.43-3.60 (m, 2H) 4.09-4.29 (m, 1H)
7.24-7.36 (m, 4H) 7.71-7.83 (m, 2H) 7.85-7.98 (m, 4H) 8.59-8.73 (m,
2H);
[0778] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[0779] Calc MW: 366.85
[0780] MS (ESI) negative ion 365 (M-H).
Example 11
N-[(1R)-2-hydroxy-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0781] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.54-3.72 (m, 2H) 5.00-5.21 (m, 1H) 7.24-7.29 (m, 1H) 7.32-7.37 (m,
2H) 7.38-7.45 (m, 2H) 7.76-7.81 (m, 2H) 7.89-7.99 (m, 2H) 8.00-8.09
(m, 2H) 8.60-8.75 (m, 2H);
[0782] Formula: C.sub.20H.sub.18N.sub.2O.sub.2
[0783] Calc MW: 318.37
[0784] MS (ESI) positive ion 319 (M+H); negative ion 317 (M-H).
Example 12
N-(1-methyl-3-phenylpropyl)-4-pyridin-4-ylbenzamide
[0785] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.20 (d, 3H) 1.72-1.98 (m, 2H) 2.58-2.70 (m, 2H) 3.97-4.12 (m, 1H)
7.13-7.24 (m, 3H) 7.25-7.35 (m, 2H) 7.74-7.82 (m, 2H) 7.89-7.93 (m,
2H) 7.96-8.03 (m, 2H) 8.56-8.75 (m, 2H);
[0786] Formula: C.sub.22H.sub.22N.sub.2O
[0787] Calc MW: 330.43
[0788] MS (ESI) positive ion 331 (M+H); negative ion 329 (M-H).
Example 13
N-[(1S,2S)-2-hydroxy-1-(methoxymethyl)-2-phenylethyl]-4-pyridin-4-ylbenzam-
ide
[0789] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.24-3.29 (m, 3H) 3.31-3.39 (m, 1H) 3.50-3.60 (m, 1H) 4.34-4.41 (m,
1H) 4.89 (d, 1H) 7.15-7.28 (m, 1H) 7.26-7.42 (m, 4H) 7.72-7.79 (m,
2H) 7.84-7.98 (m, 4H) 8.63-8.69 (m, 2H);
[0790] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[0791] Calc MW: 362.43
[0792] MS (ESI) positive ion 363 (M+H); negative ion 361 (M-H).
Example 14
N-[(1S)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethyl]-4-pyridin-4-ylbenzamide
[0793] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.90-2.99 (m, 1H) 3.02-3.10 (m, 1H) 3.47-3.63 (m, 2H) 4.25-4.33 (m,
1H) 7.00 (t, 1H) 7.08 (t, 1H) 7.15-7.18 (m, 1H) 7.34 (d, 1H) 7.65
(d, 1H) 7.73-7.82 (m, 2H) 7.85-8.16 (m, 4H) 8.61-8.68 (m, 2H);
Formula: C.sub.23H.sub.21N.sub.3O.sub.2
[0794] Calc MW: 371.44
[0795] MS (ESI) positive ion 372 (M+H); negative ion 370
(M-H).sup.+
Example 15
N-[(1S)-2-hydroxy-1-(4-hydroxybenzyl)ethyl]-4-pyridin-4-ylbenzamide
[0796] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.63-2.70 (m, 1H) 2.80-2.88 (m, 1H) 3.36-3.59 (m, 2H) 3.99-4.24 (m,
1H) 6.56-6.72 (m, 2H) 6.98-7.13 (m, 2H) 7.71-7.80 (m, 2H) 7.84-7.96
(m, 4H) 8.51-8.82 (m, 2H);
[0797] Formula: C.sub.21H.sub.22N.sub.2O.sub.3
[0798] Calc MW: 348.40
[0799] MS (ESI) negative ion 347 (M-H).
Example 16
N-(1-benzyl-2-methoxyethyl)-4-pyridin-4-ylbenzamide
[0800] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.70-2.97 (m, 2H) 3.25-3.32 (m, 3H) 3.37-3.59 (m, 2H) 4.21-4.46 (m,
1H) 7.10-7.22 (m, 1H) 7.23-7.34 (m, 4H) 7.70-7.83 (m, 2H) 7.85-8.02
(m, 4H) 8.54-8.71 (m, 2H);
[0801] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[0802] Calc MW: 346.43
[0803] MS (ESI) positive ion 347 (M+H); negative ion 345 (M-H)
Example 17
N-[(1R)-1-benzyl-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0804] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.73-2.83 (m, 1H) 2.91-3.05 (m, 1H) 3.37-3.58 (m, 2H) 4.11-4.27 (m,
1H) 7.08-7.22 (m, 1H) 7.22-7.34 (m, 4H) 7.67-7.83 (m, 2H) 7.84-8.02
(m, 4H) 8.52-8.73 (m, 2H);
[0805] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[0806] Calc MW: 332.40
[0807] MS (ESI) positive ion 333 (M+H); negative ion 331 (M-H).
Example 18
N-[(1R)-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0808] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.00-5.26 (m, 1H) 7.16-7.27 (m, 1H) 7.29-7.44 (m, 4H)
7.68-7.83 (m, 2H) 7.86-7.94 (m, 2H) 7.98-8.10 (m, 2 H) 8.50-8.78
(m, 2H);
[0809] Formula: C.sub.20H.sub.18N.sub.2O
[0810] Calc MW: 302.38
[0811] MS (ESI) positive ion 303 (M+H); negative ion 301 (M-H).
Example 19
N-[(1S)-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0812] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.05-5.26 (m, 1H) 7.18-7.30 (m, 1H) 7.31-7.46 (m, 4H)
7.70-7.80 (m, 2H) 7.88-7.95 (m, 2H) 7.98-8.05 (m, 2H) 8.63-8.68 (m,
2H);
[0813] Formula: C.sub.20H.sub.18N.sub.2O
[0814] Calc MW: 302.38
[0815] MS (ESI) positive ion 303 (M+H); negative ion 301 (M-H).
Example 20
N-{(1S,2S)-2-hydroxy-1-(hydroxymethyl)-2-[4-(methylthio)phenyl]ethyl}-4-py-
ridin-4-ylbenzamide
[0816] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.41-2.45 (m, 3H) 3.37-3.45 (m, 1H) 3.58-3.66 (m, 1H) 4.14-4.25 (m,
1H) 4.86-4.94 (m, 1H) 7.13-7.23 (m, 2H) 7.25-7.35 (m, 2H) 7.74-7.83
(m, 2H) 7.86-7.94 (m, 4H) 8.61-8.72 (m, 2H);
[0817] Formula: C.sub.22H.sub.22N.sub.2O.sub.3S
[0818] Calc MW: 394.49
[0819] MS (ESI) positive ion 395 (M+H); negative ion 393 (M-H)
Example 21
N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-4-pyridin-4-ylbenzamide
[0820] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.89-2.95 (m, 1H) 3.10-3.18 (m, 1H) 4.52-4.59 (m, 1H) 5.47 (d, 1H)
7.15-7.32 (m, 4H) 7.73-7.86 (m, 2H) 7.90-7.96 (m, 2H) 8.02-8.14 (m,
2H) 8.53-8.78 (m, 2H);
[0821] Formula: C.sub.21H.sub.18N.sub.2O.sub.2
[0822] Calc MW: 330.39
[0823] MS (ESI) positive ion 331 (M+H); negative ion 329 (M-H).
Example 22
N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-4-pyridin-4-ylbenzamide
[0824] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.85-2.97 (m, 1H) 3.07-3.20 (m, 1H) 4.53-4.59 (m, 1H) 5.47 (d, 1H)
7.20-7.35 (m, 4H) 7.74-7.87 (m, 2H) 7.88-7.96 (m, 2H) 8.02-8.11 (m,
2H) 8.61-8.70 (m, 2H));
[0825] Formula: C.sub.21H.sub.18N.sub.2O.sub.2
[0826] Calc MW: 330.39
[0827] MS (ESI) positive ion 331 (M+H); negative ion 329 (M-H).
Example 23
N-[(1R)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethyl]-4-pyridin-4-ylbenzamide
[0828] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.86-3.10 (m, 2H) 3.46-3.63 (m, 2H) 4.19-4.32 (m, 1H) 6.95-7.02 (m,
1H) 7.05-7.10 (m, 1H) 7.13-7.18 (m, 1H) 7.33 (d, 1H) 7.64 (d, 1H)
7.74-7.82 (m, 2H) 7.85-7.98 (m, 4H) 8.61-8.71 (m, 2H);
[0829] Formula: C.sub.23H.sub.21N.sub.3O.sub.2
[0830] Calc MW: 371.44
[0831] MS (ESI) positive ion 372 (M+H); negative ion 370 (M-H).
Example 24
N-[(1R)-2-hydroxy-1-(4-hydroxybenzyl)ethyl]-4-pyridin-4-ylbenzamide
[0832] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.61-2.73 (m, 1H) 2.78-2.93 (m, 1H) 3.37-3.54 (m, 2H) 3.98-4.18 (m,
1H) 6.57-6.72 (m, 2H) 6.93-7.23 (m, 2H) 7.69-7.81 (m, 2H) 7.83-8.01
(m, 4H) 8.56-8.76 (m, 2H);
[0833] Formula: C.sub.21H.sub.20N.sub.2O.sub.3
[0834] Calc MW: 348.40
[0835] MS (ESI) negative ion 347 (M-H).
Example 25
N-((1R,2R)-2-{[(4-methylphenyl)sulfonyl]amino}-1,2-diphenylethyl)-4-pyridi-
n-4-ylbenzamide
[0836] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.17-2.26 (m, 3H) 4.81-4.92 (m, 1H) 5.35-5.45 (m, 1H) 6.96-7.32 (m,
14H) 7.77-7.83 (m, 2H) 7.88-7.95 (m, 4H) 8.60-8.72 (m, 2H) 8.83 (d,
1H);
[0837] Formula: C.sub.33H.sub.29N.sub.3O.sub.3S
[0838] Calc MW: 547.68
[0839] MS (ESI) negative ion 546 (M-H).
Example 26
N-{(1S)-1-[4-(benzyloxy)benzyl]-2-hydroxyethyl}-4-pyridin-4-ylbenzamide
[0840] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.67-2.77 (m, 1H) 2.86-2.96 (m, 1H) 3.39-3.53 (m, 2H) 4.09-4.24 (m,
1H) 4.97-5.06 (m, 2H) 6.86-6.93 (m, 2H) 7.14-7.23 (m, 2H) 7.25-7.49
(m, 5H) 7.73-7.79 (m, 2H) 7.85-7.96 (m, 4H) 8.53-8.74 (m, 2H);
[0841] Formula: C.sub.28H.sub.26N.sub.2O.sub.3
[0842] Calc MW: 438.52
[0843] MS (ESI) negative ion 437 (M-H).
Example 27
N-[1-(3,5-dichlorophenyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0844] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.62-3.71 (m, 2H) 4.96-5.13 (m, 1H) 7.42-7.52 (m, 3H) 7.73-7.84 (m,
2H) 7.89-8.07 (m, 4H) 8.61-8.72 (m, 2H);
[0845] Formula: C.sub.20H.sub.16Cl.sub.2N.sub.2O.sub.2
[0846] Calc MW: 387.26
[0847] MS (ESI) negative ion 385 (M-H).
Example 28
N-[(1S)-1-benzyl-2-pyrrolidin-1-ylethyl]-4-pyridin-4-ylbenzamide
[0848] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.47-2.17 (m, 4H) 2.67-3.54 (m, 8H) 4.28-4.75 (m, 1H) 7.15-7.21 (m,
1H) 7.23-7.29 (m, 4H) 7.74-7.80 (m, 2H) 7.84-7.96 (m, 4H) 8.46-8.79
(m, 2H);
[0849] Formula: C.sub.25H.sub.27N.sub.3O
[0850] Calc MW: 385.51
[0851] MS (ESI) positive ion 386 (M+H); negative ion 384 (M-H).
Example 29
N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]-4-pyridin-4-ylbenzamide
[0852] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
4.94 (d, 1H) 5.18 (d, 1H) 7.19-7.37 (m, 6H) 7.44-7.51 (m, 4H)
7.68-7.86 (m, 6H) 8.60-8.69 (m, 2H);
[0853] Formula: C.sub.26H.sub.22N.sub.2O.sub.2
[0854] Calc MW: 394.47
[0855] MS (ESI) positive ion 395 (M+H); negative ion 393 (M-H).
Example 30
N-[2-(dimethylamino)-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0856] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.21-2.26 (m, 6H) 2.39-2.47 (m, 1H) 2.79-2.88 (m, 1H) 5.17-5.25 (m,
1H) 7.22-7.49 (m, 5H) 7.75-7.82 (m, 2H) 7.89-7.95 (m, 2H) 8.01-8.08
(m, 2H) 8.62-8.71 (m, 2H);
[0857] Formula: C.sub.22H.sub.23N.sub.3O
[0858] Calc MW: 345.44
[0859] MS (ESI) positive ion 346 (M+H); negative ion 344 (M-H).
Example 31
N-(1-phenyl-2-pyrrolidin-1-ylethyl)-4-pyridin-4-ylbenzamide
[0860] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.57-1.81 (m, 4H) 2.53-2.58 (m, 4H) 2.61-2.69 (m, 1H) 2.92-3.14 (m,
1H) 5.10-5.26 (m, 1H) 7.21-7.29 (m, 1H) 7.32-7.38 (m, 2H) 7.40-7.48
(m, 2H) 7.72-7.83 (m, 2H) 7.87-7.98 (m, 2H) 7.99-8.10 (m, 2H)
8.54-8.71 (m, 2H);
[0861] Formula: C.sub.24H.sub.25N.sub.3O
[0862] Calc MW: 371.48
[0863] MS (ESI) positive ion 372 (M+H); negative ion 370 (M-H).
Example 32
N-(2-morpholin-4-yl-1-phenylethyl)-4-pyridin-4-ylbenzamide
[0864] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.32-2.52 (m, 5H) 2.81-2.93 (m, 1H) 3.47-3.63 (m, 4H) 5.09-5.42 (m,
1H) 7.20-7.31 (m, 1H) 7.33-7.40 (m, 2H) 7.39-7.50 (m, 2H) 7.74-7.81
(m, 2H) 7.88-8.00 (m, 2H) 7.96-8.09 (m, 2H) 8.56-8.75 (m, 2H);
[0865] Formula: C.sub.24H.sub.25N.sub.3O.sub.2
[0866] Calc MW: 387.48MS (ESI) positive ion 388 (M+H); negative ion
386 (M-H).
Example 33
N-[2-(4-methylpiperazin-1-yl)-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0867] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.04-2.16 (m, 3H) 2.20-2.41 (m, 4H) 2.40-2.53 (m, 5H) 2.82-2.91 (m,
1H) 5.10-5.43 (m, 1H) 7.19-7.30 (m, 1H) 7.32-7.38 (m, 2H) 7.39-7.46
(m, 2H) 7.75-7.84 (m, 2H) 7.89-7.97 (m, 2H) 7.99-8.09 (m, 2H)
8.54-8.74 (m, 2H);
[0868] Formula: C.sub.25H.sub.28N.sub.4O
[0869] Calc MW: 400.52
[0870] MS (ESI) positive ion 401 M+H); negative ion 399M-H).
Example 34
N-[(2S)-2-hydroxy-1,2-diphenylethyl]-4-pyridin-4-ylbenzamide
[0871] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
4.94 (d, 1H) 5.17 (d, 1H) 7.11-7.38 (m, 6H) 7.43-7.56 (m, 4H)
7.68-7.90 (m, 6H) 8.55-8.67 (m, 2H);
[0872] Formula: C.sub.26H.sub.22N.sub.2O.sub.2
[0873] Calc MW: 394.47
[0874] MS (ESI) positive ion 395 (M+H); negative ion 393 (M-H).
Example 35
N-[2-(1H-imidazol-1-yl)-1-phenylethyl]-4-pyridin-4-ylbenzamide
[0875] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
4.41 (d, 2H) 5.44 (t, 1H) 6.83-6.90 (m, 1 H) 7.27-7.36 (m, 2H)
7.38-7.44 (m, 2H) 7.50-7.58 (m, 2H) 7.69-7.74 (m, 1H) 7.75-7.81 (m,
2H) 7.84-7.99 (m, 4H) 8.52-8.70 (m, 2H);
[0876] Formula: C.sub.23H.sub.20N.sub.4O
[0877] Calc MW: 368.44
[0878] MS (ESI) positive ion 369 (M+H); negative ion 367 (M-H).
Example 36
N-(1-phenyl-2-piperidin-1-ylethyl)-4-pyridin-4-ylbenzamide
[0879] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.28-1.52 (m, 6H) 2.29-2.52 (m, 4H) 2.81-2.90 (m, 1H) 2.99-3.09 (m,
1H) 5.18-5.33 (m, 1H) 7.21-7.29 (m, 1H) 7.31-7.38 (m, 2H) 7.39-7.44
(m, 2H) 7.74-7.82 (m, 2H) 7.90-7.96 (m, 2H) 7.99-8.06 (m, 2H)
8.61-8.70 (m, 2H);
[0880] Formula: C.sub.25H.sub.27N.sub.3O
[0881] Calc MW: 385.51
[0882] MS (ESI) positive ion 386 (M+H); negative ion 384 (M-H).
Example 37
N-[1-(4-ethoxyphenyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0883] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.29 (t, 3H) 3.61-3.67 (m, 1H) 3.69-3.73 (m, 1H) 3.99 (q, 2H)
4.93-5.11 (m, 1H) 6.85-6.90 (m, 2H) 7.25-7.36 (m, 2H) 7.67-7.81 (m,
2H) 7.88-7.97 (m, 2H) 8.00-8.06 (m, 2H) 8.53-8.74 (m, 2H);
[0884] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[0885] Calc MW: 362.43
[0886] MS (ESI) positive ion 363 (M+H); negative ion 361 (M-H).
