U.S. patent application number 10/747034 was filed with the patent office on 2004-09-09 for npy y5 antagonist.
This patent application is currently assigned to Shionogi & Co., Ltd.. Invention is credited to Hanasaki, Kohji, Kawanishi, Yasuyuki, Okada, Tetsuo, Takenaka, Hideyuki.
Application Number | 20040176462 10/747034 |
Document ID | / |
Family ID | 26575482 |
Filed Date | 2004-09-09 |
United States Patent
Application |
20040176462 |
Kind Code |
A1 |
Kawanishi, Yasuyuki ; et
al. |
September 9, 2004 |
NPY Y5 antagonist
Abstract
The present invention provides a pharmaceutical composition for
use as an NPY Y5 receptor antagonist comprising a compound of the
formula (I): 1 wherein R.sup.1 is lower alkyl, cycloalkyl or the
like, R.sup.2 is hydrogen, lower alkyl or the like, n is 1 or 2, X
is lower alkylene, lower alkenylene, arylene, cycloalkylene or the
like, Y is CONR.sup.7, CSNR.sup.7, NR.sup.7CO, NR.sup.7CS or the
like, Z is lower alkyl, optionally substituted carbocyclyl,
optionally substituted heterocyclyl or the like and R.sup.7 is
hydrogen or lower alkyl, prodrug, pharmaceutically acceptable salt
or solvate thereof
Inventors: |
Kawanishi, Yasuyuki; (Osaka,
JP) ; Takenaka, Hideyuki; (Shiga, JP) ;
Hanasaki, Kohji; (Osaka, JP) ; Okada, Tetsuo;
(Osaka, JP) |
Correspondence
Address: |
BIRCH STEWART KOLASCH & BIRCH
PO BOX 747
FALLS CHURCH
VA
22040-0747
US
|
Assignee: |
Shionogi & Co., Ltd.
|
Family ID: |
26575482 |
Appl. No.: |
10/747034 |
Filed: |
December 30, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10747034 |
Dec 30, 2003 |
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10111981 |
May 1, 2002 |
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6699891 |
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10111981 |
May 1, 2002 |
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PCT/JP00/08197 |
Nov 21, 2000 |
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Current U.S.
Class: |
514/602 ;
514/603; 564/86; 564/99 |
Current CPC
Class: |
A61K 31/00 20130101;
A61K 31/18 20130101; A61K 31/4196 20130101; A61K 31/433 20130101;
C07C 2601/04 20170501; C07D 233/68 20130101; A61K 31/4453 20130101;
C07C 311/07 20130101; C07C 2601/14 20170501; A61K 31/4035 20130101;
A61K 31/505 20130101; A61P 43/00 20180101; C07D 231/12 20130101;
C07D 307/68 20130101; C07C 2602/44 20170501; C07D 215/36 20130101;
C07D 333/72 20130101; C07C 311/08 20130101; A61K 31/402 20130101;
C07C 2601/08 20170501; C07D 231/16 20130101; C07D 277/56 20130101;
C07C 311/20 20130101; C07D 219/10 20130101; A61K 31/41 20130101;
C07D 207/16 20130101; A61P 3/00 20180101; C07C 311/46 20130101;
C07D 209/88 20130101; C07D 249/08 20130101; C07D 211/62 20130101;
C07C 323/40 20130101; A61K 31/63 20130101; C07D 209/08 20130101;
C07D 307/91 20130101; C07D 215/38 20130101; A61K 31/351 20130101;
A61P 3/04 20180101; C07C 2601/02 20170501; C07D 285/06 20130101;
A61K 31/42 20130101; A61K 31/4965 20130101; A61K 31/44 20130101;
C07C 311/06 20130101; A61K 31/425 20130101; C07D 317/66 20130101;
C07C 2602/08 20170501; C07C 2602/10 20170501; C07D 231/56 20130101;
A61K 31/357 20130101; A61K 31/428 20130101; A61K 31/495 20130101;
C07C 311/21 20130101; A61K 31/341 20130101; A61K 31/635 20130101;
C07D 211/58 20130101; A61K 31/451 20130101; C07C 311/14 20130101;
C07D 207/12 20130101; C07D 277/70 20130101; A61K 31/423 20130101;
C07C 2603/18 20170501; C07D 217/04 20130101; C07D 311/16 20130101;
C07D 213/75 20130101; A61K 31/4015 20130101; C07D 209/48 20130101;
C07D 239/42 20130101; A61K 31/37 20130101; C07D 207/09 20130101;
C07D 233/56 20130101; A61K 31/381 20130101; C07D 213/82 20130101;
A61K 31/421 20130101; A61K 31/5375 20130101; C07D 295/135 20130101;
C07D 333/38 20130101; A61K 31/4409 20130101 |
Class at
Publication: |
514/602 ;
514/603; 564/099; 564/086 |
International
Class: |
A61K 031/18 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 26, 1999 |
JP |
11-336469 |
Dec 14, 1999 |
JP |
11-353786 |
Claims
1. A pharmaceutical composition comprising a compound of the
formula (I): 244wherein R.sup.1 is optionally substituted lower
alkyl, optionally substituted cycloalkyl or optionally substituted
aryl, R.sup.2 is hydrogen or lower alkyl, and R.sup.1 and R.sup.2
taken together may form lower alkylene, n is 1 or 2, R.sup.3,
R.sup.4, R.sup.5 and R.sup.6 are each independently hydrogen or
lower alkyl, 245is optionally substituted cycloalkylene or
optionally substituted bicycloalkylene, and p and q are each
independently 0 or 1, R.sup.7 is hydrogen or lower alkyl, and Z is
optionally substituted aryl, prodrug, pharmaceutically acceptable
salt or hydrate thereof.
2. The pharmaceutical composition claimed in claim 1 wherein
R.sup.2 is hydrogen or lower alkyl.
3. The pharmaceutical composition claimed in claim 1 wherein
R.sup.1 is optionally substituted lower alkyl or optionally
substituted cycloalkyl, and p and q are 0.
4. The pharmaceutical composition claimed in any one of claims 1 to
3 wherein R.sup.1 is optionally substituted C3 to C10 alkyl.
5. The pharmaceutical composition claimed in any one of claims 1 to
3 which is an anti-obestic agent.
6. The pharmaceutical composition claimed in any one of claims 1 to
3 which is an anorectic agent.
7. A method for treating obesity comprising administering to a
subject that is obese an effective dose of a compound claimed in
any one of claims 1 to 3.
8. A method for suppressing food intake comprising administering to
a subject that is obese an effective dose of a compound claimed in
any one of claims 1 to 3.
9. A compound of the formula (I): 246wherein the symbols are the
same as defined in claim 1, prodrug, pharmaceutically acceptable
salt or hydrate thereof.
10. The compound described in claim 9 wherein R.sup.1 is optionally
substituted C3 to C10 alkyl or optionally substituted C5 to C6
cycloalkyl, prodrug, pharmaceutically acceptable salt or hydrate
thereof.
11. The compound described in claim 9 wherein 247is optionally
substituted cyclohexylene and p and q are simultaneously 0,
prodrug, pharmaceutically acceptable salt or hydrate thereof.
12. The compound described in claim 9 or 10 wherein Y is CONH,
prodrug, pharmaceutically acceptable salt or hydrate thereof.
13. A pharmaceutical composition comprising the compound claims in
claim 9 or 10, prodrug, pharmaceutically acceptable salt or hydrate
thereof and a pharmaceutically acceptable carrier.
Description
TECHNICAL FIELD
[0001] The present invention relates to a pharmaceutical
composition for use as an NPY Y5 receptor antagonist, specifically,
anti-obestic agent and novel compounds having an anti-obestic
activity.
BACKGROUND ART
[0002] Neuropeptide Y (hereinafter referred to as NPY) is a peptide
which consists of 36 amino acid residues and was isolated from
porcine brain in 1982. NPY is widely distributed in the central
nervous system and peripheral tissues of humans and animals.
[0003] It has been reported that NPY possesses a stimulating
activity of food intake, an anti-seizure activity, a
learning-promoting activity, an anti-anxiety activity, an
anti-stress activity etc. in central nervous system, and it may be
pivotally involved in the central nervous system diseases such as
depression, Alzheimer's disease and Parkinson's disease. NPY is
thought to be associated with the cardiovascular diseases, since it
induces a contraction of smooth muscles such as blood vessels or
cardiac muscles in the peripheral tissues. Furthermore, NPY is also
known to be involved in the metabolic diseases such as obesity,
diabetes, and hormone abnormalities (Trends in Pharmacological
Sciences, Vol.15, and 153 (1994)). Therefore, an NPY receptor
antagonist is expected as a medicine for preventing or treating
various diseases involved in the NPY receptor.
[0004] Subtypes of Y1, Y2, Y3, Y4, Y5, and Y6 have now been
identified as the NPY receptor (Trends in Pharmacological Sciences,
Vol.18, and 372 (1997)). It has been suggested that the Y5 receptor
is at least involved in the feeding behavior and its antagonist is
expected as an anti-obestic agent (Peptides, Vol.18, and 445
(1997)).
[0005] Quinazoline compounds having similar structures to those of
the compounds of the present invention and exhibiting an NPY
receptor antagonistic activity are described in WO97/20820,
WO97/20821, WO97/20823 and the like. In addition, it is described
that urea derivatives having a sulfonamide group and amide
derivatives having a sulfonyl group in WO 99/64349 and benzyl
sulfonamide derivatives in EP1010691-A, have an NPY antagonistic
activity.
[0006] Compounds having similar structures to those of the
compounds of the present invention are described in JP59-16871-A
and WO97/15567. Their activities are quite different from that of
the present invention and these documents do not suggest the
present invention.
DISCLOSURE OF INVENTION
[0007] The object of the present invention is to provide a superior
pharmaceutical composition for use as an NPY Y5 receptor antagonist
and novel compounds having the activity.