Example 38
N-[(1R)-1-(4-tert-butylphenyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0887] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.20-1.34 (m, 9H) 3.60-3.74 (m, 2H) 4.94-5.18 (m, 1H) 7.29-7.35 (m,
4H) 7.73-7.83 (m, 2H) 7.89-7.94 (m, 2H) 8.00-8.09 (m, 2H) 8.60-8.68
(m, 2H);
[0888] Formula: C.sub.24H.sub.26N.sub.2O.sub.2
[0889] Calc MW: 374.48
[0890] MS (ESI) positive ion 375 (M+H); negative ion 373 (M-H).
Example 39
N-(2-hydroxy-1-pyridin-3-ylethyl)-4-pyridin-4-ylbenzamide
[0891] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.76-3.86 (m, 2H) 5.13 (t, 1H) 7.36-7.47 (m, 1H) 7.75-7.81 (m, 2H)
7.84-7.89 (m, 1H) 7.91-7.97 (m, 2H) 8.03-8.08 (m, 2 H) 8.41-8.50
(m, 1H) 8.57-8.64 (m, 1H) 8.65-8.71 (m, 2H);
[0892] Formula: C.sub.19H.sub.17N.sub.3O.sub.2
[0893] Calc MW: 319.36
[0894] MS (ESI) positive ion 320 (M+H); negative ion 318 (M-H).
Example 40
N-[1-(2,4-dimethylphenyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0895] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.17-2.27 (m, 3H) 2.37-2.44 (m, 3H) 3.47-3.72 (m, 2H) 5.20-5.36 (m,
1H) 6.93-7.04 (m, 2H) 7.25-7.34 (m, 1H) 7.73-7.82 (m, 2H) 7.89-7.95
(m, 2H) 7.99-8.06 (m, 2H) 8.60-8.72 (m, 2H);
[0896] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[0897] Calc MW: 346.43
[0898] MS (ESI) positive ion 347 (M+H); negative ion 345 (M-H).
Example 41
N-[1-(3,4-dimethylphenyl)-2-hydroxyethyl]-4-pyridin-4-ylbenzamide
[0899] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.25-2.29 (m, 3H) 2.29-2.33 (m, 3H) 3.50-3.69 (m, 2H) 5.26-5.45 (m,
1H) 7.03-7.05 (m, 2H) 7.23-7.30 (m, 1H) 7.73-7.86 (m, 2H) 7.88-7.97
(m, 2H) 7.97-8.10 (m, 2H) 8.54-8.70 (m, 2H);
[0900] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[0901] Calc MW: 346.43
[0902] MS (ESI) positive ion 347 (M+H); negative ion 345 (M-H).
Example 42
N-[2-hydroxy-1-(4-isopropylphenyl)ethyl]-4-pyridin-4-ylbenzamide
[0903] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.18 (d, 6H) 2.80-2.91 (m, 1H) 3.59-3.71 (m, 2H) 5.00-5.10 (m, 1H)
7.16-7.23 (m, 2H) 7.26-7.35 (m, 2H) 7.74-7.81 (m, 2H) 7.86-7.95 (m,
2H) 7.94-8.10 (m, 2H) 8.54-8.72 (m, 2H); MS (ESI) positive ion 361
(M+H); negative ion 359 (M-H).
[0904] Formula: C.sub.23H.sub.24N.sub.2O.sub.2
[0905] Calc MW: 360.45
[0906] MS (ESI) positive ion 361 (M+H); negative ion 359 (M-H).
Example 43
N-{2-hydroxy-1-[4-(methylthio)phenyl]ethyl}-4-pyridin-4-ylbenzamide
[0907] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.41-2.48 (m, 3H) 3.57-3.71 (m, 2H) 4.97-5.16 (m, 1H) 7.20-7.26 (m,
2H) 7.33-7.40 (m, 2H) 7.73-7.81 (m, 2H) 7.87-7.99 (m, 2H) 7.99-8.10
(m, 2H) 8.56-8.74 (m, 2H);
[0908] Formula: C.sub.21H.sub.20N.sub.2O.sub.2S
[0909] Calc MW: 364.47
[0910] MS (ESI) positive ion 365 (M+H); negative ion 363 (M-H).
Example 44
N-[2-amino-1-(4-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide
[0911] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.14-3.25 (m, 1H) 3.28-3.37 (m, 1H) 3.73-3.76 (m, 3H) 5.27-5.38 (m,
1H) 6.97 (d, 2H) 7.38 (d, 2H) 8.07-8.14 (m, 4H) 8.32 (d, 2H) 8.90
(d, 2H);
[0912] Formula: C.sub.21H.sub.21N.sub.3O.sub.2
[0913] Calc MW: 347.42
[0914] MS (ESI) positive ion 348 (M+H)
Example 45
N-[2-amino-1-(3-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide
[0915] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.17-3.29 (m, 1H) 3.30-3.43 (m, 1H) 3.73-3.79 (m, 3H) 5.31-5.41 (m,
1H) 6.86-6.94 (m, 1H) 7.00-7.08 (m, 2H) 7.27-7.38 (m, 1H) 8.05-8.18
(m, 4H) 8.30 (d, 2H) 8.89 (d, 2H);
[0916] Formula: C.sub.21H.sub.21N.sub.3O.sub.2
[0917] Calc MW: 347.42
[0918] MS (ESI) positive ion 348 (M+H).
Example 46
N-[2-amino-1-(4-methylphenyl)ethyl]-4-pyridin-4-ylbenzamide
[0919] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
2.24-2.35 (m, 3H) 3.15-3.24 (m, 1H) 3.29-3.41 (m, 1H) 5.30-5.38 (m,
1H) 7.19 (d, 2H) 7.36 (d, 2H) 8.07-8.16 (m, 4H) 8.33 (d, 2H) 8.91
(d, 2H);
[0920] Formula: C.sub.21H.sub.21N.sub.3O
[0921] Calc MW: 331.42
[0922] MS (ESI) positive ion 332 (M+H).
Example 47
N-[(1R)-1-(1-naphthyl)ethyl]-4-pyridin-4-ylbenzamide
[0923] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.65 (d, 3H) 5.91-6.05 (m, 1H) 7.48-7.69 (m, 4H) 7.86 (d, 1H) 7.97
(d, 1H) 8.04-8.15 (m, 4H) 8.22 (d, 1H) 8.27-8.33 (m, 2H) 8.81-8.95
(m, 2H);
[0924] Formula: C.sub.24H.sub.20N.sub.2O
[0925] Calc MW: 352.44
[0926] MS (ESI) positive ion 353 (M+H); negative ion 351 (M-H).
Example 48
N-(1,2-diphenylethyl)-4-pyridin-4-ylbenzamide
[0927] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
3.01-3.28 (m, 2H) 5.16-5.42 (m, 1H) 7.14-7.54 (m, 10H) 7.90-8.07
(m, 4H) 8.15-8.29 (m, 2H) 8.74-8.96 (m, 2H);
[0928] Formula: C.sub.26H.sub.22N.sub.2O
[0929] Calc MW: 378.48
[0930] MS (ESI) positive ion 379 (M+H); negative ion 377 (M-H).
Example 49
N-[(4-chlorophenyl)(phenyl)methyl]-4-pyridin-4-ylbenzamide
[0931] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
6.39-6.45 (m, 1H) 7.27-7.35 (m, 1H) 7.35-7.53 (m, 8H) 8.01-8.15 (m,
4H) 8.15-8.23 (m, 2H) 8.78-8.88 (m, 2H);
[0932] Formula: C.sub.25H.sub.19ClN.sub.2O
[0933] Calc MW: 398.90
[0934] MS (ESI) positive ion 399 (M+H); negative ion 397 (M-H).
Example 50
N-(1-methyl-3-phenylpropyl)-4-pyridin-4-ylbenzamide
[0935] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.20 (d, 3H) 1.69-1.96 (m, 2H) 2.58-2.67 (m, 2H) 3.97-4.14 (m, 1H)
7.14-7.33 (m, 5H) 8.01-8.09 (m, 4H) 8.19-8.33 (m, 2H) 8.81-8.91 (m,
2H);
[0936] Formula: C.sub.22H.sub.22N.sub.2O
[0937] Calc MW: 330.43
[0938] MS (ESI) positive ion 331 (M+H); negative ion 329 (M-H).
Example 51
N-[(1S)-1-(1-naphthyl)ethyl]-4-pyridin-4-ylbenzamide
[0939] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.66 (d, 3H) 5.95-6.03 (m, 1H) 7.49-7.70 (m, 4H) 7.85 (d, 1H) 7.97
(d, 1H) 8.05-8.14 (m, 4H) 8.20-8.25 (m, 1H) 8.29-8.36 (m, 2H)
8.80-8.96 (m, 2H);
[0940] Formula: C.sub.24H.sub.20N.sub.2O
[0941] Calc MW: 352.44
[0942] MS (ESI) positive ion 353 (M+H); negative ion 351 (M-H).
Example 52
N-[1-(5-chloro-1-benzofuran-2-yl)ethyl]-4-pyridin-4-ylbenzamide
[0943] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.65 (d, 3H) 5.45 (q, 1H) 6.77-6.87 (m, 1H) 7.30 (d, 1H) 7.57 (d,
1H) 7.65-7.74 (m, 1H) 8.07-8.16 (m, 4H) 8.35 (d, 2H) 8.91 (d,
2H);
[0944] Formula: C.sub.22H.sub.17ClN.sub.2O.sub.2
[0945] Calc MW: 376.85
[0946] MS (ESI) positive ion 377 (M+H).
Example 53
N-[1-(2-fury))ethyl]-4-pyridin-4-ylbenzamide
[0947] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.52 (d, 3H) 5.30 (q, 1H) 6.28-6.35 (m, 1H) 6.39-6.48 (m, 1H)
7.53-7.60 (m, 1H) 8.05-8.13 (m, 4H) 8.34 (d, 2H) 8.90 (d, 2H);
[0948] Formula: C.sub.18H.sub.16N.sub.2O.sub.2
[0949] Calc MW: 292.34
[0950] MS (ESI) positive ion 293 (M+H).
Example 54
N-[1-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-4-pyridin-4-ylbenzamide
[0951] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.48 (d, 3H) 2.19-2.29 (m, 3H) 3.65-3.74 (m, 3H) 5.12 (q, 1H)
7.40-7.49 (m, 1H) 7.99-8.14 (m, 4H) 8.42 (d, 2H) 8.94 (d, 2H);
[0952] Formula: C.sub.19H.sub.20N.sub.4O
[0953] Calc MW: 320.4
[0954] MS (ESI) positive ion 321 (M+H).
Example 55
N-{1-[1-(2-fluorophenyl)-1H-pyrazol-4-yl]ethyl}-4-pyridin-4-ylbenzamide
[0955] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.46-1.64 (m, 3H) 5.30 (q, 1H) 7.26-7.58 (m, 3H) 7.67-7.91 (m, 2H)
7.96-8.20 (m, 5H) 8.25-8.43 (m, 2H) 8.77-9.03 (m, 2 H);
[0956] Formula: C.sub.23H.sub.19FN.sub.4O
[0957] Calc MW: 386.43
[0958] MS (ESI) positive ion 387 (M+H).
Example 56
N-{1-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]ethyl}-4-pyridin-4-ylbenzamide
[0959] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.57 (d, 3H) 5.27 (q, 1H) 7.27-7.43 (m, 2H) 7.72-7.77 (m, 1H)
7.81-7.87 (m, 2H) 8.07-8.14 (m, 4H) 8.34-8.42 (m, 3H) 8.92 (d,
2H);
[0960] Formula: C.sub.23H.sub.19F N.sub.4O
[0961] Calc MW: 386.43
[0962] MS (ESI) positive ion 387 (M+H).
Example 57
N-{1-[1-(4-methoxyphenyl)-1H-pyrazol-4-yl]ethyl}-4-pyridin-4-ylbenzamide
[0963] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.57 (d, 3H) 3.78-3.82 (m, 3H) 5.25 (q, 1H) 7.05 (d, 2H) 7.66-7.72
(m, 3H) 8.05-8.12 (m, 4H) 8.26-8.30 (m, 1H) 8.36 (d, 2H) 8.91 (d,
2H);
[0964] Formula: C.sub.24H.sub.22N.sub.4O.sub.2
[0965] Calc MW: 398.47
[0966] MS (ESI) positive ion 399 (M+H).
Example 58
N-{1-[1-(2-methoxyphenyl)-1H-pyrazol-4-yl]ethyl}-4-pyridin-4-ylbenzamide
[0967] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.57 (d, 3H) 3.86-3.88 (m, 3H) 5.27 (q, 1 H) 7.05-7.12 (m, 1H) 7.23
(d, 1H) 7.34-7.42 (m, 1H) 7.59 (d, 1H) 7.68-7.74 (m, 1H) 8.08-8.14
(m, 5H) 8.40 (d, 2H) 8.93 (d, 2H);
[0968] Formula: C.sub.24H.sub.22N.sub.4O.sub.2
[0969] Calc MW: 398.47
[0970] MS (ESI) positive ion 399 (M+H).
Example 59
N-[1-(3-propyl-1,2,4-oxadiazol-5-yl)ethyl]-4-pyridin-4-ylbenzamide
[0971] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
0.91 (t, 3H) 1.64 (d, 3H) 1.66-1.72 (m, 2H) 2.67 (t, 2H) 5.39 (q,
1H) 8.08-8.13 (m, 4H) 8.31 (d, 2H) 8.88 (d, 2H);
[0972] Formula: C.sub.19H.sub.2O N.sub.4O.sub.2
[0973] Calc MW: 336.4
[0974] MS (ESI) positive ion 337 (M+H).
Example 60
N-[1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]-4-pyridin-4-ylbenzamide
[0975] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.73 (d, 3H) 5.49 (q, 1H) 7.55-7.64 (m, 3H) 7.99-8.04 (m, 2H)
8.11-8.18 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H);
[0976] Formula: C.sub.22H.sub.18N.sub.4O.sub.2
[0977] Calc MW: 370.41
[0978] MS (ESI) positive ion 371 (M+H).
Example 61
4-pyridin-4-yl-N-[1-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)ethyl]benzamide
[0979] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.75 (d, 3H) 5.52 (q, 1H) 8.08 (d, 2H) 8.11-8.18 (m, 4H) 8.39 (d,
2H) 8.86 (d, 2H) 8.93 (d, 2H);
[0980] Formula: C.sub.21H.sub.17N.sub.5O.sub.2
[0981] Calc MW: 371.4
[0982] MS (ESI) positive ion 372 (M+H).
Example 62
N-[1-(4-propyl-4H-1,2,4-triazol-3-yl)ethyl]-4-pyridin-4-ylbenzamide
[0983] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
0.84 (t, 3H) 1.66 (d, 3H) 1.70-1.82 (m, 2 H) 4.01-4.15 (m, 2H) 5.48
(q, 1H) 8.05-8.11 (m, 4H) 8.30 (d, 2H) 8.88 (d, 2H) 8.94-9.02 (m,
1H);
[0984] Formula: C.sub.19H.sub.21N.sub.5O
[0985] Calc MW: 335.41
[0986] MS (ESI) positive ion 336 (M+H).
Example 63
N-{1-[4-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl]ethyl}-4-pyridin-4-ylbenzam-
ide
[0987] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.68 (d, 3H) 3.21-3.31 (m, 3H) 3.58-3.73 (m, 2H) 4.29-4.44 (m, 2H)
5.48 (q, 1H) 8.04-8.21 (m, 4H) 8.39 (d, 2H) 8.91 (d, 2 H) 8.99-9.05
(m, 1H);
[0988] Formula: C.sub.19H.sub.21N.sub.5O.sub.2
[0989] Calc MW: 351.41
[0990] MS (ESI) positive ion 352 (M+H).
Example 64
N-[1-(4-cyclopentyl-4H-1,2,4-triazol-3-yl)ethyl]-4-pyridin-4-ylbenzamide
[0991] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.56-1.67 (m, 2H) 1.71 (d, 3H) 1.76-1.84 (m, 2H) 1.85-1.96 (m, 2H)
1.99-2.10 (m, 1H) 2.20-2.31 (m, 1H) 4.73-4.88 (m, 1H) 5.56 (q, 1H)
8.06-8.14 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H) 9.38-9.44 (m, 1H);
[0992] Formula: C.sub.21H.sub.23N.sub.5O
[0993] Calc MW: 361.45
[0994] MS (ESI) positive ion 362 (M+H).
Example 65
N-{1-[4-(3-methoxypropyl)-4H-1,2,4-triazol-3-yl]ethyl}-4-pyridin-4-ylbenza-
mide
[0995] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.70 (d, 3H) 1.95-2.12 (m, 2H) 3.14-3.21 (m, 3H) 3.26-3.45 (m, 2H)
4.13-4.31 (m, 2H) 5.51 (q, 1H) 8.05-8.17 (m, 4H) 8.39 (d, 2H) 8.91
(d, 2H) 9.18-9.27 (m, 1H);
[0996] Formula: C.sub.20H.sub.23N.sub.5O.sub.2
[0997] Calc MW: 365.44
[0998] MS (ESI) positive ion 366 (M+H).
Example 66
N-[1-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-4-pyridin-4-ylbenzamide
[0999] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.27 (t, 3H) 1.50 (d, 3H) 2.27 (s, 3H) 2.33 (s, 3H) 4.02 (q, 2H)
5.04 (q, 1H) 8.00-8.14 (m, 4H) 8.39 (d, 2H) 8.92 (d, 2H);
[1000] Formula: C.sub.21H.sub.24N.sub.4O
[1001] Calc MW: 348.45
[1002] MS (ESI) positive ion 349 (M+H).
Example 67
N-{1-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-4-pyridin-4-ylbenzami-
de
[1003] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.73 (d, 3H) 5.49 (q, 1H) 7.66 (d, 2H) 8.03 (d, 2H) 8.09-8.16 (m,
4H) 8.34 (d, 2H) 8.90 (d, 2H);
[1004] Formula: C.sub.22H.sub.17ClN.sub.4O.sub.2
[1005] Calc MW: 404.86
[1006] MS (ESI) positive ion 405 (M+H).