[0008] The present invention provides
[0009] [1] A pharmaceutical composition for use as an NPY Y5
receptor antagonist comprising a compound of the formula (I): 2
[0010] wherein R.sup.1 is optionally substituted lower alkyl,
optionally substituted cycloalkyl or optionally substituted
aryl,
[0011] R.sup.2 is hydrogen or lower alkyl, and R.sup.1 and R.sup.2
taken together may form lower alkylene,
[0012] n is 1 or 2,
[0013] X is optionally substituted lower alkylene,
[0014] optionally substituted lower alkenylene,
[0015] optionally substituted --CO-lower alkylene,
[0016] optionally substituted --CO-lower alkenylene or 3
[0017] wherein R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each
independently hydrogen or lower alkyl, 4
[0018] is optionally substituted cycloalkylene, optionally
substituted cycloalkenylene, optionally substituted
bicycloalkylene, optionally substituted arylene or optionally
substituted heterocyclediyl and p and q are each independently 0 or
1,
[0019] --NR.sup.2--X-- may be 5
[0020] wherein 6
[0021] is piperidinediyl, piperazinedlyl, pyridinediyl,
pyrazinediyl, pyrrolidinediyl or pyrrolediyl and U is single bond,
lower alkylene or lower alkenylene,
[0022] Y is OCONR.sup.7, CONR.sup.7, CSNR.sup.7, NR.sup.7CO or
NR.sup.7CS,
[0023] R.sup.7 is hydrogen or lower alkyl, and
[0024] Z is optionally substituted lower alkyl, optionally
substituted lower alkenyl, optionally substituted amino, optionally
substituted lower alkoxy, optionally substituted carbocyclyle or
optionally substituted heterocyclyl,
[0025] prodrug, pharmaceutically acceptable salt or solvate
thereof,
[0026] [2] The pharmaceutical composition for use as an NPY Y5
receptor antagonist described in [1] wherein R.sup.2 is hydrogen or
lower alkyl and Z is optionally substituted lower alkyl, optionally
substituted lower alkenyl, optionally substituted lower alkoxy,
optionally substituted carbocyclyl, optionally substituted
heterocyclyl or optionally substituted amino, provided that R.sup.1
is optionally substituted C3 to C10 alkyl when Z is optionally
substituted amino,
[0027] [3] The pharmaceutical composition for use as an NPY Y5
receptor antagonist described in [1] wherein R.sup.1 is optionally
substituted lower alkyl or optionally substituted cycloalkyl, X is
optionally substituted lower alkylene, optionally substituted lower
alkenylene or 7
[0028] wherein 8
[0029] is the same as defined in [1], and
[0030] Z is optionally substituted lower alkyl, optionally
substituted carbocyclyl or optionally substituted heterocyclyl,
[0031] [4] The pharmaceutical composition for use as an NPY Y5
receptor antagonist described in any one of [1] to [3] wherein
R.sup.1 is optionally substituted C3 to C10 alkyl,
[0032] [5] The pharmaceutical composition for use as an NPY Y5
receptor antagonist described in any one of [1] to [4] which is an
anti-obestic agent,
[0033] [6] The pharmaceutical composition for use as an NPY Y5
receptor antagonist described in any one of [1] to [4] which is an
anorectic agent,
[0034] [7] A method for treating and/or preventing obesity
comprising administering an effective dose of an NPY Y5 receptor
antagonist described in any one of [1] to [4],
[0035] [8] A method for suppressing food intake comprising
administering an effective dose of an NPY Y5 receptor antagonist
described in any one of [1] to [4],
[0036] [9] Use of an NPY Y5 receptor antagonist described in any
one of [1] to [4] for manufacturing a medicine for treating and/or
preventing obesity,
[0037] [10] Use of an NPY Y5 receptor antagonist described in any
one of [1] to [4] for manufacturing a medicine for suppressing food
intake,
[0038] [11] A compound of the formula (I): 9
[0039] wherein X is C2 to C6 alkylene or C3 to C6 alkenylene,
R.sup.1 is optionally substituted C3 to C10 alkyl or optionally
substituted C5 to C6 cycloalkyl and the other symbols are the same
as defined in [1], provided that Z is not lower
alkylphenylamino,
[0040] hydroxy(lower)alkylphenylamino and acylphenylamino when Y is
NR.sup.7CO,
[0041] prodrug, pharmaceutically acceptable salt or solvate
thereof,
[0042] [12] The compound described in [11] wherein Z is optionally
substituted lower alkyl or optionally substituted phenyl, prodrug,
pharmaceutically acceptable salt or solvate thereof,
[0043] [13] A compound of the formula (I): 10
[0044] wherein X is 11 12
[0045] is optionally substituted cycloalkylene, optionally
substituted cycloalkenylene, optionally substituted bicycloalkylene
or optionally substituted piperidinylene, R.sup.1 is optionally
substituted C3 to C10 alkyl or optionally substituted C5 to C6
cycloalkyl and the other symbols are the same as defined in
[1],
[0046] prodrug, pharmaceutically acceptable salt or solvate
thereor,
[0047] [14] The compound described in [13] wherein is optionally
substituted cyclohexylene or optionally substituted piperidinylene
and p and q are simultaneously 0, prodrug, pharmaceutically
acceptable salt or solvate thereof,
[0048] [15] The compound described in [13] or [14] wherein Y is
CONH, prodrug, pharmaceutically acceptable salt or solvate
thereof,
[0049] [16] The compound described in any one of [13] to [15]
wherein Z is optionally substituted lower alkyl, optionally
substituted phenyl, optionally substituted pyridyl or optionally
substituted benzopyranyl, prodrug, pharmaceutically acceptable salt
or solvate thereof,
[0050] [17] A compound of the formula (I): 13
[0051] wherein X is 14
[0052] R.sup.1 is optionally substituted C3 to C10 alkyl or
optionally substituted C5 to C6 cycloalkyl,
[0053] Z is p-(lower)alkylphenyl and the other symbols are the same
as defined in [1], provided that Z is not p-n-butylphenyl when
R.sup.1 is isopropyl,
[0054] prodrug, pharmaceutically acceptable salt or solvate
thereof,
[0055] [18] A compound of the formula (I): 15
[0056] wherein X is 16 17
[0057] is heteroarylene, R.sup.1 is optionally substituted C3 to
C10 alkyl or optionally substituted C5 to C6 cycloalkyl and the
other symbols are the same as defined in [1],
[0058] prodrug, pharmaceutically acceptable salt or solvate
thereof,
[0059] [19] The compound described in [18] wherein 18
[0060] is thiophenediyl or furandiyl, prodrug, pharmaceutically
acceptable salt or solvate thereof and
[0061] [20] A pharmaceutical composition comprising the compound
described in any one of [11] to [19], prodrug, pharmaceutically
acceptable salt or solvate thereof.
BEST MODE FOR CARRYING OUT THE INVENTION
[0062] In the present specification, the term "halogen" includes
fluorine, chlorine, bromine and iodine. Fluorine or chlorine is
preferable.
[0063] The term "protective group" in "optionally protected
hydroxy" and "optionally protected hydroxy(lower)alkyl" includes
all of hydroxy protecting groups usually used. For example, acyl
such as acetyl, trichloroacetyl and benzoyl, lower alkoxycarbonyl
such as t-butoxycarbonyl, lower alkylsulfonyl such as methane
sulfonyl, lower alkoxy(lower)alkyl such as methoxymethyl,
trialkylsilyl such as t-butyldimethylsilyl are included.
[0064] The term "lower alkyl" includes C1 to C10 straight or
branched alkyl. The examples of "lower alkyl" are methyl, ethyl,
n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,
n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, n-heptyl,
isoheptyl, n-octyl, isooctyl, n-nonyl and n-decyl.
[0065] "Lower alkyl" represented by R.sup.1 is preferably C3 to C10
alkyl, more preferably C3 to C6 alkyl and most preferably isopropyl
or t-butyl.
[0066] "Lower alkyl" in other cases is preferably C1 to C6 alkyl
and more preferably C1 to C4 alkyl.
[0067] The examples of substituents of "optionally substituted
lower alkyl" represented by Z are, (1) halogen; (2) cyano;
[0068] (3) the following groups (i) to (xvi), which are optionally
substituted with one or more substituents selected from "a
substituents group .beta." defined below,
[0069] (i) hydroxy, (ii) lower alkoxy, (iii) mercapto, (iv) lower
alkylthio, (v) acyl, (vi) acyloxy, (vii) carboxy, (viii) lower
alkoxycarbonyl, (ix) imino, (x) carbamoyl, (xi) thiocarbamoyl,
(xii) lower alkylcarbamoyl, (xiii) lower alkylthiocarbamoyl, (xiv)
amino, (xv) lower alkylamino or (xvi) heterocyclylcarbonyl;
[0070] or
[0071] (4) a group of the formula: 19
[0072] wherein R.sup.10 and R.sup.11 are each independently
hydrogen or lower alkyl and when this group has two or more of
R.sup.10 and/or two or more of R.sup.11, each R.sup.10 and/or each
R.sup.11 may be different,
[0073] W is single bond, O, S or NR.sup.12,
[0074] R.sup.12 is hydrogen, lower alkyl or phenyl, 20
[0075] is cycloalkyl, bicycloalkyl, cycloalkenyl, aryl or
heterocyclyl, each of which is optionally substituted with one or
more of substituents selected from "a substituents group .alpha."
defined below and
[0076] s is an integer of 0 to 4.
[0077] In the present specification, "a substituents group .alpha."
is a group constituting of (1) halogen; (2) oxo; (3) cyano; (4)
nitro; (5) imino optionally substituted with lower alkyl or
hydroxy;
[0078] (6) the following groups (i) to (xxi), which are optionally
substituted with one or more of groups selected from the
substituents group .beta.,
[0079] (i) hydroxy, (ii) lower alky, (iii) lower alkenyl, (iv)
lower alkoxy, (v) carboxy, (vi) lower alkoxycarbonyl, (vii) acyl,
(viii) acyloxy, (ix) imino, (x) mercapto, (xi) lower alkylthio,
(xii) carbamoyl, (xiii) lower alkylcarbamoyl, (xiv)
cycloalkylcarbamoyl, (xv) thiocarbamoyl, (xvi) lower
alkylthiocarbamoyl, (xvii) lower alkylsulfinyl, (xviii) lower
alkylsulfonyl, (xix) sulfamoyl, (xx) lower alkylsulfamoyl and (xxi)
cycloalkylsulfamoyl;
[0080] (7) the following groups (i) to (v), which are optionally
substituted with the substituents group .beta., lower alkyl, lower
alkoxy(lower)alkyl, optionally protected hydroxy(lower)alkyl,
halogeno(lower)alkyl, lower alkylsulfonyl and/or arylsulfonyl,
[0081] (i) cycloalkyl, (ii) cycloalkenyl, (iii)cycloalkyloxy, (iv)
amino and (v) alkylenedioxy;
[0082] and
[0083] (8) the following groups (i) to (xii), which are optionally
substituted with the substituents group .beta., lower alkyl,
halogeno(lower)alkyl and/or oxo,
[0084] (i) phenyl, (ii) naphthyl, (iii) phenoxy, (iv)
phenyl(lower)alkoxy, (v) phenylthio, (vi) phenyl(lower)alkylthio,
(vii) phenylazo, (viii) heterocyclyl, (ix) heterocyclyloxy, (x)
heterocyclylthio, (xi) heterocyclylcarbonyl and (xii)
heterocyclylsulfonyl.