Example 68
N-{1-[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl}-4-pyridin-4-ylbenzami-
de
[1007] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.73 (d, 3H) 2.38 (s, 3H) 5.48 (q, 1H) 7.38 (d, 2H) 7.89 (d, 2H)
8.07-8.16 (m, 4H) 8.32 (d, 2H) 8.89 (d, 2H);
[1008] Formula: C.sub.23H.sub.20N.sub.4O.sub.2
[1009] Calc MW: 384.44
[1010] MS (ESI) positive ion 385 (M+H).
Example 69
N-{1-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]ethyl}-4-pyridin-4-ylbenzami-
de
[1011] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.74 (d, 3H) 2.40 (s, 3H) 5.48 (q, 1H) 7.39-7.51 (m, 2H) 7.76-7.85
(m, 2H) 8.09-8.17 (m, 4H) 8.39 (d, 2H) 8.93 (d, 2H);
[1012] Formula: C.sub.23H.sub.20N.sub.4O.sub.2
[1013] Calc MW: 384.44
[1014] MS (ESI) positive ion 385 (M+H).
Example 70
4-pyridin-4-yl-N-[1-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethyl]benzamide
[1015] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 2.28 (s, 3H) 2.35 (s, 3H) 3.70 (s, 3H) 5.03 (q, 1H)
8.03-8.17 (m, 4H) 8.42 (d, 2H) 8.94 (d, 2H);
[1016] Formula: C.sub.20H.sub.22N.sub.4O
[1017] Calc MW: 334.42
[1018] MS (ESI) positive ion 335 (M+H).
Example 71
N-[1-(5-methyl-2-fury))ethyl]-4-pyridin-4-ylbenzamide
[1019] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.49 (d, 3H) 2.26 (s, 3H) 5.15-5.30 (m, 1H) 5.99 (s, 1H) 6.20 (s,
1H) 7.97-8.18 (m, 4H) 8.38 (d, 2H) 8.90 (d, 2H);
[1020] Formula: C.sub.13H.sub.18N.sub.2O.sub.2
[1021] Calc MW: 306.37
[1022] MS (ESI) positive ion 307 (M+H).
Example 72
4-pyridin-4-yl-N--O-(2-thienyl)ethypenzamide
[1023] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.62 (d, 3H) 5.41-5.51 (m, 1H) 6.97-7.03 (m, 1H) 7.03-7.12 (m, 1H)
7.36-7.42 (m, 1H) 8.04-8.15 (m, 4H) 8.37 (d, 2H) 8.90 (d, 2H);
[1024] Formula: C.sub.18H.sub.16N.sub.2O S
[1025] Calc MW: 308.41
[1026] MS (ESI) positive ion 309 (M+H).
Example 73
4-pyridin-4-yl-N-[1-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)ethyl]benzamide
[1027] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.75 (d, 3H) 5.51 (q, 1H) 7.68-7.77 (m, 1H) 8.10-8.22 (m, 4H)
8.38-8.54 (m, 3H) 8.79-8.86 (m, 1H) 8.96 (d, 2H) 9.15-9.24 (m,
1H);
[1028] Formula: C.sub.21H.sub.17N.sub.5O.sub.2
[1029] Calc MW: 371.4
[1030] MS (ESI) positive ion 372 (M+H).
Example 74
N-{1-[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]ethyl}-4-pyridin-4-ylbenzami-
de
[1031] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.74 (d, 3H) 5.52 (q, 1H) 7.52-7.59 (m, 1 H) 7.59-7.64 (m, 1H)
7.67-7.74 (m, 1H) 7.88-7.94 (m, 1H) 8.07-8.15 (m, 4H) 8.29 (d, 2H)
8.89 (d, 2H);
[1032] Formula: C.sub.22H.sub.17ClN.sub.4O.sub.2
[1033] Calc MW: 404.86
[1034] MS (ESI) positive ion 405 (M+H).
Example 75
N-(1-phenylpropyl)-4-pyridin-4-ylbenzamide
[1035] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
0.93 (t, 3H) 1.78-1.94 (m, 2H) 4.88-4.99 (m, 1H) 7.21-7.29 (m, 1H)
7.33-7.39 (m, 2H) 7.39-7.45 (m, 2H) 8.05-8.16 (m, 4H) 8.39 (d, 2H)
8.92 (d, 2H);
[1036] Formula: C.sub.21H.sub.20N.sub.2O
[1037] Calc MW: 316.41
[1038] MS (ESI) positive ion 317 (M+H).
Example 76
4-pyridin-4-yl-N-(1-pyridin-2-ylethyl)benzamide
[1039] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.65 (d, 3H) 5.35 (q, 1H) 7.75-7.84 (m, 1H) 7.89-8.00 (m, 1H)
8.10-8.18 (m, 4H) 8.36-8.43 (m, 3H) 8.73-8.79 (m, 1H) 8.95 (d,
2H);
[1040] Formula: C.sub.13H.sub.17N.sub.3O
[1041] Calc MW: 303.37
[1042] MS (ESI) positive ion 304 (M+H).
Example 77
N-[1-(6-methylpyridin-2-yl)ethyl]-4-pyridin-4-ylbenzamide
[1043] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.54-1.69 (d, 3H) 2.70 (s, 3H) 5.32 (q, 1 H) 7.72 (d, 1H) 7.79 (d,
1H) 8.07-8.16 (m, 4H) 8.30-8.40 (m, 3H) 8.84-8.99 (m, 2 H);
[1044] Formula: C.sub.20H.sub.19N.sub.3O
[1045] Calc MW: 317.39
[1046] MS (ESI) positive ion 318 (M+H).
Example 78
N-[1-(5-methylpyridin-2-yl)ethyl]-4-pyridin-4-ylbenzamide
[1047] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.64 (d, 3H) 2.46 (s, 3H) 5.32 (q, 1H) 7.93 (d, 1H) 8.09-8.17 (m,
4H) 8.34 (d, 1H) 8.42 (d, 2H) 8.60-8.68 (m, 1H) 8.90-9.00 (m,
2H);
[1048] Formula: C.sub.20H.sub.19N.sub.3O
[1049] Calc MW: 317.39
[1050] MS (ESI) positive ion 318 (M+H).
Example 79
4-pyridin-4-yl-N-(1-pyridin-3-ylethyl)benzamide
[1051] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.62 (d, 3H) 5.35 (q, 1H) 8.01-8.09 (m, 1H) 8.10-8.17 (m, 4H)
8.37-8.43 (m, 2H) 8.57-8.68 (m, 1H) 8.77-8.84 (m, 1H) 8.91-9.01 (m,
3H);
[1052] Formula: C.sub.19H.sub.17N.sub.3O
[1053] Calc MW: 303.37
[1054] MS (ESI) positive ion 304 (M+H).
Example 80
4-pyridin-4-yl-N-[(1R)-1-pyridin-2-ylethyl]benzamide
[1055] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.65 (d, 3H) 5.34 (q, 1H) 7.74-7.85 (m, 1H) 7.92-7.99 (m, 1H)
8.10-8.21 (m, 4H) 8.37-8.45 (m, 3H) 8.73-8.79 (m, 1H) 8.95 (d,
2H);
[1056] Formula: C.sub.19H.sub.17N.sub.3O
[1057] Calc MW: 303.37
[1058] MS (ESI) positive ion 304 (M+H).
Example 81
N-[(1R)-1-(4-bromophenyl)ethyl]-4-pyridin-4-ylbenzamide
[1059] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.15 (q, 1H) 7.38 (d, 2H) 7.54 (d, 2H) 8.06-8.11 (m,
4H) 8.35 (d, 2H) 8.91 (d, 2H);
[1060] Formula: C.sub.20H.sub.17BrN.sub.2O
[1061] Calc MW: 381.28
[1062] MS (ESI) positive ion 381 (M+H).
Example 82
N-[(1R)-1-(4-methylphenyl)ethyl]-4-pyridin-4-ylbenzamide
[1063] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.49 (d, 3H) 2.28 (s, 3H) 5.16 (q, 1H) 7.15 (d, 2H) 7.30 (d, 2H)
8.05-8.11 (m, 4H) 8.34 (d, 2H) 8.90 (d, 2H);
[1064] Formula: C.sub.21H.sub.20N.sub.2O
[1065] Calc MW: 316.41
[1066] MS (ESI) positive ion 317 (M+H).
Example 83
N-[(1R)-1-(4-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide
[1067] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.49 (d, 3H) 3.72 (s, 3H) 5.15 (q, 1H) 6.92 (d, 2H) 7.34 (d, 2H)
8.04-8.13 (m, 4H) 8.34-8.41 (m, 2H) 8.88-8.96 (m, 2H);
[1068] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1069] Calc MW: 332.41
[1070] MS (ESI) positive ion 333 (M+H).
Example 84
N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide
[1071] .sup.1H NMR (300 MHz, DMSO-D6) .delta. ppm: 8.89 (d, J=8.1
Hz, 1H), 8.67 (d, J=6.1 Hz, 2 H), 8.03 (d, J=8.8 Hz, 2H), 7.92 (d,
J=8.8 Hz, 2H), 7.77 (d, J=6.1 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H),
6.95-7.00 (m, 2H), 6.80 (ddd, J=1.0, 2.4, 8.1 Hz, 1H), 5.16 (quin,
J=7.1 Hz, 1H), 3.74 (s, 3H), 1.48 (d, J=7.1 Hz, 3H)
[1072] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1073] Calc MW: 332.40
[1074] MS (ESI) positive ion 333 (M+H)
[1075] .alpha..sub.D.sup.20=-20.7 (c 1.0, methanol).
Example 85
N-[(1R)-1-(4-fluorophenyl)ethyl]-4-pyridin-4-ylbenzamide
[1076] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.20 (q, 1H) 7.11-7.22 (m, 2 H) 7.42-7.50 (m, 2H)
8.05-8.12 (m, 4H) 8.35 (d, 2H) 8.91 (d, 2H);
[1077] Formula: C.sub.20H.sub.17FN.sub.2O
[1078] Calc MW: 320.37
[1079] MS (ESI) positive ion 321 (M+H).
Example 86
4-pyridin-4-yl-N-{(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}benzamide
[1080] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.48 (q, 1H) 7.43-7.52 (m, 1H) 7.65-7.75 (m, 2H)
7.80-7.87 (m, 1H) 8.07-8.11 (m, 4H) 8.34 (d, 2H) 8.91 (d, 2 H);
[1081] Formula: C.sub.21H.sub.17F.sub.3N.sub.2O
[1082] Calc MW: 370.38
[1083] MS (ESI) positive ion 371 (M+H).
Example 87
4-pyridin-4-yl-N-{(1R)-1-[3-(trifluoromethyl)phenyl]ethyl}benzamide
[1084] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.55 (d, 3H) 5.28 (q, 1H) 7.58-7.65 (m, 2 H) 7.71-7.79 (m, 2H)
8.06-8.12 (m, 4H) 8.35 (d, 2H) 8.92 (d, 2H);
[1085] Formula: C.sub.21H.sub.17F.sub.3N.sub.2O
[1086] Calc MW: 370.38
[1087] MS (ESI) positive ion 371 (M+H).
Example 88
N-[(1R)-1-(2-fluorophenyl)ethyl]-4-pyridin-4-ylbenzamide
[1088] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.51 (d, 3H) 5.42 (q, 1H) 7.14-7.23 (m, 2H) 7.27-7.35 (m, 1H)
7.45-7.53 (m, 1H) 8.05-8.13 (m, 4H) 8.33 (d, 2H) 8.89 (d, 2H);
[1089] Formula: C.sub.20H.sub.17FN.sub.2O
[1090] Calc MW: 320.37
[1091] MS (ESI) positive ion 321 (M+H).
Example 89
N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-4-pyridin-4-ylbenzamide
[1092] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.58 (d, 3H) 5.35 (q, 1H) 7.97-8.03 (m, 1H) 8.05-8.10 (m, 4H)
8.10-8.13 (m, 2H) 8.19-8.24 (m, 2H) 8.84-8.89 (m, 2H);
[1093] Formula: C.sub.22H.sub.16F.sub.6N.sub.2O
[1094] Calc MW: 438.38
[1095] MS (ESI) positive ion 439 (M+H).
Example 90
N-[(1R)-1-(4-chlorophenyl)ethyl]-4-pyridin-4-ylbenzamide
[1096] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.50 (d, 3H) 5.17 (q, 1H) 7.37-7.47 (m, 4H) 8.06-8.11 (m, 4H) 8.33
(d, 2H) 8.90 (d, 2H);
[1097] Formula: C.sub.20H.sub.17ClN.sub.2O
[1098] Calc MW: 336.82
[1099] MS (ESI) positive ion 337 (M+H).
Example 91
N-[(1R)-1-(2-naphthyl)ethyl]-4-pyridin-4-ylbenzamide
[1100] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.62 (d, 3H) 5.36 (q, 1H) 7.46-7.55 (m, 2 H) 7.59-7.65 (m, 1H)
7.87-7.94 (m, 4H) 8.04-8.14 (m, 4H) 8.27 (d, 2H) 8.87 (d, 2 H);
[1101] Formula: C.sub.24H.sub.20N.sub.2O
[1102] Calc MW: 352.44
[1103] MS (ESI) positive ion 353 (M+H).
Example 92
N-[(1R)-2-(benzyloxy)-1-(hydroxymethyl)propyl]-4-pyridin-4-ylbenzamide
[1104] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm
1.13 (d, 3H) 3.57-3.69 (m, 2H) 3.79-3.88 (m, 1H) 4.05-4.19 (m, 1H)
4.35-4.66 (m, 2H) 7.16-7.52 (m, 5H) 7.72-7.81 (m, 2H) 7.86-8.06 (m,
4H) 8.47-8.78 (m, 2H);
[1105] Formula: C.sub.23H.sub.24N.sub.2O.sub.3
[1106] Calc MW: 376.46
[1107] MS (ESI) positive ion 377 (M+H); negative ion 375 (M-H).
Example 93
N-(3,4-dihydro-1H-isochromen-4-yl)-4-pyridin-4-ylbenzamide
[1108] Formula: C.sub.21H.sub.18N.sub.2O.sub.2
[1109] Calc MW: 330.39
Example 94
N--((R)-3-hydroxy-1-phenyl-propyl)-2-methoxy-4-pyridin-4-yl-benzamide
[1110] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 8.88 (d,
J=8.0, 1H), 8.68 (d, J=5.6, 2H), 7.80 (dd, J=1.6, 4.5, 2H), 7.78
(d, J=8.0, 1H), 7.50 (d, J=1.6, 1H), 7.45 (dd, J=1.6, 8.0, 1H),
7.40-7.29 (m, 4H), 7.26-7.20 (m, 1H), 5.19 (dd, J=7.3, 13.9, 1H),
4.69 (s, 1H), 4.03 (s, 3H), 3.45 (dd, J=5.5, 10.3, 2H), 2.04-1.85
(m, 2H).
[1111] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1112] Calc MW: 362.43
[1113] MS m/z: 363.18 [M+H].sup.+, Rt=1.84 min.
Example 95
N--[(S)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1114] A mixture of 4-(pyridin-4-yl)benzoic acid (0.970 g, 4.87
mmol), (S)-1-(3-methoxyphenyl)ethanamine (0.884 g, 5.84 mmol), DIEA
(1.7 ml, 9.8 mmol), and
O(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate
(1.87 g, 5.82 mmol) in DMF (10 ml) was stirred overnight, diluted
with EtOAc, washed with 1N NaOH, sat NaHCO.sub.3, and brine, dried
(Na.sub.2SO.sub.4), and chromatographed (20-85%
EtOAc/dichloromethane) and triturated (Et.sub.2O) to give the title
compound (1.075 g, 3.23 mmol) as a white solid.
[1115] .sup.1H NMR (300 MHz, DMSO-D.sub.6) .delta. ppm: 8.89 (d,
J=8.1 Hz, 1H), 8.67 (d, J=6.1 Hz, 2H), 8.03 (d, J=8.8 Hz, 2H), 7.92
(d, J=8.8 Hz, 2H), 7.77 (d, J=6.1 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H),
6.95-7.00 (m, 2H), 6.80 (ddd, J=1.0, 2.4, 8.1 Hz, 1H), 5.16 (quin,
J=7.1 Hz, 1H), 3.74 (s, 3H), 1.48 (d, J=7.1 Hz, 3H.
[1116] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1117] Calc MW: 332.40
[1118] MS (ESI) m/z: 333.0 [M+H].sup.+
[1119] .alpha..sub.D.sup.20=+22.4 (c 1.0, methanol).
Example 96
N--[(R)-1-(3-methoxy-phenyl)-ethyl]-2-methyl-4-pyridin-4-yl-benzamide
[1120] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1121] Calc MW: 346.43
Example 97
3-methoxy-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1122] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1123] Calc MW: 362.43
Example 98
N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-(2-methyl-pyridin-4-yl)-benzamide
[1124] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1125] Calc MW: 346.43
Example 99
4-(3-fluoro-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-benzamide
[1126] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1127] Calc MW: 350.39
Example 100
4-(2,6-dimethyl-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-benzamid-
e
[1128] Formula: C.sub.23H.sub.24N.sub.2O.sub.2
[1129] Calc MW: 360.45
Example 101
N--[(R)-1-(3-Methoxy-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1130] The synthesis of the title compound was performed as
described for example 7.
[1131] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.45-1.56 (m, 3H), 2.37-2.45 (s, 3H), 3.74-3.76 (s, 3H), 5.13-5.18
(m, 1H), 6.81-6.85 (m, 1H), 6.96-7.01 (m, 2H), 7.25-7.30 (m, 1H),
7.61-7.69 (m, 2H), 7.85-7.94 (m, 1H), 8.03-8.07 (m, 2H), 8.72-8.90
(m, 2H)
[1132] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1133] Calc MW: 346.43
[1134] MS (ESI) m/z: 347 [M+H].sup.+
[1135] The following compounds of Examples 102 to 104 were prepared
in an analogous method as described above
Example 102
N--[(S)-1-(3-methoxy-phenyl)-ethyl]-3-methyl-4-pyridin-4-yl-benzamide
[1136] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1137] Calc MW: 346.43
Example 103
2-methoxy-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1138] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1139] 1H NMR (400 MHz, DMSO) .delta. 8.67 (d, J=5.5, 2H), 8.53 (d,
J=8.0, 1H), 7.79 (d, J=5.8, 2H), 7.73 (d, J=7.9, 1H), 7.50 (s, 1H),
7.45 (d, J=8.0, 1H), 7.26 (t, J=7.6, 1H), 6.98 (d, J=7.1, 1H),
6.84-6.78 (m, 1H), 5.12 (p, J=7.1, 1H), 4.01 (s, 3H), 3.75 (d,
J=10.8, 3H), 1.45 (d, J=7.0, 3H).
Calc MW: 362.43
Example 104
N--[(S)-1-(3-methoxy-phenyl)-2-pyrrolidin-1-yl-ethyl]-4-pyridin-4-ylbenzam-
ide
[1140] Formula: C.sub.25H.sub.27N.sub.3O.sub.2
[1141] Calc MW: 401.51
Example 105
N-Indan-1-yl-2-methoxy-4-pyridin-4-yl-benzamide
[1142] To a solution of 2-methoxy-4-(pyridin-4-yl)benzoic acid (34
mg, 0.15 mmol), dissolved in DMA (0.5 ml) was added a solution of
HATU (68 mg, 0.18 mmol) dissolved in DMA (0.5 ml). Then a solution
of TEA (55 mg, 0.5 mmol), dissolved in DMA (0.4 ml) was added,
followed by a solution of 2,3-dihydro-1H-inden-1-amine (27 mg, 0.2
mmol) dissolved in DMA (0.7 ml). The resulting mixture was shaken
for 4 hours at room temperature. The reaction was checked by LC/MS
and concentrated to dryness. The residue was dissolved in 1:1
DMSO/methanol and purified by reverse phase HPLC (TFA method) to
afford the title compound.
[1143] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.88-2.00 (m, 1H), 2.46-2.52 (m, 1H), 2.82-3.02 (m, 2H), 3.98-4.03
(s, 3H), 5.53 (t, 1H), 7.23-7.34 (m, 4H), 7.62-7.68 (m, 2H),
7.85-7.89 (m, 1H), 8.37-8.43 (m, 2H), 8.90-8.94 (m, 2H)
[1144] Formula: C.sub.22H.sub.20N.sub.2O.sub.2
[1145] Calc MW: 344.41
[1146] MS (ESI) m/z: 345 [M+H].sup.+
[1147] The following compounds of the examples 106 to 147 were
prepared as described for example 105.
Example 106
2-methoxy-N--((R)-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1148] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.57-1.67 (m, 3H), 3.99-4.05 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70
(m, 6H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.95-8.01 (m, 1H),
8.20-8.24 (m, 1H), 8.33-8.37 (m, 2H), 8.86-8.91 (m, 2H)
[1149] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1150] Calc MW: 382.46
[1151] MS (ESI) m/z: 383 [M+H].sup.+
Example 107
2-methoxy-N--((R)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1152] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.54-1.61 (m, 3H), 4.04-4.09 (s, 3H), 5.28-5.33 (m, 1H), 7.47-7.67
(m, 5H), 7.77-7.82 (m, 1H), 7.87-7.95 (m, 4H), 8.34-8.39 (m, 2H),
8.87-8.91 (m, 2H)
[1153] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1154] Calc MW: 382.46
[1155] MS (ESI) m/z: 383 [M+H].sup.+
Example 108
N-((1S,2R)-2-hydroxy-1,2-diphenyl-ethyl)-2-methoxy-4-pyridin-4-ylbenzamide
[1156] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
4.00-4.08 (s, 3H), 4.98-5.03 (m, 1H), 5.22-5.36 (m, 1H), 7.19-7.32
(m, 10H), 7.58-7.68 (m, 2H), 7.81-7.88 (m, 1H), 8.32-8.40 (m, 2H),
8.88-8.95 (m, 2H)
[1157] Formula: C.sub.27H.sub.24N.sub.2O.sub.3
[1158] Calc MW: 424.50
[1159] MS (ESI) m/z: 425 [M+H].sup.+
Example 109
N-((1S,2R)-2-hydroxy-indan-1-yl)-2-methoxy-4-pyridin-4-yl-benzamide
[1160] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.85-2.93 (m, 1H), 3.13-3.23 (m, 1H), 4.01-4.07 (s, 3H), 4.51-4.59
(m, 1H), 5.40-5.46 (m, 1H), 7.18-7.30 (m, 4H), 7.66-7.73 (m, 2H),
8.21-8.27 (m, 1H), 8.33-8.41 (m, 2H), 8.87-8.94 (m, 2H)
[1161] Formula: C.sub.22H.sub.20N.sub.2O.sub.3
[1162] Calc MW: 360.41
[1163] MS (ESI) m/z: 361 [M+H].sup.+
Example 110
2-methoxy-N--((S)-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1164] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.59-1.64 (m, 3H), 3.99-4.03 (s, 3H), 5.89-5.98 (m, 1H), 7.52-7.68
(m, 6H), 7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.94-8.00 (m, 1H),
8.20-8.26 (m, 1H), 8.32-8.37 (m, 2H), 8.83-8.98 (m, 2H)
[1165] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1166] Calc MW: 382.46
[1167] MS (ESI) m/z: 383 [M+H].sup.+
Example 111
2-methoxy-4-pyridin-4-yl-N-(1,2,3,4-tetrahydro-naphthalen-1-yl)benzamide
[1168] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.77-2.06 (m, 4H), 2.72-2.85 (m, 2H), 3.93-4.02 (m, 3H), 5.13-5.31
(m, 1H), 7.12-7.23 (m, 3H), 7.30-7.36 (m, 1H), 7.58-7.66 (m, 2H),
7.81-7.95 (m, 1H), 8.26-8.43 (m, 2H), 8.83-8.92 (m, 2H)
[1169] Formula: C.sub.23H.sub.22N.sub.2O.sub.2
[1170] Calc MW: 358.44
[1171] MS (ESI) m/z: 359 [M+H].sup.+
Example 112
2-methoxy-N--((R)-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1172] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.45-1.50 (m, 3H), 4.00-4.06 (s, 3H), 5.11-5.18 (m, 1H), 7.25-7.44
(m, 5H), 7.58-7.65 (m, 2H), 7.77-7.83 (m, 1H), 8.26-8.38 (m, 2H),
8.81-8.97 (m, 2H)
[1173] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1174] Calc MW: 332.40
[1175] MS (ESI) m/z: 333 [M+H].sup.+
Example 113
N-((1R,2S)-2-hydroxy-indan-1-yl)-2-methoxy-4-pyridin-4-yl-benzamide
[1176] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.83-2.95 (m, 1H), 3.11-3.23 (m, 1H), 4.02-4.07 (s, 3H), 4.51-4.61
(m, 1H), 5.39-5.50 (m, 1H), 7.16-7.35 (m, 4H), 7.66-7.74 (m, 2H),
8.21-8.27 (m, 1H), 8.35-8.41 (m, 2H), 8.87-8.97 (m, 2H)
[1177] Formula: C.sub.22H.sub.20N.sub.2O.sub.3
[1178] Calc MW: 360.41
[1179] MS (ESI) m/z: 361 [M+H].sup.+
Example 114
2-methoxy-N--((S)-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1180] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.44-1.50 (m, 3H), 3.99-4.09 (s, 3H), 5.10-5.26 (m, 1H), 7.22-7.47
(m, 5H), 7.58-7.63 (m, 2H), 7.74-7.83 (m, 1H), 8.26-8.39 (m, 2H),
8.83-8.94 (m, 2H)
[1181] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1182] Calc MW: 332.40
[1183] MS (ESI) m/z: 333 [M+H].sup.+
Example 115
N-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-methoxy-4-pyridin-4-ylbenzamide
[1184] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
4.01-4.07 (m, 3H), 4.99-5.03 (m, 1H), 5.25-5.31 (m, 1H), 7.17-7.32
(m, 10H), 7.58-7.67 (m, 2H), 7.81-7.87 (m, 1H), 8.31-8.39 (m, 2H),
8.85-8.95 (m, 2H)
[1185] Formula: C.sub.27H.sub.24N.sub.2O.sub.3
[1186] Calc MW: 424.50
[1187] MS (ESI) m/z: 425 [M+H].sup.+
Example 116
2-methoxy-4-pyridin-4-yl-N--((R)-1-p-tolyl-ethyl)-benzamide
[1188] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.40-1.49 (m, 3H), 2.27-2.31 (s, 3H), 4.00-4.05 (s, 3H), 5.04-5.17
(m, 1H), 7.15-7.21 (m, 2H), 7.27-7.34 (m, 2H), 7.59-7.63 (m, 2H),
7.74-7.84 (m, 1H), 8.30-8.35 (m, 2H), 8.85-8.91 (m, 2H)
[1189] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1190] Calc MW: 346.43
[1191] MS (ESI) m/z: 347 [M+H].sup.+
Example 117
2-methoxy-4-pyridin-4-yl-N--((S)-1-p-tolyl-ethyl)-benzamide
[1192] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.42-1.47 (m, 3H), 2.25-2.32 (s, 3H), 4.00-4.06 (s, 3H), 5.06-5.13
(m, 1H), 7.15-7.20 (m, 2H), 7.27-7.33 (m, 2H), 7.59-7.65 (m, 2H),
7.77-7.80 (m, 1H), 8.31-8.36 (m, 2H), 8.85-8.93 (m, 2H)
[1193] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1194] Calc MW: 346.43
[1195] MS (ESI) m/z: 347 [M+H].sup.+
Example 118
N-((1R,2R)-2-hydroxy-indan-1-yl)-2-methoxy-4-pyridin-4-yl-benzamide
[1196] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.73-2.85 (m, 1H), 3.12-3.25 (m, 1H), 3.98-4.03 (s, 3H), 4.34-4.47
(m, 1H), 5.24-5.32 (m, 1H), 7.19-7.27 (m, 4H), 7.62-7.67 (m, 2H),
7.87-7.93 (m, 1H), 8.30-8.42 (m, 2H), 8.87-8.93 (m, 2H)
[1197] Formula: C.sub.22H.sub.20N.sub.2O.sub.3
[1198] Calc MW: 360.41
[1199] MS (ESI) m/z: 361 [M+H].sup.+
Example 119
N--[(R)-1-(4-chloro-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1200] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.42-1.52 (m, 3H), 3.98-4.05 (s, 3H), 5.01-5.19 (m, 1H), 7.35-7.50
(m, 4H), 7.59-7.67 (m, 2H), 7.73-7.81 (m, 1H), 8.31-8.43 (m, 2H),
8.85-9.00 (m, 2H)
[1201] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1202] Calc MW: 366.85
[1203] MS (ESI) m/z: 367 [M+H].sup.+
Example 120
N--[(S)-1-(4-chloro-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1204] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.41-1.51 (m, 3H), 4.01-4.05 (s, 3H), 5.08-5.16 (m, 1H), 7.39-7.47
(m, 4H), 7.59-7.67 (m, 2H), 7.73-7.80 (m, 1H), 8.30-8.40 (m, 2H),
8.84-8.95 (m, 2H)
[1205] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1206] Calc MW: 366.85
[1207] MS (ESI) m/z: 367 [M+H].sup.+
Example 121
2-methoxy-N--((S)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1208] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.52-1.61 (m, 3H), 4.03-4.08 (s, 3H), 5.28-5.37 (m, 1H), 7.47-7.67
(m, 5H), 7.77-7.82 (m, 1H), 7.88-7.97 (m, 4H), 8.33-8.38 (m, 2H),
8.86-8.94 (m, 2H)
[1209] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1210] Calc MW: 382.46
[1211] MS (ESI) m/z: 383 [M+H].sup.+
Example 122
N-[1-(3-chloro-4-methoxy-phenyl)-2-hydroxy-ethyl]-2-methoxy-4-pyridin-4-yl-
-benzamide
[1212] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.66-3.71 (m, 2H), 3.84-3.86 (s, 3H), 4.05-4.10 (s, 3H), 4.94-5.06
(m, 1H), 7.07-7.18 (m, 1H), 7.29-7.37 (m, 1H), 7.44-7.47 (m, 1H),
7.62-7.71 (m, 2H), 7.85-7.89 (m, 1H), 8.32-8.42 (m, 2H), 8.88-8.94
(m, 2H)
[1213] Formula: C.sub.22H.sub.21ClN.sub.2O.sub.4
[1214] Calc MW: 412.87
[1215] MS (ESI) m/z: 413 [M+H].sup.+
Example 123
N-[1-(3,4-dimethyl-phenyl)-2-hydroxy-ethyl]-2-methoxy-4-pyridin-4-ylbenzam-
ide
[1216] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.24-2.32 (m, 6H), 3.55-3.69 (m, 2H), 4.05-4.11 (s, 3H), 5.28-5.41
(m, 1H), 7.05-7.10 (m, 2H), 7.18-7.23 (m, 1H), 7.59-7.69 (m, 2H),
7.84-7.91 (m, 1H), 8.32-8.42 (m, 2H), 8.84-8.94 (m, 2H)
[1217] Formula: C.sub.23H.sub.24N.sub.2O.sub.3
[1218] Calc MW: 376.45
[1219] MS (ESI) m/z: 377 [M+H].sup.+
Example 124
N-[2-hydroxy-1-(4-isopropyl-phenyl)-ethyl]-2-methoxy-4-pyridin-4-ylbenzami-
de
[1220] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.16-1.21 (m, 6H), 2.82-2.91 (m, 1H), 3.64-3.75 (m, 2H), 4.05-4.12
(s, 3H), 5.02-5.08 (m, 1H), 7.20-7.33 (m, 4H), 7.62-7.69 (m, 2H),
7.90-7.95 (m, 1H), 8.34-8.41 (m, 2H), 8.82-8.96 (m, 2H)
[1221] Formula: C.sub.24H.sub.26N.sub.2O.sub.3
[1222] Calc MW: 390.48
[1223] MS (ESI) m/z: 391 [M+H].sup.+
Example 125
2-methoxy-N--[(R)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1224] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.34-1.47 (m, 3H), 3.87-3.92 (s, 3H), 4.05-4.10 (s, 3H), 5.33-5.43
(m, 1H), 6.89-7.07 (m, 2H), 7.23-7.40 (m, 2H), 7.62-7.70 (m, 2H),
7.88-7.97 (m, 1H), 8.35-8.44 (m, 2H), 8.87-8.98 (m, 2H)
[1225] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1226] Calc MW: 362.43
[1227] MS (ESI) m/z: 363 [M+H].sup.+
Example 126
N--[(S)-1-(3,4-difluoro-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1228] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.44-1.47 (m, 3H), 4.01-4.05 (s, 3H), 5.09-5.17 (m, 1H), 7.23-7.30
(m, 1H), 7.37-7.52 (m, 2H), 7.58-7.66 (m, 2H), 7.71-7.80 (m, 1H),
8.27-8.39 (m, 2H), 8.79-9.05 (m, 2H)
[1229] Formula: C.sub.21H.sub.18F.sub.2N.sub.2O.sub.2
[1230] Calc MW: 368.38
[1231] MS (ESI) m/z: 369 [M+H].sup.+
Example 127
N--[(S)-1-(4-fluoro-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1232] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.44-1.50 (m, 3H), 3.99-4.04 (s, 3H), 5.08-5.21 (m, 1H), 7.14-7.25
(m, 2H), 7.43-7.50 (m, 2H), 7.59-7.65 (m, 2H), 7.74-7.80 (m, 1H),
8.31-8.38 (m, 2H), 8.86-8.93 (m, 2H)
[1233] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1234] Calc MW: 350.39
[1235] MS (ESI) m/z: 351 [M+H].sup.+
Example 128
2-methoxy-N--[(R)-1-(4-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1236] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.42-1.48 (m, 3H), 3.73-3.75 (s, 3H), 3.99-4.06 (s, 3H), 5.05-5.15
(m, 1H), 6.90-6.96 (m, 2H), 7.31-7.38 (m, 2H), 7.59-7.65 (m, 2H),
7.75-7.85 (m, 1H), 8.28-8.38 (m, 2H), 8.81-8.95 (m, 2H)
[1237] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1238] Calc MW: 362.43
[1239] MS (ESI) m/z: 363 [M+H].sup.+
Example 129
2-methoxy-N-[1-(4-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1240] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.40-1.47 (m, 3H), 3.74-3.76 (s, 3H), 3.99-4.04 (s, 3H), 5.08-5.14
(m, 1H), 6.90-6.98 (m, 2H), 7.31-7.36 (m, 2H), 7.58-7.64 (m, 2H),
7.75-7.82 (m, 1H), 8.32-8.39 (m, 2H), 8.85-8.96 (m, 2H)
[1241] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1242] Calc MW: 362.43
[1243] MS (ESI) m/z: 363 [M+H].sup.+
Example 130
2-methoxy-N--[(S)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1244] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.40-1.52 (m, 3H), 3.76-3.78 (s, 3H), 4.01-4.06 (s, 3H), 5.06-5.16
(m, 1H), 6.78-6.87 (m, 1H), 6.94-7.04 (m, 2H), 7.24-7.37 (m, 1H),