[0085] The preferable examples of the substituents group .alpha. as
substituents for B ring are halogen; nitro; hydroxy;
[0086] optionally substituted lower alkyl wherein the substituents
is halogen, cyano, phenyl, carboxy and/or lower alkoxycarbonyl;
[0087] lower alkenyl; lower alkoxycarbonyl(lower)alkenyl;
[0088] optionally substituted lower alkoxy wherein the substituents
is halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl,
lower alkylamino and/or cyano;
[0089] acyl; hydroxyimino; lower alkylthio; lower alkylsulfinyl;
sulfamoyl;
[0090] optionally substituted amino wherein the substituents is
lower alkyl optionally protected hydroxy(lower)alkyl, phenyl and/or
acyl;
[0091] alkylenedioxy; cyanophenyl; heterocyclylphenyl; biphenylyl;
phenoxy; phenylazo optionally substituted with lower alkyl; or
[0092] optionally substituted heterocyclyl wherein the substituents
is optionally protected hydroxy, mercapto, halogen, lower alkyl,
cycloalkyl, lower alkoxycarbonyl, amino, lower alkoxycarbonyl
amino, carbonyl, oxo, phenyl lower alkoxyphenyl or
heterocyclyl.
[0093] More preferable examples are halogen; lower alkyl optionally
substituted with halogen;
[0094] or lower alkoxy optionally substituted with halogen.
[0095] "A substituents group .beta." is a group consisting of
halogen, optionally protected hydroxy, mercapto, lower alkoxy,
lower alkenyl, amino, lower alkylamino, lower alkoxycarbonylamino,
lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, carbamoyl,
cyano, cycloalkyl, phenyl, phenoxy, lower alkylphenyl, lower
alkoxyphenyl, halogenophenyl, naphthyl and heterocyclyl.
[0096] Examples of the substituents for "optionally substituted
lower alkyl" represented by any other than Z (e.g., R.sup.1) are
one or more substituents selected from the substituents group
.beta.. The lower alkyl may be substituted with these substituents
at any possible positions.
[0097] The lower alkyl part in "lower alkoxy", "lower
alkoxycarbonyl", "lower alkoxycarbonyl(lower)alkyl", "lower
alkylphenyl", "lower alkoxyphenyl", "lower alkylcarbamoyl", "lower
alkylthiocarbamoyl", "lower alkylamino", "halogeno(lower)alkyl",
"hydroxy(lower)alkyl", "phenyl(lower)alkoxy", "lower alkylthio",
"phenyl(lower)alkylthio", "lower alkoxycarbonylamino", "lower
alkoxycarbonyl(lower)alkenyl", "lower alkylsulfinyl", "lower alkyl
sulfonyl", "aryl(lower)alkoxycarbonyl", "lower alkylbenzoyl" and
"lower alkoxybenzoyl" is the same as defined in the above "lower
alkyl".
[0098] Examples of substituents for "optionally substituted lower
alkoxy" are one or more substituents selected from the substituents
group .beta.. Preferable examples are phenyl, lower alkylphenyl,
lower alkoxyphenyl, naphthyl and heterocyclyl.
[0099] The term "cycloalkyl" includes C3 to C8 cyclic alkyl and
preferably C5 to C6 cyclic alkyl. Examples are cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and
cyclooctyl.
[0100] Examples of substituents for "optionally substituted
cycloalkyl" are one or more substituents selected from the
substituents group a and the cycloalkyl may be substituted with
these substituents at any possible positions.
[0101] The term "bicycloalkyl" includes a group which is formed by
excluding one hydrogen from a C5 to C8 aliphatic cycle containing
two rings which possess two or more of atoms in common. Examples
are bicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl
and bicyclo[3.2.1]octyl.
[0102] The term "lower alkenyl" includes C2 to C10, preferably C2
to C8 and more preferably C3 to C6 straight or branched alkenyl
having one or more double bonds at any possible positions. Examples
are vinyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl,
butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl,
isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl and decenyl.
[0103] The "lower alkenyl" part in "lower
alkoxycarbonyl(lower)alkenyl" is the same as the above "lower
alkenyl".
[0104] Examples of the substituents for "optionally substituted
lower alkenyl" are halogen, lower alkoxy, lower alkenyl, amino,
lower alkylamino, lower alkoxycarbonylamino, lower alkylthio, acyl,
carboxy, lower alkoxycarbonyl, carbamoyl, cyano, cycloalkyl,
phenyl, lower alkylphenyl, lower alkoxyphenyl, naphthyl and/or
heterocyclyl.
[0105] The term "acyl" includes (1) C1 to C10, preferably C1 to C6
and more preferably C1 to C4 straight or branched alkylcarbonyl or
alkenylcarbonyl, (2) C4 to C9 and preferably C4 to C7
cycloalkylcarbonyl and (3) C7 to C11 arylcarbonyl. Examples are
formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, pivaloyl,
hexanoyl, acryloyl, propioloyl, methacryloyl, crotonoyl,
cyclopropylcarbonyl, cyclohexylcarbonyl, cyclooctylcarbonyl and
benzoyl.
[0106] The "acyl" part in "acyloxy" is the same as the above.
[0107] The term "cycloalkenyl" includes a group having at least one
double bond at any possible positions in the above cycloalkyl.
Examples are cyclopropenyl, cyclobutenyl, cyclopentenyl,
cyclohexenyl and cyclohexadienyl.
[0108] Examples of substituents for "optionally substituted
cycloalkenyl" are one or more substituents selected from the
substituents group .beta..
[0109] Examples of substituents for "optionally substituted amino"
are the substituents group .beta., optionally substituted benzoyl
and/or optionally substituted heterocyclylcarbonyl wherein the
substituents is hydroxy, lower alkyl, lower alkoxy and/or lower
alkylthio.
[0110] The term "aryl" includes a monocyclic of polycyclic aromatic
carbocyclyl group and examples are phenyl, naphthyl, anthryl and
phenanthryl. "Aryl" includes aryl fused with other a non-aromatic
carbocyclyl group, for example, indanyl, indenyl, biphenylyl,
acenaphthyl, tetrahyclronaphthyl and fluorenyl. Phenyl is
preferable.
[0111] The aryl part in "aryl lower alkoxycarbonyl" is the same as
the above.
[0112] The term "optionally substituted aryl" and "optionally
substituted phenyl" represented by Z include the above "aryl" and
"phenyl" respectively, which may be substituted with the
substituents group a or lower alkyl which may be substituted with
one or more group selected from the substituents group .alpha..
[0113] Examples of the substituents for "optionally substituted
aryl" and "optionally substituted phenyl" represented by any other
than Z are one or more groups selected from the substituents group
.beta..
[0114] The term "carbocyclyl" includes the above "cycloalkyl",
"cycloalkenyl", "bicycloalkyl" and "aryl".
[0115] The term "non-aromatic carbocyclyl" includes the above
"cycloalkyl", "cycloalkenyl" and "bicycloalkyl".
[0116] The term "optionally substituted carbocyclyl" includes the
above "optionally substituted cycloalkyl", "optionally substituted
cycloalkenyl", "optionally substituted bicycloalkyl" and
"optionally substituted aryl".
[0117] The term "heterocyclyl" includes a heterocyclic group
containing at least one heteroatom arbitrarily selected from O, S
and N. For example, 5- or 6-membered heteroaryl such as pyrrolyl,
imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, oxazolyl,
oxadiazolyl, isoth, olyl, thiazolyl, thiadiazolyl, furyl and
thienyl; fused heterocyclyl consisting of two rings such as
indolyl, isoindolyl, indazolyl, indolizinyl, inclolinyl,
isoindolinyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl,
quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl,
benzopyranyl, benzimidazolyl, beinzisoxazolyl, benzoxazolyl
benbzoxadiazolyl, benzisothiazolyl, benzothiazolyl,
benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl,
benzotriazolyl, imidazopyridyl, triazoropyridyl, imidazothiazolyl,
pyrazinopyridazinyl, quinazolinyl, quinolyl, isoquinolyl,
naphthyridinyl, dihydropyridyl, tetrahydroquinolyl and
tetrahydrobenzothienyl; fused heterocyclyl consisting of three
rings such as carbazolyl, acridinyl, xanthenyl, phenothiazinyl,
phenoxathiinyl, phenoxazinyl and dibenzofuryl; and non-aromatic
heterocyclyl such as dioxanyl, thiiranyl, oxiranyl, oxathiolanyl,
azetidinyl, thianyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl,
imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl,
morpholinyl, morpholino, thiomorpholinyl, thiomorpholino,
dihydropyridyl, tetrahydrofuryl, tetrahydropyranyl,
tetrahydrothiazolyl and tetrahydroisothiazolyl.
[0118] "Fused heterocyclyl" fused with a ring other than a
heterocycle (e.g., benzothiazolyl), may connect at any possible
position.
[0119] Substituents for "optionally substituted heterocyclyl" are
the same as those for the above "optionally substituted aryl".
[0120] Heterocyclyl parts in "heterocyclylcarbonyl",
"heterocyclyloxy", "heterocyclylthio" and "heterocyclyl substituted
phenyl" are the same as the above "heterocyclyl".
[0121] The term "lower alkylene" includes a bivalent group
comprising 1 to 6 of methylene, preferably 2 to 6 of methylene and
more preferably 3 to 6 of methylene. For example, methylene,
ethylene, trimethylene, tetramethylene, pentamethylene and
hexamethylene are included. Tetramethylene is preferable.