7.62-7.66 (m, 2H), 7.74-7.81 (m, 1H), 8.36-8.44 (m, 2H), 8.88-8.97
(m, 2H)
[1245] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1246] Calc MW: 362.43
[1247] MS (ESI) m/z: 363 [M+H].sup.+
Example 131
N--[(R)-1-(4-fluoro-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1248] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.42-1.49 (m, 3H), 4.00-4.05 (m, 3H), 5.08-5.18 (m, 1H), 7.15-7.23
(m, 2H), 7.42-7.48 (m, 2H), 7.57-7.63 (m, 2H), 7.74-7.82 (m, 1H),
8.24-8.37 (m, 2H), 8.82-8.92 (m, 2H)
[1249] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1250] Calc MW: 350.39
[1251] MS (ESI) m/z: 349 [M-H].sup.-
Example 132
2-methoxy-4-pyridin-4-yl-N--[(R)-1-(3-trifluoromethyl-phenyl)-ethyl]-benza-
mide
[1252] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.42-1.54 (m, 3H), 4.00-4.09 (s, 3H), 5.16-5.35 (m, 1H), 7.59-7.87
(m, 7H), 8.30-8.45 (m, 2H), 8.86-9.07 (m, 2H)
[1253] Formula: C.sub.22H.sub.19F.sub.3N.sub.2O.sub.2
[1254] Calc MW: 400.40
[1255] MS (ESI) m/z: 401 [M+H].sup.+
Example 133
N-[1-(3,4-diethoxy-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1256] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.25-1.41 (m, 6H), 1.41-1.48 (m, 3H), 3.93-4.11 (m, 7H), 5.04-5.14
(m, 1H), 6.86-6.95 (m, 2H), 6.98-7.11 (m, 1H), 7.56-7.66 (m, 2H),
7.71-7.85 (m, 1H), 8.24-8.42 (m, 2H), 8.79-8.98 (m, 2H)
[1257] Formula: C.sub.25H.sub.28N.sub.2O.sub.4
[1258] Calc MW: 420.51
[1259] MS (ESI) m/z: 421 [M+H].sup.+
Example 134
N-[1-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-ethyl]-2-methoxy-4-pyridin-4-ylbe-
nzamide
[1260] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.36-1.50 (m, 3H), 3.99-4.08 (s, 3H), 4.15-4.28 (m, 4H), 4.96-5.14
(m, 1H), 6.78-6.99 (m, 3H), 7.58-7.68 (m, 2H), 7.72-7.82 (m, 1H),
8.31-8.42 (m, 2H), 8.84-8.95 (m, 2H)
[1261] Formula: C.sub.23H.sub.22N.sub.2O.sub.4
[1262] Calc MW: 390.44
[1263] MS (ESI) m/z: 391 [M+H].sup.+
Example 135
N-[1-(3,5-dichloro-phenyl)-2-hydroxy-ethyl]-2-methoxy-4-pyridin-4-ylbenzam-
ide
[1264] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.68-3.75 (m, 2H), 4.07-4.12 (s, 3H), 5.02-5.09 (m, 1H), 7.44-7.51
(m, 3H), 7.60-7.70 (m, 2H), 7.80-7.90 (m, 1H), 8.28-8.42 (m, 2H),
8.86-8.95 (m, 2H)
[1265] Formula: C.sub.21H.sub.18Cl.sub.2N.sub.2O.sub.3
[1266] Calc MW: 417.29
[1267] MS (ESI) m/z: 417 [M+H].sup.+
Example 136
N-[2-hydroxy-1-(4-methylsulfanyl-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-b-
enzamide
[1268] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.43-2.48 (s, 3H), 3.62-3.75 (m, 2H), 4.05-4.11 (s, 3H), 5.00-5.07
(m, 1H), 7.23-7.39 (m, 4H), 7.63-7.72 (m, 2H), 7.89-7.94 (m, 1H),
8.38-8.45 (m, 2H), 8.90-8.97 (m, 2H)
[1269] Formula: C.sub.22H.sub.22N.sub.2O.sub.3S
[1270] Calc MW: 394.49
[1271] MS (ESI) m/z: 395 [M+H].sup.+
Example 137
N-[2-hydroxy-1-(4-isopropoxy-phenyl)-ethyl]-2-methoxy-4-pyridin-4-ylbenzam-
ide
[1272] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.22-1.28 (m, 6H), 3.62-3.72 (m, 2H), 4.05-4.10 (s, 3H), 4.54-4.59
(m, 1H), 4.97-5.04 (m, 1H), 6.86-6.94 (m, 2H), 7.26-7.31 (m, 2H),
7.61-7.68 (m, 2H), 7.88-7.96 (m, 1H), 8.29-8.39 (m, 2H), 8.85-8.93
(m, 2H)
[1273] Formula: C.sub.24H.sub.26N.sub.2O.sub.4
[1274] Calc MW: 406.48
[1275] MS (ESI) m/z: 407 [M+H].sup.+
Example 138
2-methoxy-N--[(S)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1276] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.37-1.44 (m, 3H), 3.86-3.98 (s, 3H), 4.06-4.10 (s, 3H), 5.36-5.42
(m, 1H), 6.90-7.12 (m, 2H), 7.23-7.37 (m, 2H), 7.57-7.69 (m, 2H),
7.88-7.94 (m, 1H), 8.27-8.38 (m, 2H), 8.84-8.93 (m, 2H)
[1277] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1278] Calc MW: 362.43
[1279] MS (ESI) m/z: 363 [M+H].sup.+
Example 139
N-(2-hydroxy-1-p-tolyl-ethyl)-2-methoxy-4-pyridin-4-yl-benzamide
[1280] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.25-2.33 (s, 3H), 3.61-3.72 (m, 2H), 4.03-4.12 (s, 3H), 4.96-5.07
(m, 1H), 7.12-7.34 (m, 4H), 7.58-7.72 (m, 2H), 7.87-7.96 (m, 1H),
8.30-8.40 (m, 2H), 8.80-8.98 (m, 2H)
[1281] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1282] Calc MW: 362.43
[1283] MS (ESI) m/z: 363 [M+H].sup.+
Example 140
N-(2-hydroxy-1-naphthalen-1-yl-ethyl)-2-methoxy-4-pyridin-4-ylbenzamide
[1284] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.74-3.80 (m, 1H), 3.86-3.93 (m, 1H), 4.08-4.13 (s, 3H), 5.88-5.96
(m, 1H), 7.50-7.71 (m, 6H), 7.85-8.02 (m, 3H), 8.25-8.30 (m, 1H),
8.35-8.41 (m, 2H), 8.87-8.95 (m, 2H)
[1285] Formula: C.sub.25H.sub.22N.sub.2O.sub.3
[1286] Calc MW: 398.46
[1287] MS (ESI) m/z: 399 [M+H].sup.+
Example 141
N-[1-(2,4-dimethyl-phenyl)-2-hydroxy-ethyl]-2-methoxy-4-pyridin-4-ylbenzam-
ide
[1288] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.22-2.27 (m, 3H), 2.36-2.40 (s, 3H), 3.55-3.67 (m, 2H), 4.04-4.11
(s, 3H), 5.18-5.28 (m, 1H), 6.92-7.05 (m, 2H), 7.16-7.28 (m, 1H),
7.58-7.71 (m, 2H), 7.85-7.92 (m, 1H), 8.33-8.39 (m, 2H), 8.78-9.02
(m, 2H)
[1289] Formula: C.sub.23H.sub.24N.sub.2O.sub.3
[1290] Calc MW: 376.45
[1291] MS (ESI) m/z: 377 [M+H].sup.+
Example 142
N-[2-hydroxy-1-(2-methoxy-phenyl)-ethyl]-2-methoxy-4-pyridin-4-ylbenzamide
[1292] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.58-3.71 (m, 2H), 3.87-3.89 (s, 3H), 4.10-4.13 (s, 3H), 5.32-5.42
(m, 1H), 6.91-7.08 (m, 2H), 7.19-7.33 (m, 2H), 7.61-7.74 (m, 2H),
7.95-8.04 (m, 1H), 8.35-8.44 (m, 2H), 8.80-9.01 (m, 2H)
[1293] Formula: C.sub.22H.sub.22N.sub.2O.sub.4
[1294] Calc MW: 378.43
[1295] MS (ESI) m/z: 379 [M+H].sup.+
Example 143
N-[2-hydroxy-1-(4-methoxy-naphthalen-1-yl)-ethyl]-2-methoxy-4-pyridin-4-yl-
-benzamide
[1296] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.70-3.78 (m, 1H), 3.83-3.90 (m, 1H), 3.95-3.98 (s, 3H), 4.07-4.11
(s, 3H), 5.79-5.89 (m, 1H), 6.94-7.05 (m, 1H), 7.49-7.71 (m, 5H),
7.88-7.97 (m, 1H), 8.18-8.27 (m, 2H), 8.34-8.43 (m, 2H), 8.87-8.96
(m, 2H)
[1297] Formula: C.sub.26H.sub.24N.sub.2O.sub.4
[1298] Calc MW: 428.49
[1299] MS (ESI) m/z: 429 [M+H].sup.+
Example 144
N-[1-(4-benzyloxy-phenyl)-2-hydroxy-ethyl]-2-methoxy-4-pyridin-4-ylbenzami-
de
[1300] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.59-3.73 (m, 2H), 4.04-4.09 (s, 3H), 4.98-5.04 (m, 1H), 5.07-5.11
(s, 2H), 6.90-7.04 (m, 2H), 7.27-7.50 (m, 7H), 7.60-7.68 (m, 2H),
7.89-7.95 (m, 1H), 8.28-8.40 (m, 2H), 8.85-8.94 (m, 2H)
Formula: C.sub.28H.sub.26N.sub.2O.sub.4
[1301] Calc MW: 454.52
[1302] MS (ESI) m/z: 455 [M+H].sup.+
Example 145
N--[(R)-1-(4-bromo-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1303] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.38-1.51 (m, 3H), 3.99-4.05 (s, 3H), 5.02-5.23 (m, 1H), 7.34-7.81
(m, 7H), 8.30-8.39 (m, 2H), 8.85-8.98 (m, 2H)
[1304] Formula: C.sub.21H.sub.19BrN.sub.2O.sub.2
[1305] Calc MW: 411.30
[1306] MS (ESI) m/z: 409 [M-H].sup.-
Example 146
N--[(S)-1-(4-bromo-phenyl)-ethyl]-2-methoxy-4-pyridin-4-yl-benzamide
[1307] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.40-1.49 (m, 3H), 4.00-4.04 (s, 3H), 5.06-5.15 (m, 1H), 7.36-7.43
(m, 2H), 7.52-7.66 (m, 4H), 7.74-7.78 (m, 1H), 8.32-8.38 (m, 2H),
8.85-8.98 (m, 2H)
[1308] Formula: C.sub.21H.sub.19BrN.sub.2O.sub.2
[1309] Calc MW: 411.30
[1310] MS (ESI) m/z: 411 [M+H].sup.+
Example 147
N-((1S,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-methoxy-4-pyridin-4-ylbenzamide
[1311] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
4.01-4.10 (s, 3H), 4.96-5.06 (m, 1H), 5.23-5.34 (m, 1H), 7.16-7.38
(m, 10H), 7.57-7.65 (m, 2H), 7.82-7.87 (m, 1H), 8.26-8.32 (m, 2H),
8.81-8.94 (m, 2H)
[1312] Formula: C.sub.27H.sub.24N.sub.2O.sub.3
[1313] Calc MW: 424.50
[1314] MS (ESI) m/z: 425 [M+H].sup.+
Example 148
N--((S)-3-hydroxy-1-phenyl-propyl)-4-pyridin-4-yl-benzamide
[1315] The synthesis of the title compound was performed as
described for example 1.
[1316] .sup.1H NMR (400 MHz, DMSO-d.sub.6): 8.84 (d, 1H), 8.66 (d,
2H), 8.01 (d, 2H), 7.90 (d, 2H), 7.75 (d, 2h), 7.40 (d 2H), 7.31
(dd, 2H), 7.21 (dd, 1H), 5.22-5.14 (m, 1H), 4.55 (t, 1H), 3.52-3.39
(m, 2H), 2.12-2.02 (m, 1H), 1.97-1.88 (m, 1H).
[1317] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1318] Calc MW: 332.40
[1319] MS (ESI) m/z: 333.1 [M+H].sup.+
Example 149
N-[1-(3-methoxy-phenyl)-2-pyrrolidin-1-yl-ethyl]-4-pyridin-4-yl-benzamide
[1320] The synthesis of the title compound was performed as
described for example 1.
[1321] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 1.65 (t,
4H), 2.49-2.53 (m, 4H, overly with DMSO signal), 2.61 (dd, 1H),
2.98 (dd, 1H), 3.74 (s, 3H), 5.13-5.19 (m, 1H), 6.80 (dd, 1H), 6.98
(d, 1H), 6.99-7.05 (m, 1H), 7.23 (dd, 1H), 7.75 (d, 2H), 7.91 (d,
2H), 8.01 (d, 2H), 8.66 (d, 2H), 8.81 (d, 1H);
[1322] Formula: C.sub.25H.sub.27N.sub.3O.sub.2
[1323] Calc MW: 401.51
[1324] MS (ESI) m/z: 425 [M+H].sup.+
Example 150
N-[1-(3-propoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1325] The synthesis of the title compound was performed as
described for example 1.
[1326] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 0.97 (t,
3H),1.48 (d, 3H), 1.71 (sext, 2H), 3.90 (t, 2H), 5.16 (quint, 1H),
6.77 (dd, 1H), 6.95 (d, 1H), 6.96 (s, 1H), 7.21 (t, 1H) 7.76 (d,
2H) 7.91 (d, 2H) 8.02 (d, 2H) 8.66 (d, 2H) 8.88 (d, 1H)
[1327] Formula: C.sub.23H.sub.24N.sub.2O.sub.2
[1328] Calc MW: 360.45
[1329] MS (ESI) m/z: 361.2 [M+H].sup.+
Example 151
N-[1-(3-benzyloxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1330] The synthesis of the title compound was performed as
described for example 1.
[1331] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 1.48 (d,
3H), 5.08 (s, 2H), 5.17 (quint, 1H), 6.87 (dd, 1H), 6.97 (d, 1H),
7.06 (s, 1H), 7.24 (t, 1H), 7.31 (dd, 1H), 7.36 (t, 2H), 7.44 (d,
2H) 7.76 (d, 2H) 7.91 (d, 2H) 8.02 (d, 2H) 8.66 (d, 2H) 8.88 (d,
1H)
[1332] Formula: C.sub.27H.sub.24N.sub.2O.sub.2
[1333] Calc MW: 408.50
[1334] MS (ESI) m/z: 409 [M+H].sup.+
Example 152
N-[1-(3-isopropoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1335] The synthesis of the title compound was performed as
described for example 1.
[1336] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.24 (d, 3H), 1.26 (d, 3H), 1.48 (d, 3H), 4.58 (sept, 1H), 5.15
(quint, 1H), 6.76 (dd, 1H), 6.92 (d, 1H), 6.93 (s, 1H), 7.20 (t,
1H), 7.76 (d, 2H), 7.91 (d, 2H), 8.02 (d, 2H), 8.66 (d, 2H) 8.88
(d, 1H)
[1337] Formula: C.sub.23H.sub.24N.sub.2O.sub.2
[1338] Calc MW: 360.45
[1339] MS (ESI) m/z: 361.2 [M+H].sup.+
Example 153
N-[1-(3-isobutoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1340] The synthesis of the title compound was performed as
described for example 1.
[1341] .sup.1H NMR (400 MHz, DMSO-D.sub.6) ppm: ppm 0.97 (d, 6H),
1.48 (d, 3H), 2.00 (sept, 1H), 3.72 (d, 2H), 5.15 (quint, 1H), 6.77
(dd, 1H), 6.95 (d, 1H), 6.96 (s, 1H), 7.21 (t, 1H), 7.75 (d, 2H),
7.91 (d, 2H), 8.02 (d, 2H), 8.66 (d, 2H) 8.88 (d, 1H)
[1342] Formula: C.sub.24H.sub.26N.sub.2O.sub.2
[1343] Calc MW: 374.48
[1344] MS (ESI) m/z: 375 [M+H].sup.++
Example 154
N-Indan-1-yl-4-pyridin-4-yl-benzamide
[1345] The synthesis of the title compound was performed as
described for example 7.
[1346] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.95-2.12 (m, 1H), 2.45-2.52 (m, 1H), 2.82-3.06 (m, 2H), 5.47-5.69
(m, 1H), 7.07-7.45 (m, 4H), 8.05-8.17 (m, 4H), 8.28-8.41 (m, 2H),
8.85-8.95 (m, 2H)
[1347] Formula: C.sub.21H.sub.18N.sub.2O
[1348] Calc MW: 314.39
[1349] MS (ESI) m/z: 315 [M+H].sup.+
[1350] The compounds of Example 155 and 156 were prepared in an
analogous method as described above.
Example 155
4-(2-fluoro-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-benzamide
[1351] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 1.48 (d,
3H) 3.7 (s, 3H) 5.16 (m, 1H) 6.8 (ddd, 1H) 6.97 (dd, 2H) 7.24 (t,
1H) 7.62 (s, 1H) 7.77 (m, 1H) 8.0 (m, 4H) 8.34 (d, 1H) 8.9 (d,
1H).
[1352] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1353] Calc MW: 350.39
[1354] MS (ESI) positive ion: 351 [M+H].sup.+
Example 156
3-Chloro-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1355] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1356] Calc MW: 366.85
[1357] The following compounds of the Examples 157 to 186 were
prepared as described for example 7.