[0122] "R.sup.1 and R.sup.2 taken together may form lower alkylene"
includes the case 21
[0123] Preferable examples are 22
[0124] Lower alkylene part in "lower alkylenedioxy" is the same as
the above "lower alkylene". Methylenedioxy or ethylenedioxy is
preferable.
[0125] The term "lower alkenylene" includes a bivalent group
comprising 2 to 6 of methylene, preferably 3 to 6 of methylene and
more preferably 4 to 5 of methylene and including at least one
double bond.
[0126] The term "cycloalkylene" includes a bivalent group which is
formed by excluding one hydrogen from the above "cycloalkyl". A
preferable example of cycloalkylene represented by X is
1,4-cyclohexanediyl.
[0127] The term "cycloalkenylene" includes a group containing at
least one double bonds in the above cycloalkylene.
[0128] The term "bicycloalkylene" includes a group which is formed
by excluding one hydrogen from the above "bicycloalkyl". Examples
are bicyclo[2.1.0]pentylene, bicyclo[2.2.1]heptylene,
bicyclo[2.2.2]octylene, and bicyclo[3.2.1]octylene.
[0129] The term "heterocyclediyl" includes a bivalent group which
is formed by excluding one hydrogen from the above "heterocyclyl".
Piperidinediyl, piperazinediyl, pyridinediyl, pyrimidinediyl,
pyrazinediyl, pyrrolidinediyl or pyrrolediyl is preferable and
piperidindiyl is more preferable.
[0130] The term "arylene" includes a bivalent group which is formed
by excluding one hydrogen from the above "aryl". Phenylene is
preferable.
[0131] The term "heteroarylene" includes aromatic groups in the
above "heterocyclediyl". Examples are pyrrolediyl, imidazolediyl,
pyrazolediyl, pyridinediyl, pyridazinediyl, pyrimidinediyl,
pyrazinediyl, triazolediyl, triazinediyl, isoxazolediyl,
oxazolediyl, oxadiazolediyl, isothiazolediyl, thiazolediyl,
thiadiazolediyl, furandiyl and thiophenediyl.
[0132] One or more groups selected from the substituents group
.beta. are examples of substituents for "optionally substituted
lower alkylene", "optionally substituted lower alkenylene",
"optionally substituted cycloalkylene", "optionally substituted
cyclohexylene", "optionally substituted bicycloalkylene",
"optionally substituted cycloalkenylene", "optionally substituted
phenylene", "optionally substituted heterocyclediyl" and
"optionally substituted piperidinylene". Halogen, hydroxy, lower
alkyl, halogeno(lower)alkyl, lower alkoxy, amino, lower alkylamino,
acyl, carboxy or lower alkoxycarbonyl is preferable. These
substituents may attach to any possible positions.
[0133] When --NR.sup.2--X-- is 23
[0134] U is preferably single bond or methylene. More preferably,
24
[0135] is 25
[0136] The compounds of the present invention include any formable
and pharmaceutically acceptable salts thereof. Examples of "the
pharmaceutically acceptable salt" are salts with mineral acids such
as hydrochloric acid, sulfuric acid, nitric acid and phosphoric
acid; salts with organic acids such as para-toluenesulfonic acid,
methanesulfonic acid, oxalic acid and citric acid; salts with
organic bases such as ammonium, trimethylammonium and
trimethylammonium; salts with alkaline metals such as sodium and
potassium; and salts with alkaline earth metals such as calcium and
magnesium.
[0137] The compounds of the present invention include solvates
thereof. Hydrate is preferable and arbitrary numbers of water
molecules may coordinate to the compound of the present
invention.
[0138] The compounds of the present invention include prodrugs
thereof. Prodrug includes derivatives of the compounds of the
present invention which have a chemically or metabolically
decomposable group and can be converted into pharmaceutically
active compounds of the present invention in vivo by solvolysis or
under the physiological conditions. The methods for selecting and
producing suitable prodrugs are described in Design of Prodrugs,
Elsevier, Amsterdam 1985.
[0139] When a compound (I) of the present invention has carboxy,
examples of prodrugs are an ester derivative and an amide
derivative, which can be produced by reacting a compound (I) having
carboxy with a suitable alcohol or a suitable amine,
respectively.
[0140] When a compound (I) of the present invention has hydroxy, an
example of prodrug,s is an acyloxy derivative, which can be
synthesized by reacting a compound (I) having hydroxy with a
suitable acyl halide or a suitable acid anhydride.
[0141] When a compound (I) of the present invention has amino, an
example of prodrugs is an amide derivative, which can be
synthesized by reacting a compound (I) having amino with a suitable
acid halide or a suitable mixed acid anhydride.
[0142] When the compound (I) of the present invention has an
asymmetric carbon atom, it includes racemates, all of enantiomers
and all of stereoisomers such as diastereomer, epimer and
enantiomer thereof.
[0143] When the compound (I) of the present invention having one or
more double bonds forms an E isomer or Z isomer, the compound (I)
includes both isomers. When X is cycloalkylene, the compound (I)
includes both of cis isomer and trans isomer.
[0144] For example, the compound (I) of the present invention can
be synthesized by the following methods.
[0145] (Compounds wherein Y.dbd.CONR.sup.7) 26
[0146] wherein Hal is halogen, Q is an amino protecting group and
the other symbols are the same as the above.
[0147] Step A
[0148] Compound 1 is reacted with Amino Compound 2 having the
desired substituent Z and R.sup.7 in a suitable solvent at
0.degree. C. to 50.degree. C. for several minutes to several hours.
As solvents, tetrahydrofuran, dimethylformamide, diethyl ether,
dichloromethane, toluene, benzene, xylene, cyclohexane, hexane,
chloroform, ethyl acetate, butyl acetate, pentane, heptane,
dioxane, acetone, acetonitrile, water, a mixture thereof etc. can
be used. An activator such as thionyl chloride, acid halide, acid
anhydride and activated ester can be used, if necessary.
[0149] Step B
[0150] Compound 3 is deprotected by the usual method and reacted
with Sulfonyl Halide 4 having the desired substituent R.sup.1 in a
suitable solvent at 0.degree. C. to 50.degree. C. for several
minutes to several hours to give Compound (I-A) wherein n is 2.
Tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane,
toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl
acetate, butyl acetate, pentane, heptane, dioxane, acetone,
acetonitrile, water and the mixture thereof etc. can be used as a
solvent.
[0151] Step C
[0152] Compound (I-B) wherein n is 1 can be synthesized by reacting
Compound 3 with Sulfinyl Halide 5 having substituent R.sup.1. The
conditions for the reaction are the same as those of the above Step
B.
[0153] Step D
[0154] Compound (I-B) obtained in Step C is oxidized by the usual
method to give Compound (I-A) wherein n is 2. m-Chloroperbenzoic
acid, peracetic acid, hydrogen peroxide, trifluoroperacetic acid,
sodium periodate, sodium hypochlorite, potassium permanganate etc.
can be used as an oxidizer and the reaction may be carried out at
0.degree. C. to 50.degree. C. Examples of solvents are
tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane,
toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl
acetate, butyl acetate, pentane, heptane, dioxane, acetone,
acetonitrile, water, methanol, ethanol, isopropanol and mixture
thereof.
[0155] In case X is heterocyclediyl containing at least one N atom
and the N atom connects to CONR.sup.7-Z in the compound (I), the
following reaction may be employed to obtain Compound (I-A') or
(I-B'). Step D may be carried out just after Step C or Step E.
27
[0156] wherein R is lower alkyl or aryl and L is a leaving
group.
[0157] Step C
[0158] Compound 5 is reacted with Compound 6 in a similar manner to
the above Step C to give Compound 7.
[0159] Step E
[0160] Thus obtained Compound 7 is treated with a base in a
suitable solvent to give Compound 8. For example, barium hydroxide,
sodium hydroxide, potassium hydroxide, hydrazine or lithium
propanethiolate.sub.=can be used as a base. As a solvent,
tetrahydrofuran, dimethylformamide, dioxane, acetone, acetonitrile,
methanol, ethanol, propanol, water, the mixture thereof or the like
can be used. The reaction can be carried out at 0.degree. C. to
100.degree. C. for several minutes to several tens hours.
[0161] Step F
[0162] Compound 8 is reacted with Compound 9 having a leaving group
and a desired substituent in a suitable solvent in the presence or
absence of a base at 0.degree. C. to 100.degree. C. for several
minutes to several days to give Compound (I-B'). Examples of the
leaving group are phenoxy, chloro and trichloromethyl. Examples of
the base are triethylamine, pyridine, diisopropylethylamine, sodium
hydroxide, potassium carbonate and sodium hydrogencarbonate.
Examples of the solvent are tetrahydrofuran, dimethylformamide,
diethyl ether, dichloromethane, toluene, benzene, xylene,
cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate,
pentane, heptane, dioxane, acetone, acetonitrile, methanol, ethanol
and the mixture thereof.
[0163] Step D
[0164] Compound (I-B') is reacted in a similar manner to the above
Step D to give Compound (I-A').
[0165] (Compound wherein Y.dbd.NR.sup.7CO) 28
[0166] wherein each of the symbols is the same as the above.
[0167] Step G and Step B
[0168] Compound 10 is reacted with Compound 11 under the same
reaction condition as that in Step B. Thus obtained Compound 12 is
reacted in a similar manner to the above Step B to give Compound
(I-C) wherein n=2.
[0169] Step C and Step D
[0170] To synthesize Compound (I-D), Compound 12 obtained in Step G
may be reacted in similar manners to the above Step C and Step
D.
[0171] (Compound wherein Y.dbd.OCONR.sup.7) 29
[0172] wherein each of symbols is the same as the above.
[0173] Step H
[0174] Compound 13 is reacted with Isocianate Compound 14 having a
substituent Z in a suitable solvent in the presence or absence of a
suitable catalyst at 0.degree. C. to 100.degree. C. for several
minutes to several days to give Compound 15. Examples of the
solvent are tetrahydrofuran, dimethylformamide, diethyl ether,
dichloromethane, toluene, benzene, xylene, cyclohexane, hexane,
chloroform, ethyl acetate., butyl acetate, pentane, heptane,
dioxane, acetone, acetonitrile and the mixture thereof.
[0175] Step C and Step D
[0176] Thus obtained Compound 15 is reacted in similar manners to
Step C and Step D to give Compound (I-E) of the present
invention.
[0177] (Compound wherein Y.dbd.CSNR.sup.7 or NR.sup.7CS)
[0178] Compound (I) wherein Y is CSNR.sup.7 or NR.sup.7CS can be
synthesized by reacting Compound (I) wherein Y is CONR.sup.7 or
NR.sup.7CO synthesized in any one of the above methods with the
Lawesson's reagent or phosphorus pentasulfide in a suitable solvent
at 30.degree. C. to 100.degree. C. for several minutes to several
hours. Examples of the solvent are tetrahydrofuran,
dimethylformamide, diethyl ether, dichloromethane, toluene,
benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate,
butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile and
the mixture thereof.
[0179] Amino groups may be protected with a suitable protecting
group in the usual manner at a suitable step. For example,
phthalimide, lower alkoxycarbonyl, lower alkenyloxycarbonyl,
halogenoalkoxycarbonyl, aryl(lower)alkoxycarbonyl, trialkylsilyl,
lower alkylsulfonyl, halogeno(lower)alkylsulfonyl, arylsulfonyl,
lower alkylcarbonyl and arylcarbonyl can be used as the protecting
group.
[0180] After protection of the amino group, the compound is
subjected to the above-mentioned reactions and the obtained
compound is deprotected by treatment of an acid or a base in a
suitable solvent at a suitable stage. Examples of a solvent is
tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane,
toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl
acetate, butyl acetate, pentane, heptane, dioxane, acetone,
acetonitrile and the mixture thereof. Examples of a base are
hydrazine, pyridine, sodium hydroxide and potassium hydroxide and
examples of an acid are hydrochloric acid, trifluoroacetic acid and
hydrofluoric acid.
[0181] All of the compounds of the present invention have an NPY Y5
antagonistic activity and the following compounds are specifically
preferable.
[0182] In the formula (I),
[0183] a compound wherein R.sup.1 is optionally substituted lower
alkyl or optionally substituted cycloalkyl (hereinafter referred to
as "R.sup.1 is R1-1"),
[0184] a compound wherein R.sup.1 is C3 to C10 alkyl or C5 to C6
cycloalkyl, each of which is optionally substituted with halogen
(hereinafter referred to as "R.sup.1 is R1-2"),
[0185] a compound wherein R.sup.1 is C3 to C10 alkyl optionally
substituted with halogen (hereinafter referred to as "R.sup.1 is
R1-3"),
[0186] a compound wherein R.sup.1 is isopropyl or t-butyl
(hereinafter referred to as "R.sup.1 is R1-4"),
[0187] a compound wherein R.sup.2 is hydrogen or C1 to C3 alkyl
(hereinafter referred to as "R.sup.2 is R2-1"),
[0188] a compound wherein R.sup.2 is hydrogen (hereinafter referred
to as"R.sup.2 is R2-2"),
[0189] a compound wherein X is optionally substituted lower
alkylene, optionally substituted lower alkenylene or 30
[0190] wherein 31
[0191] is optionally substituted cycloalkylene, optionally
substituted cycloalkenylene, optionally substituted
bicycloalkylene, optionally substituted phenylene or optionally
substituted heterocyclediyl (hereinafter referred to as "X is
X-1").
[0192] a compound wherein X is C2 to C6 alkylene, C3 to C6
alkenylene or 32
[0193] wherein 33
[0194] is optionally substituted cycloalkylene, optionally
substituted cycloalkenylene, optionally substituted
bicycloalkylene, optionally substituted phenylene,
[0195] optionally substituted piperidinylene, optionally
substituted thiophenediyl or optionally substituted furandiyl
(hereinafter referred to as "X is X-2"),
[0196] a compound wherein X is C2 to C6 alkylene or 34
[0197] wherein is optionally substituted cycloalkylene, optionally
substituted phenylene,
[0198] optionally substituted piperidinylene, optionally
substituted thiophenediyl or optionally substituted furandiyl
(hereinafter referred to as "X is X-3"),
[0199] a compound wherein X is (i) C2 to C6 alkylene or (ii)
cycloalkylene or phenylene, each of which is optionally substituted
with halogen, hydroxy, lower alkyl or
[0200] halogeno(lower)alkyl (hereinafter referred to as "X is
X-4"),
[0201] a compound wherein X is C2 to C6 alkylene or to C5 to C6
cycloalkylene (hereinafter referred to as "X is X-5"),
[0202] a compound wherein X is C3 to C6 alkylene or
1,4-cyclohexylene (hereinafter referred to as "X is X-6"),
[0203] a compound wherein Y is CONR.sup.7, CSNR.sup.7, NR.sup.7CO
or NR.sup.7CS and R.sup.7 is hydrogen or C1 to C3 alkyl
(hereinafter referred to as "Y is Y-1"),
[0204] a compound wherein Y is CONH, CSNH or NHCO (hereinafter
referred to as "Y is Y-2"),
[0205] a compound wherein Y is CONH (hereinafter referred to as "Y
is Y-3"),
[0206] a compound wherein Z is optionally substituted lower alkyl,
optionally substituted carbocyclyl or optionally substituted
heterocyclyl (hereinafter referred to as "Z is Z-1"),
[0207] a compound wherein Z is
--(CR.sup.8R.sup.9)r-W--(CR.sup.10OR.sup.11- )s-V
[0208] wherein R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each
independently hydrogen or lower alkyl and when Z has two or more of
R.sup.8, two or more of R.sup.9, two or more of R.sup.10 and/or two
or more of R.sup.11, each of R.sup.8, R.sup.9, R.sup.10 and
R.sup.11 may be different, W is single bond, O, S or NR.sup.12;
R.sup.12 is hydrogen, lower alkyl or phenyl, V is hydrogen,
optionally substituted cycloalkyl, optionally substituted
bicycloalkyl, optionally substituted aryl or optionally substituted
heterocyclyl, r is an integer of 1 to 4 and s is an integer of 0 to
4
[0209] (hereinafter referred to as "Z is Z-2"),
[0210] a compound wherein Z is --(CH.sub.2)r-W--(CH.sub.2)s-V
[0211] wherein W is single bond, O, S or NR.sup.12, R.sup.12 is
hydrogen or lower alkyl, V is optionally substituted aryl or
optionally substituted heterocyclyl wherein the substituents is
halogen, hydroxy, lower alkyl, halogeno(lower)alkyl, lower alkoxy,
lower alkenyl, amino, lower alkylamino, acyl, carboxy, lower
alkoxycarbonyl, phenyl or monocyclic heteroaryl, r is an integer of
1 to 4 and s is an integer of 0 to 4
[0212] (hereinafter referred to as "Z is Z-3),
[0213] a compound wherein Z is --(CH.sub.2)r-W--(CH.sub.2)s-V
[0214] wherein W is single bond, O, S, NH or NMe, V is optionally
substituted phenyl or optionally substituted heteroaryl wherein the
substituents is halogen, lower alkyl, halogeno(lower)alkyl, lower
alkoxy, amino or lower alkylamino, r is an integer of 1 to 3 and s
is an integer of 0 or 1
[0215] (hereinafter referred to as "Z is Z-4"),
[0216] a compound wherein Z is optionally substituted
carbocyclyl,
[0217] wherein the substituent is halogen; hydroxy:
[0218] optionally substituted lower alkyl wherein the substituents
is halogen, hydroxy, carboxy, lower alkoxycarbonyl, cyano and/or
phenyl;
[0219] lower alkenyl optionally substituted with lower
alkoxycarbonyl;
[0220] optionally substituted lower alkoxy wherein the substituents
is halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl,
lower alkylamino, cycloalkyl, cyano and /or heterocyclyl;
[0221] cycloalkyl; cycloalkyloxy; acyl; lower alkylthio; carbamoyl;
lower alkylcarbamoyl;
[0222] cycloalkylcarbamoyl; hydroxy imino;
[0223] optionally substituted amino wherein the substituents is
lower alkyl, optionally protected hydroxy(lower)alkyl, lower
alkoxy(lower)alkyl, acyl, lower alkylsulfonyl, arylsulfonyl and/or
phenyl;
[0224] phenyl optionally substituted with halogen, cyano, phenyl
and/or heterocyclyl;
[0225] lower alkylsulfinyl; lower alkylsulfamoyl;
cycloalkylsulfamoyl;
[0226] nitro; cyano; alkylenedioxy; phenylazo optionally
substituted with lower alkyl; phenoxy; oxo;
[0227] optionally substituted heterocyclyl wherein the substituents
is optionally protected hydroxy, mercapto, halogen, lower alkyl,
cycloalkyl, lower alkoxycarbonyl, acyl, amino, lower
alkoxycarbonylamino, carbamoyl, oxo, phenyl, lower alkoxyphenyl,
halogenophenyl, heterocyclyl and/or oxo;
[0228] heterocyclylsulfonyl optionally substituted with lower
alkyl; heterocyclyloxy;
[0229] heterocyclylcarbonyl optionally substituted with lower
alkyl
[0230] (hereinafter referred to as "Z is Z-5);
[0231] a compound wherein Z is optionally substituted phenyl
[0232] wherein the substituents is halogen: hydroxy; lower alkyl
optionally substituted with halogen, hydroxy, lower alkoxycarbonyl,
cyano and/or phenyl; lower alkoxycarbonyl(lower)alkenyl; lower
alkoxy optionally substituted with halogen, lower alkoxy, lower
alkoxycarbonyl, cycloalkyl and/or heterocyclyl; cycloalkyl:
[0233] cycloalkyloxy; acyl; lower alkylthio; carbamoyl; lower
alkycarbamoyl; amino optionally substituted with lower alkyl,
hydroxy(lower)alkyl, acyl, lower alkylsulfonyl and/or phenyl;
phenyl optionally substituted with halogen, cyano, phenyl and/or
heterocyclyl;
[0234] lower alkyl sulfamoyl; cycloalkylsulfamoyl; nitro;