Example 157
4-(3-methyl-pyridin-4-yl)-N--((R)-1-phenyl-ethyl)-benzamide
[1358] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48-1.56 (m, 3H), 2.37-2.44 (s, 3H), 5.10-5.34 (m, 1H), 7.21-7.48
(m, 5H), 7.61-7.69 (m, 2H), 7.86-7.93 (m, 1H), 7.99-8.09 (m, 2H),
8.75-8.81 (m, 1H), 8.83-8.89 (m, 1H)
[1359] Formula: C.sub.21H.sub.20N.sub.2O
[1360] Calc MW: 316.40
[1361] MS (ESI) m/z: 317 [M+H].sup.+
Example 158
4-(3-methyl-pyridin-4-yl)-N--((S)-1-phenyl-ethyl)-benzamide
[1362] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) ppm: 1.49-1.54
(m, 3H), 2.41-2.44 (s, 3H), 5.15-5.23 (m, 1H), 7.22-7.50 (m, 5H),
7.61-7.70 (m, 2H), 7.88-7.94 (m, 1H), 8.02-8.10 (m, 2H), 8.75-8.81
(m, 1H), 8.83-8.88 (m, 1H)
[1363] Formula: C.sub.21H.sub.20N.sub.2O
[1364] Calc MW: 316.40
[1365] MS (ESI) m/z: 317 [M+H].sup.+
Example 159
4-(3-methyl-pyridin-4-yl)-N--((R)-1-naphthalen-1-yl-ethyl)-benzamide
[1366] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.61-1.69 (m, 3H), 2.37-2.46 (s, 3H), 5.95-6.02 (m, 1H), 7.47-7.71
(m, 6H), 7.82-8.10 (m, 5H), 8.19-8.28 (m, 1H), 8.74-8.81 (m, 1H),
8.82-8.89 (m, 1H)
[1367] Formula: C.sub.25H.sub.22N.sub.2O
[1368] Calc MW: 366.46
[1369] MS (ESI) m/z: 367 [M+H].sup.+
Example 160
4-(3-methyl-pyridin-4-yl)-N-(1,2,3,4-tetrahydro-naphthalen-1-yl)-benzamide
[1370] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.71-2.06 (m, 4H), 2.39-2.46 (s, 3H), 2.67-2.90 (m, 2H), 5.13-5.42
(m, 1H), 7.12-7.23 (m, 4H), 7.62-7.68 (m, 2H), 7.85-7.91 (m, 1H),
8.04-8.10 (m, 2H), 8.74-8.81 (m, 1H), 8.82-8.88 (m, 1H)
[1371] Formula: C.sub.23H.sub.22N.sub.2O
[1372] Calc MW: 342.44
[1373] MS (ESI) m/z: 343 [M+H].sup.+
Example 161
N-((1R,25)-2-hydroxy-1,2-diphenyl-ethyl)-4-(3-methyl-pyridin-4-yl)-benzami-
de
[1374] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.34-2.38 (s, 3H), 4.92-4.97 (m, 1H), 5.15-5.23 (m, 1H), 7.17-7.40
(m, 6H), 7.44-7.59 (m, 6H), 7.76-7.82 (m, 3H), 8.66-8.85 (m,
2H)
[1375] Formula: C.sub.27H.sub.24N.sub.2O.sub.2
[1376] Calc MW: 408.50
[1377] MS (ESI) m/z: 409 [M+H].sup.+
Example 162
N-((1S,2R)-2-hydroxy-1,2-diphenyl-ethyl)-4-(3-methyl-pyridin-4-yl)-benzami-
de
[1378] The synthesis of the title compound was performed as
described for example 7.
[1379] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.33-2.39 (s, 3H), 4.91-4.98 (m, 1H), 5.15-5.25 (m, 1H), 7.18-7.38
(m, 6H), 7.44-7.60 (m, 6H), 7.71-7.89 (m, 3H), 8.61-8.90 (m,
2H)
[1380] Formula: C.sub.27H.sub.24N.sub.2O.sub.2
[1381] Calc MW: 408.50
[1382] MS (ESI) m/z: 409 [M+H].sup.+
Example 163
4-(3-methyl-pyridin-4-yl)-N--((R)-1-p-tolyl-ethyl)-benzamide
[1383] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.46-1.52 (m, 3H), 2.24-2.30 (s, 3H), 2.40-2.44 (s, 3H), 5.10-5.23
(m, 1H), 7.12-7.18 (m, 2H), 7.27-7.33 (m, 2H), 7.63-7.67 (m, 2H),
7.89-7.95 (m, 1H), 8.02-8.08 (m, 2H), 8.72-8.89 (m, 2H)
[1384] Formula: C.sub.22H.sub.22N.sub.2O
[1385] Calc MW: 330.43
[1386] MS (ESI) m/z: 331 [M+H].sup.+
Example 164
4-(3-methyl-pyridin-4-yl)-N--((S)-1-p-tolyl-ethyl)-benzamide
[1387] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.47-1.51 (m, 3H), 2.26-2.29 (s, 3H), 2.41-2.45 (s, 3H), 5.08-5.25
(m, 1H), 7.10-7.19 (m, 2H), 7.25-7.35 (m, 2H), 7.60-7.72 (m, 2H),
7.87-7.96 (m, 1H), 8.01-8.08 (m, 2H), 8.69-8.84 (m, 1H), 8.82-8.98
(m, 1H)
[1388] Formula: C.sub.22H.sub.22N.sub.2O
[1389] Calc MW: 330.43
[1390] MS (ESI) m/z: 331 [M+H].sup.+
Example 165
N-indan-1-yl-4-(3-methyl-pyridin-4-yl)-benzamide
[1391] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.98-2.08 (m, 1H), 2.40-2.44 (s, 3H), 2.46-2.51 (m, 1H), 2.84-3.09
(m, 2H), 5.52-5.65 (m, 1H), 7.17-7.33 (m, 4H), 7.62-7.69 (m, 2H),
7.85-7.91 (m, 1H), 8.05-8.11 (m, 2H), 8.74-8.77 (m, 1H), 8.81-8.85
(m, 1H)
[1392] Formula: C.sub.22H.sub.20N.sub.2O
[1393] Calc MW: 328.41
[1394] MS (ESI) m/z: 329 [M+H].sup.+
Example 166
N--[(R)-1-(4-bromo-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1395] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48-1.52 (m, 3H), 2.39-2.44 (s, 3H), 5.10-5.18 (m, 1H), 7.32-7.43
(m, 2H), 7.51-7.55 (m, 2H), 7.62-7.72 (m, 2H), 7.85-7.94 (m, 1H),
8.02-8.07 (m, 2H), 8.57-9.27 (m, 2H)
[1396] Formula: C.sub.21H.sub.19BrN.sub.2O
[1397] Calc MW: 395.30
[1398] MS (ESI) m/z: 396 [M+H].sup.+
Example 167
N--[(S)-1-(4-bromo-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1399] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.47-1.55 (m, 3H), 2.38-2.45 (s, 3H), 5.10-5.21 (m, 1H), 7.37-7.40
(m, 2H), 7.52-7.56 (m, 2H), 7.63-7.71 (m, 2H), 7.86-7.94 (m, 1H),
8.03-8.07 (m, 2H), 8.74-8.88 (m, 2H)
[1400] Formula: C.sub.21H.sub.19BrN.sub.2O
[1401] Calc MW: 395.30
[1402] MS (ESI) m/z: 396 [M+H].sup.+
Example 168
N--[(R)-1-(4-chloro-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1403] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.49-1.52 (m, 3H), 2.38-2.46 (s, 3H), 5.12-5.22 (m, 1H), 7.39-7.48
(m, 4H), 7.63-7.67 (m, 2H), 7.86-7.94 (m, 1H), 8.02-8.09 (m, 2H),
8.69-9.00 (m, 2H)
[1404] Formula: C.sub.21H.sub.19ClN.sub.2O
[1405] Calc MW: 350.85
[1406] MS (ESI) m/z: 351 [M+H].sup.+
Example 169
N--[(S)-1-(4-chloro-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1407] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.41-1.60 (m, 3H), 2.30-2.48 (s, 3H), 5.04-5.30 (m, 1H), 7.33-7.50
(m, 4H), 7.59-7.72 (m, 2H), 7.85-7.94 (m, 1H), 8.01-8.13 (m, 2H),
8.66-8.89 (m, 2H)
[1408] Formula: C.sub.21H.sub.19ClN.sub.2O
[1409] Calc MW: 350.85
[1410] MS (ESI) m/z: 351 [M+H].sup.+
Example 170
4-(3-methyl-pyridin-4-yl)-N--((R)-1-naphthalen-2-yl-ethyl)-benzamide
[1411] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.58-1.64 (m, 3H), 2.37-2.44 (s, 3H), 5.33-5.41 (m, 1H), 7.46-7.70
(m, 5H), 7.85-7.94 (m, 5H), 8.06-8.12 (m, 2H), 8.76-8.91 (m,
2H)
[1412] Formula: C.sub.25H.sub.22N.sub.2O
[1413] Calc MW: 366.46
[1414] MS (ESI) m/z: 367 [M+H].sup.+
Example 171
N-[2-hydroxy-1-(2-methoxy-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzami-
de
[1415] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.39-2.44 (s, 3H), 3.53-3.68 (m, 2H), 3.84-3.87 (s, 3H), 5.43-5.51
(m, 1H), 6.91-6.98 (m, 1H), 6.99-7.03 (m, 1H), 7.22-7.29 (m, 1H),
7.33-7.38 (m, 1H), 7.63-7.69 (m, 2H), 7.84-7.92 (m, 1H), 8.05-8.12
(m, 2H), 8.70-8.87 (m, 2H)
[1416] Formula: C.sub.22H.sub.22N.sub.2O.sub.3
[1417] Calc MW: 362.43
[1418] MS (ESI) m/z: 363 [M+H].sup.+
Example 172
N-(2-hydroxy-1-naphthalen-1-yl-ethyl)-4-(3-methyl-pyridin-4-yl)-benzamide
[1419] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.38-2.43 (m, 3H), 3.81-3.91 (m, 2H), 5.90-6.02 (m, 1H), 7.49-7.69
(m, 6H), 7.83-7.91 (m, 2H), 7.95-8.01 (m, 1H), 8.06-8.14 (m, 2H),
8.26-8.34 (m, 1H), 8.70-8.85 (m, 2H);
[1420] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1421] Calc MW: 382.46
[1422] MS (ESI) m/z: 383 [M+H].sup.+
Example 173
N-(2-hydroxy-1-p-tolyl-ethyl)-4-(3-methyl-pyridin-4-yl)-benzamide
[1423] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.27-2.29 (s, 3H), 2.40-2.43 (s, 3H), 3.58-3.74 (m, 2H), 5.02-5.12
(m, 1H), 7.12-7.20 (m, 2H), 7.26-7.33 (m, 2H), 7.62-7.69 (m, 2H),
7.85-7.91 (m, 1H), 8.03-8.09 (m, 2H), 8.73-8.87 (m, 2H)
[1424] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1425] Calc MW: 346.43
[1426] MS (ESI) m/z: 347 [M+H].sup.+
Example 174
N-[1-(3-chloro-4-methoxy-phenyl)-2-hydroxy-ethyl]-4-(3-methyl-pyridin-4-yl-
)-benzamide
[1427] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.39-2.42 (s, 3H), 3.61-3.73 (m, 2H), 3.81-3.85 (m, 3H), 4.98-5.14
(m, 1H), 7.09-7.15 (m, 1H), 7.31-7.38 (m, 1H), 7.46-7.49 (m, 1H),
7.64-7.70 (m, 2H), 7.86-7.92 (m, 1H), 7.99-8.12 (m, 2H), 8.66-8.87
(m, 2H)
[1428] Formula: C.sub.22H.sub.21ClN.sub.2O.sub.3
[1429] Calc MW: 396.87
[1430] MS (ESI) m/z: 397 [M+H].sup.+
Example 175
N--[(R)-1-(2-methoxy-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1431] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.40-1.47 (m, 3H), 2.38-2.45 (s, 3H), 3.83-3.88 (s, 3H), 5.40-5.50
(m, 1H), 6.88-7.05 (m, 2H), 7.20-7.28 (m, 1H), 7.34-7.40 (m, 1H),
7.62-7.70 (m, 2H), 7.87-7.92 (m, 1H), 8.04-8.09 (m, 2H), 8.75-8.87
(m, 2H)
[1432] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1433] Calc MW: 346.43
[1434] MS (ESI) m/z: 347 [M+H].sup.+
Example 176
N--[(S)-1-(3,4-difluoro-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1435] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48-1.53 (m, 3H), 2.37-2.44 (s, 3H), 5.15-5.21 (m, 1H), 7.22-7.30
(m, 1H), 7.35-7.50 (m, 2H), 7.63-7.67 (m, 2H), 7.86-7.91 (m, 1H),
8.03-8.07 (m, 2H), 8.75-8.86 (m, 2H)
[1436] Formula: C.sub.21H.sub.18F.sub.2N.sub.2O
[1437] Calc MW: 352.38
[1438] MS (ESI) m/z: 353 [M+H].sup.+
Example 177
N--[(S)-1-(4-fluoro-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1439] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48-1.55 (m, 3H), 2.38-2.44 (s, 3H), 5.16-5.23 (m, 1H), 7.13-7.20
(m, 2H), 7.43-7.47 (m, 2H), 7.63-7.67 (m, 2H), 7.86-7.90 (m, 1H),
8.03-8.06 (m, 2H), 8.73-8.87 (m, 2H)
[1440] Formula: C.sub.21H.sub.19FN.sub.2O
[1441] Calc MW: 334.39
[1442] MS (ESI) m/z: 335 [M+H].sup.+
Example 178
N--[(R)-1-(4-methoxy-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1443] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.46-1.53 (m, 3H), 2.39-2.45 (s, 3H), 3.71-3.75 (s, 3H), 5.09-5.19
(m, 1H), 6.87-6.94 (m, 2H), 7.31-7.38 (m, 2H), 7.62-7.68 (m, 2H),
7.87-7.92 (m, 1H), 8.00-8.07 (m, 2H), 8.73-8.90 (m, 2H)
[1444] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1445] Calc MW: 346.43
[1446] MS (ESI) m/z: 347 [M+H].sup.+
Example 179
N--[(S)-1-(3-methoxy-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1447] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.47-1.53 (m, 3H), 2.40-2.44 (s, 3H), 3.74-3.76 (s, 3H), 5.10-5.24
(m, 1H), 6.79-6.85 (m, 1H), 6.95-7.03 (m, 2H), 7.24-7.31 (m, 1H),
7.61-7.68 (m, 2H), 7.82-7.92 (m, 1H), 8.01-8.08 (m, 2H), 8.73-8.88
(m, 2H)
[1448] Formula: C.sub.22H.sub.22N.sub.2O.sub.2
[1449] Calc MW: 346.43
[1450] MS (ESI) m/z: 347 [M+H].sup.+
Example 180
N--[(R)-1-(4-fluoro-phenyl)-ethyl]-4-(3-methyl-pyridin-4-yl)-benzamide
[1451] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48-1.54 (m, 3H), 2.38-2.44 (s, 3H), 5.12-5.31 (m, 1H), 7.11-7.24
(m, 2H), 7.38-7.50 (m, 2H), 7.61-7.69 (m, 2H), 7.83-7.94 (m, 1H),
7.99-8.14 (m, 2H), 8.69-8.91 (m, 2H)
[1452] Formula: C.sub.21H.sub.19FN.sub.2O
[1453] Calc MW: 334.39
[1454] MS (ESI) m/z: 335 [M+H].sup.+
Example 181
4-(3-methyl-pyridin-4-yl)-N--[(R)-1-(3-trifluoromethyl-phenyl)-ethyl]-benz-
amide
[1455] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.52-1.57 (m, 3H), 2.37-2.42 (s, 3H), 5.23-5.30 (m, 1H), 7.58-7.69
(m, 4H), 7.71-7.79 (m, 2H), 7.85-7.89 (m, 1H), 7.99-8.11 (m, 2H),
8.73-8.87 (m, 2H)
[1456] Formula: C.sub.22H.sub.19F.sub.3N.sub.2O
[1457] Calc MW: 384.40
[1458] MS (ESI) m/z: 385 [M+H].sup.+
Example 182
4-(3-methyl-pyridin-4-yl)-N--[(S)-1-(4-trifluoromethyl-phenyl)-ethyl]-benz-
amide
[1459] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.52-1.58 (m, 3H), 2.39-2.44 (s, 3H), 5.21-5.28 (m, 1H), 7.63-7.75
(m, 6H), 7.86-7.90 (m, 1H), 8.04-8.09 (m, 2H), 8.75-8.86 (m,
2H)
[1460] Formula: C.sub.22H.sub.19F.sub.3N.sub.2O
[1461] Calc MW: 384.40
[1462] MS (ESI) m/z: 385 [M+H].sup.+
Example 183
N-((1S,2S)-2-hydroxy-1,2-diphenyl-ethyl)-4-(3-methyl-pyridin-4-yl)-benzami-
de
[1463] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.34-2.38 (s, 3H), 4.93-5.00 (m, 1H), 5.16-5.23 (m, 1H), 7.20-7.36
(m, 6H), 7.46-7.51 (m, 4H), 7.54-7.58 (m, 2H), 7.75-7.81 (m, 3H),
8.69-8.81 (m, 2H)
[1464] Formula: C.sub.27H.sub.24N.sub.2O.sub.2
[1465] Calc MW: 408.50
[1466] MS (ESI) m/z: 409 [M+H].sup.+
Example 184
4-(3-methyl-pyridin-4-yl)-N--((S)-1-naphthalen-1-yl-ethyl)-benzamide
[1467] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.62-1.69 (m, 3H), 2.39-2.43 (s, 3H), 5.96-6.03 (m, 1H), 7.50-7.71
(m, 6H), 7.84-7.90 (m, 2H), 7.95-7.99 (m, 1H), 8.05-8.10 (m, 2H),
8.20-8.25 (m, 1H), 8.74-8.87 (m, 2H)
[1468] Formula: C.sub.25H.sub.22N.sub.2O
[1469] Calc MW: 366.46
[1470] MS (ESI) m/z: 367 [M+H].sup.+
Example 185
N-[1-(3,5-dichloro-phenyl)-2-hydroxy-ethyl]-4-(3-methyl-pyridin-4-yl)-benz-
amide
[1471] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.41-2.45 (m, 3H), 3.67-3.77 (m, 2H), 5.03-5.13 (m, 1H), 7.45-7.52
(m, 3H), 7.65-7.71 (m, 2H), 7.86-7.93 (m, 1H), 8.05-8.10 (m, 2H),
8.74-8.89 (m, 2H)
[1472] Formula: C.sub.21H.sub.18Cl.sub.2N.sub.2O.sub.2
[1473] Calc MW: 401.29
[1474] MS (ESI) m/z: 402 [M+H].sup.+
Example 186
4-pyridin-4-yl-N-(1,2,3,4-tetrahydro-naphthalen-1-yl)-benzamide
[1475] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.71-2.07 (m, 4H), 2.66-2.88 (m, 2H), 5.21-5.33 (m, 1H), 7.07-7.34
(m, 4H), 8.04-8.16 (m, 4H), 8.24-8.34 (m, 2H), 8.77-8.96 (m,
2H)
[1476] Formula: C.sub.22H.sub.20N.sub.2O
[1477] Calc MW: 328.41
[1478] MS (ESI) m/z: 329 [M+H].sup.+
[1479] The following compounds of Examples 187 to 190 were prepared
in an analogous method as described before:
Example 187
N-(2-hydroxy-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1480] .sup.1H NMR (300 MHz, DMSO-D.sub.6) .delta. ppm: 3.8 (m, 3H)
5.98 (m, 1H) 7.4-7.8 (m, 4H) 7.9 (m, 1H) 8.00 (m, 5H) 8.2 (m, 2H)
8.4 (m, 1H) 8.8 (m, 2H) 9.02 (d, 1H)
[1481] Formula: C.sub.24H.sub.20N.sub.2O.sub.2
[1482] Calc MW: 368.43
[1483] MS (ESI) positive ion: 369 [M+H].sup.+
Example 188
N--((S)-2-methoxy-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1484] .sup.1H NMR (300 MHz, DMSO-D.sub.6) .delta. ppm: 3.3 (s, 3H)
3.6 (m, 1H) 3.8 (m, 1H) 5.3 (m, 1H) 7.3-7.5 (m, 5H) 8.2 (m, 4H) 8.4
(m, 2H) 8.8 (d, 2H) 9.00 (d, 1H)
[1485] Formula: C.sub.21H.sub.20N.sub.2O.sub.2
[1486] Calc MW: 332.40
[1487] MS (ESI) positive ion: 333 [M+H].sup.+
Example 189
N-[1-(4-methoxy-naphthalen-1-yl)-ethyl]-4-pyridin-4-yl-benzamide
[1488] .sup.1H NMR (300 MHz, DMSO-D.sub.6) .delta. ppm: 1.6 (d, 3H)
3.9 (s, 3H) 5.8 (m, 1H), 7.0 (d, 1H) 7.5 (m, 3H) 8.0-8.3 (m, 8H)
8.8 (d, 2H), 9.0 (d, 1H)
[1489] Formula: C.sub.25H.sub.22N.sub.2O.sub.2
[1490] Calc MW: 382.46
[1491] MS (ESI) positive ion: 393 [M+H].sup.+
Example 190
4-(2-chloro-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-benzamide
[1492] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 8.91 (d,
J=8.1, 1H), 8.51 (dd, J=0.6, 5.2, 1H), 8.04 (d, J=8.6, 2H), 7.97
(d, J=8.7, 2H), 7.93 (dd, J=0.6, 1.6, 1H), 7.82 (dd, J=1.6, 5.3,
1H), 7.24 (t, J=8.1, 1H), 6.97 (dd, J=1.6, 3.9, 2H), 6.80 (ddd,
J=0.9, 2.5, 8.2, 1H), 5.16 (p, J=7.1, 1H), 3.74 (s, 3H), 1.48 (d,
J=7.1, 3H).