alkylenedioxy; phenylazo optionally substituted with lower alkyl;
phenoxy; oxo;
[0235] heterocyclyl optionally substituted with hydroxy, halogen,
lower alkyl, lower alkoxycarbonyl, amino, carbamoyl, phenyl,
halogenophenyl, heterocyclyl and/or oxo;
[0236] heterocyclyloxy; and/or heterocyclylsulfonyl optionally
substituted with lower alkyl
[0237] (hereinafter referred to as "Z is Z-6"),
[0238] a compound wherein Z is optionally substituted phenyl
[0239] wherein the substituents is halogen; lower alkyl optionally
substituted with halogen, hydroxy, lower alkoxycarbonyl and/or
phenyl; lower alkoxy optionally substituted with halogen and/or
cycloalkyl; cycloalkyl; cycloalkyloxy; acyl; lower alkylthio; lower
alkylcarbamoyl; amino optionally substituted with lower alkyl,
hydroxy(lower)alkyl, acyl and/or phenyl; phenyl optionally
substituted with piperidyl; cycloalkylsulfamoyl;
[0240] alkylenedioxy; phenoxy;
[0241] morpholinyl or morpholino, each of which is optionally
substituted with lower alkyl;
[0242] piperidyl optionally substituted with hydroxy, lower alkyl,
lower alkoxycarbonyl, phenyl, halogenophenyl and/or oxo;
pyrrolidinyl optionally substituted with hydroxy, carbamoyl and/or
oxo;
[0243] piperazinyl optionally substituted with phenyl or
pyrimidinyl: dihydropyridyl;
[0244] pyrrolyl; pyrrolinyl; imidazolyl optionally substituted with
halogen and/or lower alkyl;
[0245] pyrazolyl; thienyl; thiadiazolyl; furyl; oxazolyl;
isoxazolyl; tetrazolyl optionally substituted with lower alkyl
and/or phenyl; indolinyl; indolyl; tetrahydroquinolyl;
[0246] benzothiazolyl optionally substituted with lower alkyl;
tetrahydroisothiazolyl optionally substituted with oxo;
benzopyranyl optionally substituted with oxo;
[0247] tetrahydropyranyloxy; tetrahydrofuryloxy; morpholinosulfonyl
optionally substituted with lower alkyl; and/or piperidylsulfonyl
optionally substituted with lower alkyl
[0248] hereinafter referred to as "Z is Z-7"),
[0249] a compound wherein Z is optionally substituted phenyl
[0250] wherein the substituents is halogen, lower alkyl,
halogeno(lower)alkyl, lower alkoxy, cycloalkyloxy, lower
alkylcarbamoyl, phenyl, lower alkyl morpholino and/or
tetrahydropyranyloxy
[0251] (hereinafter referred to as "Z is Z-8"),
[0252] a compound wherein Z is optionally substituted
heterocyclyl
[0253] wherein the substituents is halogen, hydroxy, lower alkyl,
halogeno(lower)alkyl, lower alkoxy, mercapto, lower alkylthio,
acyl, carboxy, lower alkoxycarbonyl, amino, lower alkylamino,
phenyl, naphthyl, phenylthio optionally substituted with halogen,
phenoxy optionally substituted with halogen, oxo, and/or
heterocyclyl optionally substituted with lower alkyl
[0254] (hereinafter referred to as "Z is Z-9"),
[0255] a compound wherein Z is thienyl, pyrazolyl, thiazolyl,
thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl,
isoindolyl, indolinyl, isoindolinyl, indazolyl, benzopyranyl,
benzoxazolyl, benzothienyl, benzothiazolyl, benzothiazolinyl,
benzothiadiazolyl, quinolyl, isoquinolyl, dihydrobenzofuryl,
carbazolyl, acridinyl or dibenzofuryl, each of which is optionally
substituted with substituents selected from the group of lower
alkyl;
[0256] halogeno(lower)alkyl; lower alkoxy; lower alkoxycarbonyl:
acyl; lower alkoxycarbonyl(lower)alkyl; mercapto: phenyl, naphthyl,
phenylthio or phenoxy, each of which is optionally substituted with
halogen; furyl; nitro; oxo; and morpholino optionally substituted
with lower alkyl) (hereinafter referred to as "Z is Z-10"),
[0257] a compound wherein Z is thienyl, thiazolyl, thiadiazolyl,
pyridyl, pyrazinyl, indolyl, isoindolinyl, benzopyranyl, quinolyl,
carbazolyl, dibenzofuryl, benzopyranyl, benzothienyl or
benzothiazolyl, each of which is optionally substituted with one or
more substituents selected from the group of lower alkyl,
halogeno(lower)alkyl, lower alkoxy, lower alkoxycarbonyl, acyl,
phenyl, naphthyl, phenylthio, lower alkyl morpholino and oxo)
(hereinafter referred to as "Z is Z-11),
[0258] a compound wherein R.sup.1 is R1-2, R.sup.2 is R2-2, n is 2
and a combination of X, Y and Z, i.e., (X, Y, Z), is any one of the
followings.
[0259] (X, Y, Z)=(X-3, Y-2, Z-1), (X-3, Y-2, Z-2), (X-3, Y-2, Z-3),
(X-3, Y-2, Z-4), (X-3, Y-2, Z-5), (X-3, Y-2, Z-6), (X-3, Y-2, Z-7),
(X-3, Y-2, Z-8), (X-3, Y-2, Z-9), (X-3, Y-2, Z-10), (X-3, Y-2,
Z-11),
[0260] (X-3, Y-3, Z-1), (X-3, Y-3, Z-2), (X-3, Y-3, Z-3), (X-3,
Y-3, Z-4), (X-3, Y-3, Z-5), X-3, Y-3, Z-6), (X-3, Y-3, Z-7), (X-3,
Y-3, Z-8), (X-3, Y-3, Z-9), (X-3, Y-3, Z-10), (X-3, Y-3, Z-11),
(X-4, Y-2, Z-1), (X-4, Y-2, Z-2), (X-4, Y-2, Z-3), (X-4, Y-2, Z-4),
(X-4, Y-2, Z-5), (X-4, Y-2, Z-6), (X-4, Y-2, Z-7), (X-4, Y-2, Z-8),
(X-4, Y-2, Z-9), (X-4, Y-2, Z-10), (X-4, Y-2, Z-11), (X-4, Y-3,
Z-1), (X-4, Y-3, Z-2), (X-4, Y-3, Z-3), (X-4, Y-3, Z-4), (X-4, Y-3,
Z-5), (X-4, Y-3, Z-6), (X-4, Y-3, Z-7), (X-4, Y-3, Z-8), (X-4, Y-3,
Z-9), (X-4, Y-3, Z-10), (X-4, Y-3, Z-11), (X-5, Y-2, Z-1), (X-5,
Y-2, Z-2), (X-5, Y-2, Z-3), (X-5, Y-2, Z-4), (X-5, Y-2, Z-5), (X-5,
Y-2, Z-6), (X-5, Y-2, Z-7), (X-5, Y-2, Z-8), (X-5, Y-2, Z-9), (X-5,
Y-2, Z-10), (X-5, Y-2, Z-11), (X-5, Y-3, Z-1), (X-5, Y-3, Z-2),
(X-5, Y-3, Z-3), (X-5, Y-3, Z-4), (X-5, Y-3, Z-5), (X-5, Y-3, Z-6),
(X-5, Y-3, Z-7), (X-5, Y-3, Z-8), (X-5, Y-3, Z-9), (X-5, Y-3, Z-10)
or (X-5, Y-3, Z-11),
[0261] the pharmaceutically acceptable salt, solvate or prodrug
thereof.
[0262] The NPY Y5 receptor antagonist of the present invention is
effective for all of the diseases in which NPY Y5 is involved and
it is especially useful for preventing and/or treating obesity and
suppressing food intake. Moreover, the antagonist is effective for
preventing and/or treating the diseases in which obesity acts as a
risk factor, for example, diabetes, hypertension, hyperlipemia,
atherosclerosis and acute coronary syndrome.
[0263] In addition, the NPY Y5 receptor antagonist of the present
invention has a low affinity for NPY Y1 and Y2 receptors, and has a
high selectivity for NPY Y5 receptor. NPY causes a sustained
vasoconstrictive action in the periphery and this action is mainly
via Y1 receptor. Since Y5 receptor is not involved in this action
at all, the NPY Y5 receptor antagonist has a low risk of inducing
side effects based on the peripheral vasoconstriction, and is
expected to be suitably used as a safe medicine.
[0264] The NPY Y5 receptor antagonist shows an anti-obestic effect
by suppressing food intake. Therefore, it is one of the features
that this antagonist does not induce side effects, e.g., an
indigestion caused by an anti-obestic agent which inhibits
digestion and absorption, and a central side effect such as
anti-depression caused by a serotonin transporter inhibitor showing
an anti-obesity effect.
[0265] A compound of the present invention can be administered
orally or parenterally as an anti-ob agent agent. In the case of
oral administration, it may be in any usual form such as tablets,
granules, powders, capsules, pills, solutions, syrups, buccal
tablets and sublingual tablets. When the compound is parenterally
administered, any usual form is preferable, for example, injections
(e.g., intravenous, intramuscular), suppositories, endermic agents
and vapors. Oral administration is particularly preferable because
the compounds of the present invention show a high oral
absorbability.
[0266] A pharmaceutical composition may be manufactured by mixing
an effective amount of a compound of the present invention with
various pharmaceutical additives suitable for the administration
form, such as excipients, binders, moistening agents,
disintegrators, lubricants and diluents. When the composition is of
an injection, an active ingredient together with a suitable carrier
can be sterilized to give a pharmaceutical composition.
[0267] Examples of the excipients include lactose, saccharose,
glucose, starch, calcium carbonate and crystalline cellulose.
Examples of the binders include methylcellulose,
carboxymethylcellulose, hydroxypropylcellulose, gelatin and
polyvinylpyrrolidone. Examples of the disintegrators include
carboxymethylcellulose, sodium carboxymethylcellulose, starch,
sodium alginate, agar and sodium lauryl sulfate. Examples of the
lubricants include talc, magnesium stearate and macrogol. Cacao
oil, macrogol, methylcellulose etc. may be used as base materials
of suppositories. When the composition is manufactured as
solutions, emulsified injections or suspended injections,
dissolving accelerators, suspending agents, emulsifiers,
stabilizers, preservatives, isotonic agents and the like may be
added. For oral administration, sweetening agents, flavors and the
like may be added.
[0268] Although the dosage of a compound of the present invention
as an anti-obestic agent or anorectic agent should be determined in
consideration of the patient's age and body weight, the type and
degree of diseases, the administration route etc., a usual oral
dosage for an adult is 0.05 to 100 mg/kg/day and preferable is 0.1
to 10 mg/kg/day. For parenteral administration, although the dosage
highly varies with administration routes, a usual dosage is 0.005
to 10 mg/kg/day, preferably, 0.01 to 1 mg/kg/day. The dosage may be
administered in one to several divisions per day.
[0269] The present invention is further explained by the following
Examples and Experiments, which are not intended to limit the scope
of the present invention.
EXAMPLES
Example 1
Synthesis of Compound (I-7)
[0270] 35
[0271] Sodium carbonate (995 mg, 9.38 mmol) was dissolved in 30 ml
of water and starting material amino acid (1.0 g, 8.53 mmol) and
N-carbethoxyphthalimide (2.49 g, 11.4 mmol) were added thereto. The
mixture was stirred at room temperature overnight. The pH of the
mixture was adjusted to 1 by adding conc. hydrochloric acid.
Precipitated crystals were washed with water and dried to give the
desired compound (1.72 g 82% yield).
[0272] .sup.1H-NMR (CD.sub.3OD) .delta. ppm: 1.59-1.77 (m, 4H),
2.34 (t, 2H, J=6.3 Hz), 3.69 (t, 2H, J=6.6 Hz), 7.78-7.87 (m, 4H).
36
[0273] The compound obtained in Step 1 (1.0 g, 4.0 mmol) was
dissolved in 5 ml of dichloromethane at room temperature. Oxalyl
chloride (0.459 ml, 5.2 mmol) and trace amounts of DMF were added
to the mixture under ice-cooling and the mixture was reacted under
ice-cooling and at room temperature, each for 30 min. After the
solvent was removed under reduced pressure, 5 ml of dichloromethane
was added. Under ice-cooling, 4-butylaniline (664 mg, 4.4 mmol) and
triethylamine (0.564 ml. 4.4 mmol) were added thereto and the
mixture was reacted for 30 min. at room temperature. The reactant
was poured into water and extracted with chloroform. The organic
layer was washed with water and dried over magnesium sulfate
anhydride. The solvent was removed under reduced pressure and the
residue was purified by silica gel chromatography to give the
desired compound (1.49 g, 97% yield).
[0274] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.5
Hz), 1.27-1.39 (m, 2H), 1.51-1.62 (m, 2H), 1.72-1.84 (m, 4H),
2.40-2.46 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.76 (t, 1H, J=5.7 Hz),
7.12 (d, 2H, J=7.8 Hz), 7.33 (s, 1H), 7.42 (d, 2H, J=8.1 Hz),
7.71-7.73 (m, 2H), 7.83-7.86 (m, 2H). 37
[0275] After the compound obtained in Step 2 (1.49 g, 3.9 mmol) was
dissolved in 30 ml of ethanol, hydrazine monohydrate (0.591 mg,
11.8 mmol) was added and the mixture was reacted at 50.degree. C.
for 3 hours. The solvent was removed, 1 mol/l aqueous NaOH was
added and the solution was extracted with ethyl acetate. The
organic layer was washed with water and dried over magnesium
sulfate anhydride. The solvent was removed under reduced pressure
to give the desired compound (808 mg, 83% yield)
[0276] .sup.1H-NMR (CD.sub.3OD) .delta. ppm: 0.93 (t, 3H, J=7.2
Hz), 1.28-1.40 (m, 2H), 1.50-1.62 (m, 4H), 1.67-1.77 (m, 2H), 2.37
(t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 2.68 (t, 2H, J=7.2 Hz),
7.11 (d, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8.4 Hz).
[0277] Step 4 38
[0278] The compound obtained in Step 3 (808 mg, 3.25 mmol) was
suspended in 5 ml of dichloromethane under ice-cooling and
isopropylsulfonyl chloride (696 mg, 4.9 mmol) and triethylamine
(494 mg, 4.9 mmol) were added. After the mixture was reacted under
ice-cooling for an hour, the reactant was poured into water and
extracted with chloroform. The organic layer was washed with water
and dried over magnesium sulfate anhydride. The solvent was removed
under reduced pressure and the residue was purified by silica gel
chromatography to give the desired compound quantitatively.
[0279] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.2
Hz), 1.27-1.40 (m, 2H), 1.36 (d, 6H, J=6.6 Hz), 1.51-1.69 (m, 4H),
1.77-1.86 (m, 2H), 2.38 (t, 2H, J=7.2 Hz), 2.56 (t, 2H, J=7.5 Hz),
3.12-3.21 (m, 3H), 4.38 (t, 1H, J=5.7 Hz), 7.11 (d, 2H, J=8.4 Hz),
7.36-7.41 (m, 3H).
Example 2
Synthesis of Compound (I-10)
[0280] 39
[0281] The desired compound was synthesized in a similar manner to
Step 4 in Example 1 except that tert-butylsulfinyl chloride (689
mg, 4.9 mmol) and triethylamine (494 mg, 4.9 mmol) were added to
the compound obtained in Step 3 in Example 1.
[0282] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.5
Hz), 1.22 (s, 9H), 1.30-1.37 (m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86
(m, 2H), 2.31-2.40 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.15-3.26 (m,
3H), 7.11 (t, 2H, J=8.7 Hz), 7.42 (d, 2H, J=8.1 Hz), 7.54 (s,
1H).
Example 3
Synthesis of Compound (I-11)
[0283] 40
[0284] The compound obtained in Example 2 (352 mg, 1.0 mmol) was
dissolved in 5 ml of dichloromethane under ice-cooling and mCPBA
(259 mg, 1.5 mmol) was added to the solution. The solution was
reacted at room temperature for an hour and the insoluble material
was filtered off. The filtrate was washed with 1 mol/l NaOH,
Na.sub.2S.sub.2O.sub.5 and water, successively, and (tried over
magnesium sulfate anhydride. The solvent was removed under reduced
pressure and the residue was purified by silica gel chromatography
to give the desired compound (338 mg, 92% yield).
[0285] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.5
Hz), 1.29-1.39 (m, 2H), 1.39 (s, 9H), 1.51-1.68 (m, 4H), 1.76-1.84
(m, 2H), 2.37 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.19-3.26
(m, 2H), 4.20 (t, 1H, J=5.7 Hz), 7.11 (t, 2H, J=8.1 Hz), 7.42 (d,
2H, J=8.7 Hz), 7.46 (s, 1H).
Example 4
Synthesis of Compound (I-72)
[0286] 41
[0287] Starting material amino acid (a mixture of cis isomer and
trans isomer) (1.0 g, 8.53 mmol) was dissolved in 7.5 ml of
methanol. Thionyl chloride (1.0 ml, 13.7 mmol) was added to the
mixture under ice-cooling and the mixture was stirred at room
temperature overnight. After the mixture was concentrated under
reduced pressure, diethylether was added and precipitated crystals
were obtained by filtration. The crystals were washed with
diethylether and dried to give the desired compound (1.25 g, 93%
yield).
[0288] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.50-2.60 (m, 9H),
3.08-3.36 (m, 1H), 3.67 (s, 3H, CO.sub.2Me of cis isomer), 3.71 (s,
3H, CO.sub.2Me of trans isomer), 8.15-8.55 (m, 3H). 42
[0289] The desired sulfonamide (a mixture of cis isomer and trans
isomer) was synthesized from starting material methyl ester in
similar manners to Step 3 in Example 1 and Example 2.
[0290] cis isomer
[0291] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.39 (s, 9H),
1.52-1.99 (m, 8H), 2.43-2.53 (m, 1H), 3.42-3.55 (m, 1H), 3.69 (s,
3H), 3.85 (d, 1H, J=9.0 Hz). 43
[0292] Starting material sulfonamide (19.4 g, 70.0 mmol, a mixture
of cis isomer and trans isomer) was dissolved in 30 ml of methanol.
To the mixture, 28% sodium methoxide 4 ml, 140.0 mmol) was added
and refluxed with stirring under ice-cooling. After the solvent was
removed, the residue was diluted with chloroform, and 1 mol/l HCl
was added with stirring under ice-cooling until pH of an aqueous
layer reached 3. The aqueous layer was extracted with chloroform
and the organic layer was washed with water and dried over
magnesium sulfate anhydride. The obtained crude crystals were
recrystallized from hexane-ethyl acetate to give the desired
sulfonamide (trans isomer, 7.75 g, 40% yield).
[0293] trans isomer
[0294] .sup.1H-NMR (CD.sub.3OD) .delta. ppm: 1.16-1.32 (m, 2H),
1.39 (s, 9H), 1.44-1.52 (m, 2H), 1.98-2.09 (m, 2H), 9.14-2.29 (m,
3H), 3.18-3.37 (m, 1H), 3.63 (d, 1H, J=9.0 Hz), 3.67 (s, 3H).
44
[0295] Starting material methyl ester (4.77 g, 17.2 mmol) was
dissolved in 95 ml of methanol and 1 mol/l NaOH (43 ml, 43.0 mmol)
was added with stirring under ice-cooling. The mixture was stirred
at room temperature overnight and concentrated under reduced
pressure. After 1 mol/l HCl was added with stirring until pH of the
mixture reached 3 under ice-cooling, the precipitated crystals were
collected by filtration, washed with water and dried. The obtained
crude crystals were recrystallized from hexane-ethylacetate to give
the desired carboxylic acid (4.20 g, 93% yield).
[0296] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.18-1.35 (m, 2H),
1.39 (s, 9H), 1.46-1.63 (m, 2H), 2.01-2.14 (m, 2H), 2.14-2.32 (m,
3H), 3.18-3.35 (m, 1H), 3.80 (d, 1H, J=9.6 Hz). 45
[0297] A starting material carboxylic acid (5.86 g, 22.3 mmol) was
dissolved in 88 ml of dichloromethane at room temperature. To the
mixture, oxalyl chloride (2.34 ml, 26.7 mmol) and catalytic amount
of DMF were added under ice-cooling and stirred at room temperature
for an hour. After the solvent was removed under reduced pressure,
dichloromethane (115 ml), substituted aniline (5.05 g, 24.5 mmol)
and triethylamine (4.65 ml, 33.4 mmol) were added. The mixture was
stirred at room temperature for 2.5 hours, the ice-cooling water
was poured thereto, and the mixture was extracted with chloroform.