[1493] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1494] Calc MW: 366.85
[1495] MS m/z: 367.18 [M+H].sup.+, Rt=2.34 min.
Example 191
2-chloro-N--((R)-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1496] A 20-ml scintillation vial was charged with a solution of
2-chloro-4-(pyridin-4-yl)benzoic acid in DMA (20.0 mg, 0.085 mmol,
1.0 eq), a solution of HATU in DMA (39.06 mg, 0.103 mmol, 1.20 eq),
and triethylamine (28.83 .mu.L, 0.205 mmol, 2.40 eq). The mixture
was briefly shaken and a solution of (R)-1-phenylethanamine (14.52
mg, 0.1198 mmol, 1.40 eq) in DMA was added. The mixture was left to
shake at room temperature overnight. The mixture was then
concentrated in vacuo and dissolved in 1.4 ml of DMSO/methanol (1:1
v/v) and submitted for reverse phase purification to afford
(R)-2-chloro-N-(1-phenylethyl)-4-(pyridin-4-yl)benzamide (27.30 mg,
70.74% yield). .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta.
ppm: 1.44-1.48 (d, 3H), 5.11-5.17 (q, 1H), 7.25-7.30 (t, 1H),
7.35-7.40 (t, 2H), 7.41-7.45 (d, 2H), 7.62-7.66 (d, 1H), 7.98-8.01
(dd, 1H), 8.13-8.15 (d, 1H), 8.32-8.35 (d, 2H), 8.89-8.93 (d,
2H)
[1497] Formula: C.sub.20H.sub.17ClN.sub.2O
[1498] Calc MW: 336.82
[1499] MS (ESI) m/z: 337.0 [M+H].sup.+
[1500] The following compounds of the Examples 192 to 213 were
prepared as described for example 191.
Example 192
2-chloro-N--((R)-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1501] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.59-1.65 (d, 3H), 5.89-5.96 (q, 1H), 7.51-7.60 (m, 2H), 7.60-7.69
(m, 3H), 7.86-7.89 (d, 1H), 7.94-8.00 (t, 2H), 8.09-8.13 (s, 1H),
8.21-8.26 (d, 3H), 8.84-8.89 (d, 2H)
[1502] Formula: C.sub.24H.sub.19ClN.sub.2O
[1503] Calc MW: 386.88
[1504] MS (ESI) m/z: 385.3 [M-H].sup.-
Example 193
2-chloro-4-pyridin-4-yl-N-(1,2,3,4-tetrahydro-naphthalen-1-yl)-benzamide
[1505] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.62 (d, 3H), 5.93 (q, 1H), 7.52-7.60 (m, 2H), 7.65 (dd, 3H), 7.88
(d, 1H), 7.97 (t, 2H), 8.09-8.12 (s, 1H), 8.24 (d, 3H), 8.87 (d,
2H)
[1506] Formula: C.sub.22H.sub.19ClN.sub.2O
[1507] Calc MW: 362.86
Example 194
2-chloro-N-((1S,2R)-2-hydroxy-1,2-diphenyl-ethyl)-4-pyridin-4-yl-benzamide
[1508] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
4.79 (d, 1H), 5.19 (d, 1H), 7.05 (d, 1H), 7.24-7.38 (m, 7H), 7.43
(q, 4H), 7.87 (dd, 1H), 8.00 (d, 1H), 8.20 (d, 2H), 8.85 (d,
2H)
[1509] Formula: C.sub.26H.sub.21ClN.sub.2O.sub.2
[1510] Calc MW: 428.92
Example 195
2-chloro-4-pyridin-4-yl-N--((R)-1-p-tolyl-ethyl)-benzamide
[1511] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.43 (d, 3H), 2.27-2.31 (s, 3H), 5.09 (q, 1H), 7.17 (d, 2H), 7.30
(d, 2H), 7.58 (d, 1H), 7.91 (d, 1H), 8.05 (t, 3H), 8.79 (d, 2H)
[1512] Formula: C.sub.21H.sub.19ClN.sub.2O
[1513] Calc MW: 350.85
[1514] MS (ESI) m/z: 351.0 [M+H].sup.+
Example 196
2-chloro-4-pyridin-4-yl-N--((S)-1-p-tolyl-ethyl)-benzamide
[1515] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.44 (d, 3H), 2.27-2.32 (m, 3H), 5.10 (q, 1H), 7.17 (d, 2H), 7.30
(d, 2H), 7.62 (d, 1H), 7.98 (dd, 1H), 8.11-8.15 (m, 1H), 8.31 (d,
2H), 8.89 (d, 2H)
[1516] Formula: C.sub.21H.sub.19ClN.sub.2O
[1517] Calc MW: 350.85
[1518] MS (ESI) m/z: 351.0 [M+H].sup.+
Example 197
2-chloro-N-((1S,2R)-2-hydroxy-indan-1-yl)-4-pyridin-4-yl-benzamide
[1519] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.89 (dd, 1H), 3.13 (dd, 1H), 4.57 (ddd, 1H), 5.43 (d, 1H), 7.26
(tt, 3H), 7.34 (t, 1H), 7.78 (d, 1H), 7.98 (dd, 1H), 8.12 (d, 1H),
8.24 (d, 2H), 8.86 (d, 2H)
[1520] Formula: C.sub.21H.sub.17ClN.sub.2O.sub.2
[1521] Calc MW: 364.83
[1522] MS (ESI) m/z: 365.0 [M+H].sup.+
Example 198
2-chloro-N-((1R,2S)-2-hydroxy-indan-1-yl)-4-pyridin-4-yl-benzamide
[1523] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.88 (dd, 1H), 3.13 (dd, 1H), 4.57 (ddd, 1H), 5.42 (d, 1H), 7.26
(tt, 3H), 7.33 (t, 1H), 7.77 (d, 1H), 7.96 (dd, 1H), 8.09 (d, 1H),
8.16 (d, 2H), 8.83 (d, 2H)
[1524] Formula: C.sub.21H.sub.17ClN.sub.2O.sub.2
[1525] Calc MW: 364.83
[1526] MS (ESI) m/z: 365.0 [M+H].sup.+
Example 199
2-chloro-N-indan-1-yl-4-pyridin-4-yl-benzamide
[1527] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.88-1.99 (m, 1H), 2.46-2.52 (m, 1H), 2.82-2.91 (m, 1H), 2.94-3.02
(m, 1H), 5.51 (t, 1H), 7.26 (tt, 3H), 7.38 (t, 1H), 7.68 (d, 1H),
7.97 (dd, 1H), 8.12 (d, 1H), 8.24 (d, 2H), 8.86 (d, 2H)
[1528] Formula: C.sub.21H.sub.17ClN.sub.2O
[1529] Calc MW: 348.83
[1530] MS (ESI) m/z: 349.0 [M+H].sup.+
Example 200
N--[(S)-1-(4-bromo-phenyl)-ethyl]-2-chloro-4-pyridin-4-yl-benzamide
[1531] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.88-1.99 (m, 1H), 2.46-2.52 (m, 1H), 2.82-2.91 (m, 1H), 2.94-3.02
(m, 1H), 5.51 (t, 1H), 7.26 (tt, 3H), 7.38 (t, 1H), 7.68 (d, 1H),
7.97 (dd, 1H), 8.12 (d, 1H), 8.24 (d, 2H), 8.86 (d, 2H)
[1532] Formula: C.sub.20H.sub.16BrClN.sub.2O
[1533] Calc MW: 415.72
[1534] MS (ESI) m/z: 416.8 [M+H].sup.+
Example 201
2-Chloro-N--[(R)-1-(4-chloro-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1535] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.45 (d, 3H), 5.12 (q, 1H), 7.44 (q, 4H), 7.66 (d, 1H), 8.00 (dd,
1H), 8.14 (d, 1H), 8.34 (d, 2H), 8.92 (d, 2H)
[1536] Formula: C.sub.20H.sub.16Cl.sub.2N.sub.2O
[1537] Calc MW: 371.27
[1538] MS (ESI) m/z: 371.0 [M+H].sup.+
Example 202
2-chloro-N--[(S)-1-(4-chloro-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1539] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.45 (d, 3H), 5.12 (q, 1H), 7.44 (q, 4H), 7.64 (d, 1H), 7.99 (dd,
1H), 8.12 (d, 1H), 8.28 (d, 2H), 8.89 (d, 2H)
[1540] Formula: C.sub.20H.sub.16Cl.sub.2N.sub.2O
[1541] Calc MW: 371.27
[1542] MS (ESI) m/z: 369.0 [M-H].sup.-
Example 203
2-chloro-N--((R)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1543] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.56 (d, 3H), 5.30 (q, 1H), 7.49-7.57 (m, 2H), 7.61 (dd, 1H), 7.66
(d, 1H), 7.91 (t, 4H), 7.98 (dd, 1H) 8.11 (d, 1H) 8.22 (d, 2H) 8.86
(d, 2H)
[1544] Formula: C.sub.24H.sub.19ClN.sub.2O
[1545] Calc MW: 386.88
[1546] MS (ESI) m/z: 384.9 [M-H].sup.-
Example 204
2-chloro-N--((S)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1547] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.56 (d, 3H), 5.30 (q, 1H), 7.49-7.57 (m, 2H), 7.61 (dd, 1H), 7.67
(d, 1H), 7.91 (t, 4H), 7.98 (dd, 1H), 8.11 (d, 1H), 8.23 (d, 2H),
8.87 (d, 2H)
[1548] Formula: C.sub.24H.sub.19ClN.sub.2O
[1549] Calc MW: 386.88
[1550] MS (ESI) m/z: 387.0 [M+H].sup.+
Example 205
2-chloro-N-[2-hydroxy-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1551] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.50 (dd, 1H), 3.63 (dd, 1H), 3.84-3.86 (m, 3H), 5.43 (q, 1H), 6.95
(t, 1H), 7.02 (d, 1H), 7.28 (t, 1H), 7.37 (dd, 1H), 7.70 (d, 1H),
8.01 (dd, 1H), 8.14 (d, 1H), 8.31 (d, 2H), 8.90 (d, 2H)
[1552] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.3
[1553] Calc MW: 382.85
[1554] MS (ESI) m/z: 381.0 [M-H].sup.-
Example 206
2-chloro-N-(2-hydroxy-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1555] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.16-3.19 (s, 1H), 3.86 (dd, 1H), 5.90 (q, 1H), 7.51-7.60 (m, 2H),
7.62-7.71 (m, 3H), 7.88 (d, 1H), 7.99 (t, 2H), 8.12 (d, 1H), 8.28
(t, 3H), 8.88 (d, 2H)
[1556] Formula: C.sub.24H.sub.19ClN.sub.2O.sub.2
[1557] Calc MW: 402.88
[1558] MS (ESI) m/z: 403.0 [M+H].sup.+
Example 207
2-chloro-N-(2-hydroxy-1-p-tolyl-ethyl)-4-pyridin-4-yl-benzamide
[1559] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
2.28-2.31 (m, 3H), 3.62 (d, 2H), 5.01 (t, 1H), 7.17 (d, 2H), 7.30
(d, 2H), 7.67 (d, 1H), 7.99 (dd, 1H), 8.12 (d, 1H), 8.30 (d, 2H),
8.89 (d, 2H)
[1560] Formula: O.sub.21H.sub.19ClN.sub.2O.sub.2
[1561] Calc MW: 366.85
[1562] MS (ESI) m/z: 365.1 [M-H].sup.-
Example 208
2-chloro-N-[1-(3-chloro-4-methoxy-phenyl)-2-hydroxy-ethyl]-4-pyridin-4-yl--
benzamide
[1563] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.59-3.66 (m, 2H), 3.83-3.86 (s, 3H), 4.99 (t, 1H), 7.14 (d, 1H),
7.35 (dd, 1H), 7.47 (d, 1H), 7.67 (d, 1H), 7.99 (dd, 1H), 8.12 (d,
1H), 8.27 (d, 2H), 8.88 (d, 2H)
[1564] Formula: C.sub.21H.sub.18Cl.sub.2 N.sub.2O.sub.3
[1565] Calc MW: 417.29
[1566] MS (ESI) m/z: 415.0 [M-H].sup.-
Example 209
N-[1-(4-benzyloxy-phenyl)-2-hydroxy-ethyl]-2-chloro-4-pyridin-4-yl-benzami-
de
[1567] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
3.59-3.64 (m, 2H), 5.00 (t, 1H), 5.08-5.12 (m, 2H), 7.00 (d, 2H),
7.34 (t, 3H), 7.40 (t, 2H), 7.45 (d, 2H), 7.65 (d, 1H), 7.97 (dd,
1H), 8.09 (d, 1H), 8.20 (d, 2H), 8.85 (d, 2H)
[1568] Formula: O.sub.27H.sub.23ClN.sub.2O.sub.3
[1569] Calc MW: 458.94
[1570] MS (ESI) m/z: 457.1 [M-H].sup.-
Example 210
2-chloro-N--[(R)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1571] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.38 (d, 3H), 3.84-3.86 (s, 3H), 5.42 (q, 1H), 6.96 (t, 1H), 7.02
(d, 1H), 7.26 (t, 1H), 7.39 (dd, 1H), 7.64 (d, 1H), 7.99 (dd, 1H),
8.13 (d, 1H), 8.29 (d, 2H), 8.89 (d, 2H)
[1572] Formula: O.sub.21H.sub.19ClN.sub.2O.sub.2
[1573] Calc MW: 366.85
[1574] MS (ESI) m/z: 367.0 [M+H].sup.+
Example 211
2-chloro-N--[(S)-1-(3,4-difluoro-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1575] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.45 (d, 3H), 5.12 (q, 1H), 7.25-7.30 (m, 1H), 7.38-7.49 (m, 2H),
7.66 (d, 1H), 7.98 (dd, 1H), 8.12 (d, 1H), 8.27 (d, 2H), 8.88 (d,
2H)
[1576] Formula: C.sub.20H.sub.15ClF.sub.2N.sub.2O
[1577] Calc MW: 372.80
[1578] MS (ESI) m/z: 373.0 [M+H].sup.+
Example 212
2-chloro-N--[(R)-1-(4-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1579] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.44 (d, 3H), 3.75-3.75 (s, 3H), 5.09 (q, 1H), 6.93 (d, 2H), 7.35
(d, 2H), 7.62 (d, 1H), 7.97 (dd, 1H), 8.11 (d, 1H), 8.27 (d, 2H),
8.88 (d, 2H)
[1580] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1581] Calc MW: 366.85
[1582] MS (ESI) m/z: 365.1 [M-H].sup.-
Example 213
2-chloro-N--[(S)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1583] .sup.1H NMR (500 MHz, DMSO-D.sub.6/D.sub.2O) .delta. ppm:
1.48 (d, 3H), 3.74-3.76 (s, 3H), 5.19 (q, 1H), 7.65 (t, 3H), 7.74
(d, 2H), 7.93 (dd, 1H), 8.08 (dd, 3H), 8.81 (d, 2H).
[1584] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1585] Calc MW: 366.85
Example 214
N--[(R)-1-(3-methoxy-phenyl)-2-pyrrolidin-1-yl-ethyl]-4-pyridin-4-yl-benza-
mide
[1586] The synthesis of the title compound was performed as
described for Example 104
[1587] Formula: C.sub.25H.sub.27N.sub.3O.sub.2
[1588] Calc MW: 401.51
[1589] The following compounds of Examples 215 to 242 were prepared
as described for example 105.
Example 215
3-fluoro-N--((R)-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1590] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1591] Formula: C.sub.20H.sub.17FN.sub.2O
[1592] Calc MW: 320.37
[1593] MS (ESI) m/z: 321 [M+H].sup.+
Example 216
3-fluoro-N--((S)-1-phenyl-ethyl)-4-pyridin-4-yl-benzamide
[1594] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1595] Formula: C.sub.20H.sub.17FN.sub.2O
[1596] Calc MW: 320.37
[1597] MS (ESI) m/z: 3210 [M+H].sup.+
Example 217
3-fluoro-N--((R)-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1598] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H), 7.76-7.80 (m, 1H),
7.84-7.89 (m, 5H), 8.20-8.24 (m, 2H), 8.33-8.37 (m, 1H), 8.86-8.91
(m, 2H)
[1599] Formula: C.sub.24H.sub.19FN.sub.2O
[1600] Calc MW: 370.43
[1601] MS (ESI) m/z: 371 [M+H].sup.+
Example 218
3-fluoro-N-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-4-pyridin-4-yl-benzamide
[1602] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 5.31-5.34 (s,
1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H),
7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
[1603] Formula: C.sub.26H.sub.21FN.sub.2O.sub.2
[1604] Calc MW: 412.46
[1605] MS (ESI) m/z: 413 [M+H].sup.+
Example 219
3-fluoro-N-((1S,2R)-2-hydroxy-1,2-diphenyl-ethyl)-4-pyridin-4-yl-benzamide
[1606] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 5.31-5.34 (s,
1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H),
7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
[1607] Formula: C.sub.26H.sub.21FN.sub.2O.sub.2
[1608] Calc MW: 412.46
[1609] MS (ESI) m/z: 413 [M+H].sup.+
Example 220
3-fluoro-4-pyridin-4-yl-N--((R)-1-p-tolyl-ethyl)-benzamide
[1610] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 2.1 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89
(m, 3H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
[1611] Formula: C.sub.21H.sub.19FN.sub.2O
[1612] Calc MW: 334.39
[1613] MS (ESI) m/z: 335 [M+H].sup.+
Example 221
3-fluoro-4-pyridin-4-yl-N--((S)-1-p-tolyl-ethyl)-benzamide
[1614] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 2.1 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89
(m, 3H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
[1615] Formula: C.sub.21H.sub.19FN.sub.2O
[1616] Calc MW: 334.39
[1617] MS (ESI) m/z: 335 [M+H].sup.+
Example 222
3-fluoro-N-((1S,2R)-2-hydroxy-indan-1-yl)-4-pyridin-4-yl-benzamide
[1618] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.5 (m, 2H),
2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1619] Formula: C.sub.21H.sub.17FN.sub.2O.sub.2
[1620] Calc MW: 348.38
[1621] MS (ESI) m/z: 349 [M+H].sup.+
Example 223
3-fluoro-N-((1R,2S)-2-hydroxy-indan-1-yl)-4-pyridin-4-yl-benzamide
[1622] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.5 (m, 2H),
2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1623] Formula: C.sub.21H.sub.17FN.sub.2O.sub.2
[1624] Calc MW: 348.38
[1625] MS (ESI) m/z: 349 [M+H].sup.+
Example 224
3-fluoro-N-((1R,2R)-2-hydroxy-indan-1-yl)-4-pyridin-4-yl-benzamide
[1626] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.5 (m, 2H),
2.0 (m, 1H) 3.2 (s, 1H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1627] Formula: C.sub.21H.sub.17FN.sub.2O.sub.2
[1628] Calc MW: 348.38
[1629] MS (ESI) m/z: 349 [M+H].sup.+
Example 225
3-fluoro-N-indan-1-yl-4-pyridin-4-yl-benzamide
[1630] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 0.9 (m, 2H),
2.0 (m, 2H) 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m,
3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1631] Formula: C.sub.21H.sub.17FN.sub.2O
[1632] Calc MW: 332.38
[1633] MS (ESI) m/z: 333 [M+H].sup.+
Example 226
N--[(S)-1-(4-bromo-phenyl)-ethyl]-3-fluoro-4-pyridin-4-yl-benzamide
[1634] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1635] Formula: C.sub.20H.sub.16BrFN.sub.2O
[1636] Calc MW: 399.26
[1637] MS (ESI) m/z: 399 [M+H].sup.+
Example 227
N--[(R)-1-(4-chloro-phenyl)-ethyl]-3-fluoro-4-pyridin-4-yl-benzamide
[1638] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1
(m, 2H), 8.86-8.91 (m, 2H)
[1639] Formula: C.sub.20H.sub.16ClFN.sub.2O
[1640] Calc MW: 354.81
[1641] MS (ESI) m/z: 355 [M+H].sup.+
Example 228
N--[(S)-1-(4-chloro-phenyl)-ethyl]-3-fluoro-4-pyridin-4-yl-benzamide
[1642] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.39-7.41 (m, 4H), 7.84-7.89 (m, 3H), 8.1
(m, 2H), 8.86-8.91 (m, 2H)
[1643] Formula: C.sub.20H.sub.16ClFN.sub.2O
[1644] Calc MW: 354.81
[1645] MS (ESI) m/z: 355 [M+H].sup.+
Example 229
3-fluoro-N--((R)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1646] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.35-5.39 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 1H),
7.84-7.89 (m, 7H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1647] Formula: C.sub.24H.sub.19FN.sub.2O
[1648] Calc MW: 370.43
[1649] MS (ESI) m/z: 371 [M+H].sup.+
Example 230
3-fluoro-N--((S)-1-naphthalen-2-yl-ethyl)-4-pyridin-4-yl-benzamide
[1650] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.35-5.39 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 1H),
7.84-7.89 (m, 7H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1651] Formula: C.sub.24H.sub.19FN.sub.2O
[1652] Calc MW: 370.43
[1653] MS (ESI) m/z: 371 [M+H].sup.+
Example 231
3-fluoro-N--[(R)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1654] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 3.99-4.05 (s, 3H), 5.19-5.22 (m, 1H), 6.87-6.91 (m, 1H),
6.95-7.1 (m, 1H), 7.19-7.22 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m,
2H), 8.86-8.91 (m, 2H)
[1655] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1656] Calc MW: 350.39
[1657] MS (ESI) m/z: 351 [M+H].sup.+
Example 232
N--[(S)-1-(3,4-difluoro-phenyl)-ethyl]-3-fluoro-4-pyridin-4-yl-benzamide
[1658] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2 H)
[1659] Formula: C.sub.20H.sub.15F.sub.3N.sub.2O
[1660] Calc MW: 356.35
[1661] MS (ESI) m/z: 357 [M+H].sup.+
Example 233
3-fluoro-N--[(S)-1-(4-fluoro-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1662] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1663] Formula: C.sub.20H.sub.16F.sub.2N.sub.2O
[1664] Calc MW: 338.36
[1665] MS (ESI) m/z: 338 [M+H].sup.+
Example 234
3-fluoro-N--[(R)-1-(4-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1666] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 6.95-7.1 (m, 2H), 7.19-7.22 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1667] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1668] Calc MW: 350.39
[1669] MS (ESI) m/z: 351 [M+H].sup.+
Example 235
3-fluoro-N-[1-(4-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1670] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1671] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1672] Calc MW: 350.39
[1673] MS (ESI) m/z: 351 [M+H].sup.+
Example 236
3-fluoro-N--[(S)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1674] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 6.87-6.91 (m, 1H), 6.95-7.1 (m, 2H),
7.19-7.22 (m, 1H), 7.52-7.70 (m, 2H), 7.84-7.89 (m, 3H), 8.1 (m,
2H), 8.86-8.91 (m, 2H)
[1675] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1676] Calc MW: 350.39
[1677] MS (ESI) m/z: 351 [M+H].sup.+
Example 237
3-fluoro-N--[(R)-1-(4-fluoro-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1678] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.19-7.22 (m, 2H), 7.52-7.70 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1679] Formula: C.sub.20H.sub.16F.sub.2N.sub.2O
[1680] Calc MW: 338.36
[1681] MS (ESI) m/z: 338 [M+H].sup.+
Example 238
3-fluoro-4-pyridin-4-yl-N--[(R)-1-(3-trifluoromethyl-phenyl)-ethyl]-benzam-
ide
[1682] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1683] Formula: C.sub.21H.sub.16F.sub.4N.sub.2O
[1684] Calc MW: 388.36
[1685] MS (ESI) m/z: 389 [M+H].sup.+
Example 239
3-fluoro-4-pyridin-4-yl-N--[(S)-1-(4-trifluoromethyl-phenyl)-ethyl]-benzam-
ide
[1686] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.19-5.22 (m, 1H), 7.52-7.70 (m, 2H), 7.76-7.80 (m, 2H),
7.84-7.89 (m, 3H), 8.1 (m, 2H), 8.86-8.91 (m, 2H)
[1687] Formula: C.sub.21H.sub.16F.sub.4N.sub.2O
[1688] Calc MW: 388.36
[1689] MS (ESI) m/z: 389 [M+H].sup.+
Example 240
3-fluoro-N-((1S,2S)-2-hydroxy-1,2-diphenyl-ethyl)-4-pyridin-4-yl-benzamide
[1690] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 5.31-5.34 (s,
1H), 5.45-5.51 (m, 1H), 7.52-7.70 (m, 7H), 7.76-7.80 (m, 4H),
7.84-7.89 (m, 2H), 7.95-8.01 (m, 2H), 8.86-8.91 (m, 2H)
[1691] Formula: C.sub.26H.sub.21FN.sub.2O.sub.2
[1692] Calc MW: 412.46
[1693] MS (ESI) m/z: 412 [M+H].sup.+
Example 241
3-fluoro-N--((S)-1-naphthalen-1-yl-ethyl)-4-pyridin-4-yl-benzamide
[1694] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H), 7.76-7.80 (m, 1H),
7.84-7.89 (m, 5H), 8.20-8.24 (m, 2H), 8.33-8.37 (m, 1H), 8.86-8.91
(m, 2H)
[1695] Formula: C.sub.24H.sub.19FN.sub.2O
[1696] Calc MW: 370.43
[1697] MS (ESI) m/z: 371 [M+H].sup.+
Example 242
3-fluoro-N--[(S)-1-(2-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1698] .sup.1H NMR (500 MHz, D.sub.2O) .delta. ppm: 1.57-1.67 (m,
3H), 3.99-4.05 (s, 3H), 5.88-5.99 (m, 1H), 7.52-7.70 (m, 4H),
7.76-7.80 (m, 1H), 7.84-7.89 (m, 1H), 7.95-8.01 (m, 5H), 8.86-8.91
(m, 2H)
[1699] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1700] Calc MW: 350.39
[1701] MS (ESI) m/z: 351.1 [M+H].sup.+
[1702] The following compounds of Examples 243 to 249 were prepared
in analogous manner as described above.
Example 243
2-chloro-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1703] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 8.97 (d,
J=8.2, 1H), 8.68 (d, J=6.0, 2H), 7.96 (d, J=1.6, 1H), 7.84 (dd,
J=1.6, 7.9, 1H), 7.80-7.75 (m, 2H), 7.26 (t, J=8.1, 1H), 7.01-6.96
(m, 2H), 6.84-6.79 (m, 1H), 5.11 (p, J=7.3, 1H), 3.76 (s, 3H), 1.43
(d, J=7.0, 3H).
[1704] Formula: C.sub.21H.sub.19ClN.sub.2O.sub.2
[1705] Calc MW: 366.85
[1706] MS m/z: 366.92 [M+H].sup.+, Rt=2.11 min
Example 244
3-fluoro-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1707] .sup.1H NMR (400 MHz, DMSO-D.sub.6) .delta. ppm: 8.96 (d,
J=8.0, 1H), 8.71 (d, J=6.0, 2H), 7.89 (s, 1H), 7.88-7.85 (m, 1H),
7.77 (t, J=8.0, 1H), 7.63 (d, J=4.7, 2H), 7.25 (t, J=8.1, 1H), 6.97
(dd, J=1.9, 4.5, 2H), 6.81 (dd, J=2.5, 8.2, 1H), 5.15 (p, J=7.2,
1H), 3.75 (s, 3H), 1.49 (d, J=7.1, 3H).
[1708] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1709] Calc MW: 350.39
[1710] MS m/z: 350.95 [M+H].sup.+, Rt=2.16 min
Example 245
2-fluoro-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1711] Formula: C.sub.21H.sub.19FN.sub.2O.sub.2
[1712] Calc MW: 350.39
Example 246
4-(3-fluoro-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-2-methyl-ben-
zamide
[1713] Formula: C.sub.22H.sub.21FN.sub.2O.sub.2
[1714] Calc MW: 364.42
Example 247
4-(3-fluoro-pyridin-4-yl)-2-methoxy-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-be-
nzamide
[1715] Formula: C.sub.22H.sub.21FN.sub.2O.sub.3
[1716] Calc MW: 380.42
Example 248
4-(2-fluoro-5-methyl-pyridin-4-yl)-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-ben-
zamide
[1717] Formula: C.sub.22H.sub.21FN.sub.2O.sub.2
[1718] Calc MW: 364.42
Example 249
2-ethoxy-N--[(R)-1-(3-methoxy-phenyl)-ethyl]-4-pyridin-4-yl-benzamide
[1719] Formula: C.sub.23H.sub.24N.sub.2O.sub.3
[1720] Calc MW: 376.45
II. Biological Investigations
[1721] II.1 Activity studies:
ROCK-2 Assay
[1722] In 50 .mu.l final assay volume hROCK-2 (Upstate) (0.8 nM) is
incubated with 20 mM HEPES pH 7.5, 10 mM MgCl.sub.2, 0.01% Triton
X-100, 100 .mu.M Na.sub.3VO.sub.4, 1.5 .mu.M biotinylated S6
peptide (biotin-RRRLSSLRA-NH.sub.2, Anaspec), 1 mM DTT, 5 .mu.M
ATP, 5 .mu.Ci/ml [.sup.33P]-ATP, test compound and 1% DMSO in
96-well microplates at room temperature for 60 min. The reaction is
stopped by addition of 150 .mu.l of 0.1 M EDTA in Dulbecco's PBS.
170 .mu.l from each well are loaded onto a FlashPlate (PerkinElmer)
and incubated at room temperature for 30 min. After 3.times.
washing with 250 .mu.l PBS containing 0.05% Tween80 the FlashPlate
is sealed and read on a Microbeta (PerkinElmer) and the data is
analyzed using GraphPad Prism to determine the IC.sub.50 and K,
values.
TABLE-US-00009 Example Ki (ROCK 2) 1 ++ 2 ++ 3 + 4 ++ 5 ++ 6 ++ 7
++ 8 + 10 + 14 + 15 + 16 + 18 ++ 19 + 27 ++ 28 ++ 29 + 30 ++ 31 ++
32 ++ 33 + 34 + 35 ++ 36 ++ 39 + 40 + 41 ++ 44 + 45 ++ 46 ++ 47 ++
48 + 49 + 53 + 71 + 72 ++ 75 ++ 76 + 79 + 80 + 82 + 84 ++ 84 ++ 85
++ 86 + 87 ++ 88 ++ 89 + 90 ++ 91 ++ 94 ++ 95 + 96 ++ 97 ++ 98 ++
99 ++ 101 ++ 102 ++ 103 ++ 106 ++ 107 + 112 ++ 114 + 130 + 132 ++
135 ++ 140 ++ 149 ++ 150 ++ 151 ++ 152 ++ 153 ++ 155 ++ 156 ++ 157
++ 159 ++ 160 + 166 + 168 + 170 + 171 + 172 ++ 175 + 179 + 180 ++
181 ++ 185 + 187 ++ 188 ++ 189 + 190 ++ 191 + 192 ++ 217 ++ 229 +
236 + 243 ++ 244 ++ 245 ++ 246 ++ 247 ++ 248 ++ 249 ++ Key:
K.sub.i(ROCK 2)* + between 50 and 500 nM ++ <50 nM
II.2 In Vivo Data--Determination of Antinociceptive Effect
II.2.1 Spinal Nerve (L5L6) Ligation Model of Neuropathic Pain
[1723] As previously described in detail by Kim and Chung (Kim S.
H., Chung J. M., An experimental model for peripheral neuropathy
produced by segmental spinal nerve ligation in the rat. Pain 1992,
50, 355-363), in anesthesized rats, a 1.5 cm incision was made
dorsal to the lumbosacral plexus. The paraspinal muscles (left
side) were separated from the spinous processes, the L5 and L6
spinal nerves isolated and tightly ligated with 3-0 silk threads.
Following hemostasis, the wound was sutured and coated with
antibiotic ointment. The rats were allowed to recover and then
placed in a cage with soft bedding for 7-14 days before behavioral
testing for mechanical allodynia (Chaplan S.R., Bach, F. W., Pogrel
J. W., Chung J.M. and Yaksh T.L., Quantitative assessment of
tactile allodynia in the rat paw. Journal of Neuroscience Methods,
1994, 53(1), 55-63.
II.2.2 Sciatic Nerve Ligation Model of Neuropathic Pain
[1724] As previously described in detail by Bennett and Xie
(Bennett G. J.; Xie Y-K., A peripheral mononeuropathy in rat that
produces disorders of pain sensation like those seen in man. Pain
1988, 33, 87-107), in anesthetized rats, a 1.5 cm incision was made
0.5 cm below the pelvis and the biceps femoris and the gluteous
superficialis (right side) were separated. The sciatic nerve was
exposed, isolated, and four loose ligatures (5-0 chromic catgut)
with 1 mm spacing were placed around it. The rats were allowed to
recover and then placed in a cage with soft bedding for 14-21 days
before behavioral testing for mechanical allodynia. Selected
analogs of compounds of the invention, dosed either i.p. or p.o.
demonstrated >30% decrease in tactile allodynia in the spinal
nerve or sciatic nerve injury models of neuropathic pain at doses
ranging from 1-150 mg/kg.
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