An organic layer was washed with water and dried over magnesium
sulfate anhydride. The solvent was removed under reduced pressure
and ethyl acetate and hexane were added to the residue. The
precipitated crystals were collected with filtration to give the
desired amide (7.00 g, 70% yield).
[0298] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.25 (d, 6H, J=6.3
Hz), 1.17-1.42 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.43
(m, 7H), 3.20-3.43 (m, 3H), 3.67 (d, 1H, J=9.6 Hz), 3.74-3.86 (m,
2H), 6.86 (d, 2H, J=9.0 Hz), 7.04 (s, 1H), 7.38 (d, 2H, J=9.0
Hz).
Example 5
Synthesis of Compound (I-2)
[0299] 46
[0300] After starting material diamine (461 mg, 2.5 mmol) was
suspended in dichloromethane under ice-cooling, an acid chloride
(500 mg, 2.5 mmol) and triethylamine (773 mg, 7.5 mmol) were added
and the mixture was reacted for 30 min. Water and dichloromethane
were added to the reactant and insoluble materials were filtered
off. The organic layer was washed with water and dried over
magnesium sulfate anhydride. The solvent was removed under reduced
pressure to give the desired compound as a residue (100 mg, 15%
yield).
[0301] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.93 (t, 3H, J=7.2
Hz), 1.30-1.42 (m,, 2H), 1.57-1.67 (m, 2H), 2.66 (t, 2H, J=7.8 Hz),
3.50 (brs, 1H), 6.57 (s, 1H), 6.68 (d, 2H, J=8.7 Hz), 7.26 (d, 2H,
J=8.4 Hz), 7.39 (d, 2H, J=8.7 Hz), 7.68 (s, 1H), 7.75 (d, 2H, J=8.1
Hz). 47
[0302] The desired compound was synthesized in a similar manner to
Step 4 in Example 1.
[0303] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.94 (t, 3H, J=7.5
Hz), 1.34-1.44 (m, 2H), 1.40 (d, 6H, J=6.6 Hz), 1.59-1.68 (m, 2H),
2.69 (t, 2H, J=7.8 Hz), 3.24-3.35 (m, 1H), 6.49 (s, 1H), 7.23-7.32
(m, 4H), 7.6 (d, 2H, J=8.7 Hz), 7.79 (d, 2H, J=8.1 Hz), 7.85 (s,
1H).
Example 6
Synthesis of Compound (I-31)
[0304] 48
[0305] A starting material diamine (8.37 g, 73.3 mmol) was
dissolved in 30 ml of dioxane at room temperature and a solution of
Boc.sub.2O (2 g, 9.2 mmol) in dioxane (30 ml) was added. The
mixture was reacted at room temperature for 3 days and the solvent
was removed. Water was added to the residue and the mixture was
extracted with chloroform. The organic layer was washed with water
and dried over magnesium sulfate anhydride. The solvent was removed
under reduced pressure to give the desired compound as a residue
(1.8 g, 92% yield based on Boc.sub.2O)
[0306] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.07-1.26 (m, 6H),
1.44 (s, 9H), 1.84-2.00 (m, 4H), 2.58-2.67 (m, 1H), 3.37 (brs, 1H),
4.43 (brs, 1H). 49
[0307] The desired compound was synthesized in a similar manner to
Step 1 in Example 5.
[0308] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.92 (t, 3H, J=7.2
Hz), 1.26-1.42 (m, 6H), 1.45 (s, 9H), 1.54-1.68 (m, 2H), 1.99-2.12
(m, 4H), 2.64 (t, 2H, J=7.8 Hz), 3.43 (brs, 1H), 3.90-4.00 9m, 1H),
4.48 (d, 1H, J=5.7 Hz), 5.95 (d, 1H, J=8.4 Hz), 7.21 (d, 2H, J=8.4
Hz), 7.65 (d, 2H, J=8.4 Hz). 50
[0309] A starting material Boc compound (2.08 g, 5.55 mmol) was
dissolved in 20 ml of ethyl acetate under ice-cooling and 20 ml of
4 mol/l HCl/AcOEt was added. The mixture was reacted at room
temperature for an hour and the solvent was removed under reduced
pressure to give the desired compound as a residue (1.7 g, 98%
yield).
[0310] .sup.1H-NMR (CD.sub.3OD) .delta. ppm: 0.93 (t, 3H, J=7.2
Hz), 1.29-1.41 (m, 2H), 1.50-1.66 )m, 6H), 2.02-2.18 (m, 4H), 2.66
(t, 2H, J=7.8 Hz), 3.13 (brs, 1H), 3.82-3.94 (m, 1H), 7.26 (d, 2H,
J=8.7 Hz), 7.72 (d, 2H, J=8.4 Hz). 51
[0311] The desired compound was synthesized in a similar manner to
Step 4 in Example 1.
[0312] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.92 (t, 3H, J=7.5
Hz), 1.21 (s, 9H), 1.28-1.62 (m, 8H), 2.07-2.14 (m, 4H), 2.64 (t,
2H, J=7.8 Hz), 3.11 (d, 1H, J=5.1 Hz), 3.20 (brs, 1H), 3.90-4.04
(m, 1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H, J=8.1 Hz), 7.67 (t, 2H,
J=8.4 Hz).
Example 7
Synthesis of Compound (I-32)
[0313] 52
[0314] The desired compound was synthesized from the compound
obtained in Example 6 in a similar manner to Example 3.
[0315] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.92 (t, 3H, J=7.2
Hz), 1.27-1.65 (m, 8H), 1.40 (s, 9H), 2.10-2.23 (m, 4H), 2.65 (t,
2H, J=7.5 Hz), 3.23-3.35 (m, 1H), 3.49 (s, 1H), 3.88-4.02 (m, 1H),
5.84-5.92 (m, 1H), 7.13 (t, 2H, J=8.4 Hz), 7.65 (d, 2H, J=8.1
Hz).
Example 8
Synthesis of Compound (I-5)
[0316] 53
[0317] The desired compound was synthesized in a similar manner to
Step 2 in Example 1.
[0318] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.94 (t, 3H, J=7.5
Hz), 1.30-1.42 (m, 2H), 1.50-1.65 (m, 2H), 2.61 (t, 2H, J=7.8 Hz),
7.20 (d, 2H, J=7.2 Hz), 7.48-7.51 (m, 3H), 7.72 (s, 1H), 7.88-7.90
(m, 1H). 54
[0319] To a mixture of a starting material nitro compound (593 mg,
1.95 mmol) and tin (358 mg, 3.0 mmol), 30 ml of 6 mol/l HCl and 6
ml of THF were added and reacted at 50.degree. C. for 3 hours.
After cooling, the solvent was removed and the residue was
neutralized 10% with NaOH and extracted with chloroform. The
organic layer was washed with water and dried over magnesium
sulfate anhydride. The solvent was removed under reduced pressure
and the residue was purified by silica gel chromatography to give
the desired compound (110 mg, 21% yield).
[0320] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.2
Hz), 1.26-1.39 (m, 2H), 1.49.1.59 (m, 2H), 2.50 (t, 2H, J=7.8 Hz),
4.37 (s, 1H), 6.65 (d, 2H, J=8.4 Hz), 6.97 (d, 2H, J=8.4 Hz), 7.14
(d, 1H, J=8.4 Hz), 7.43 (d, 1H, J=8.7 Hz). 55
[0321] The desired compound was synthesized in a similar manner to
Step 4 in Example 1.
[0322] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.92 (t, 3H, J=7.2
Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.9 Hz), 1.53-1.63 (m, 2H),
2.59 (t, 2H, J=7.8 Hz), 3.35-3.44 (m, 1H), 7.15 (d, 2H, J=8.7 Hz),
7.38 (s, 1H), 7.45 (d, 2H, J=8.7 Hz), 7.57 (s, 1H).
Example 9
Synthesis of Compound (I-4)
[0323] 56
[0324] The desired compound was synthesized in a similar manner to
Step 4 in Example 1.
[0325] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.44 (d, 6H, J=6.9
Hz), 3.33-3.43 (m, 1H), 3.88 (s, 9H), 6.24-6.26 (m, 1H), 7.11-7.14
(m, 2H). 57
[0326] The desired compound was synthesized in a similar manner to
Step 4 in Example 4.
[0327] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.44 (d, 6H, J=6.3
Hz), 3.33-3.45 (m, 1H), 6.25-6.28 (m, 1H), 7.27-7.28 (m, 1H), 7.51
(s, 1H). 58
[0328] The desired compound was synthesized in a similar manner to
Step 2 in Example 1.
[0329] .sup.1H-NMR (CD.sub.3OD) .delta. ppm: 0.92 (t, 3H, J=6.9
Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.3 Hz), 1.53-1.63 (m, 2H),
2.53 (t, 2H, J=7.8 Hz), 3-3.43 (m, 1H), 6.27-6.29 (m, 1H),
7.14-7.16 (m, 3H), 7.50 (d, 2H, J=8.4 Hz), 7.90 (s, 1H).
Example 10
Synthesis of Compound (I-28)
[0330] 59
[0331] The desired compound was synthesized in a similar manner to
Step 1 in Example 1.
[0332] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 1.37-1.52 (m, 3H),
1.74-1.79 (m, 2H), 2.07-2.13 (m, 2H), 2.28-2.42 (m, 2H), 3.72-3.81
(m, 1H), 4.09-4.20 (m, 1H), 7.68-7.73 (m, 2H), 7.81-7.85 (m, 2H).
60
[0333] 4-butylphenyl isocyanate (2.85 g, 16.3 mmol) was dissolved
in 30 ml of THF, and a starting material alcohol (1.0 g, 4.08 mmol)
and bis(tributyltin)oxide (972 mg, 1.63 mmol) were added. After the
mixture was stirred overnight, the solvent was removed, water was
added and the solution was extracted with chloroform. The organic
layer was washed with water and dried over magnesium sulfate
anhydride. The solvent was removed under reduced pressure and the
residue was purified by silica gel chromatography to give the
desired compound (332 mg, 19% yield).
[0334] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.92 (t, 3H, J=6.9
Hz), 1.30-1.40 (m, 2H), 1.48-1.6 (m, 4H), 1.79-1.83 (m, 2H),
2.21-2.25 (m, 2H), 2.37-2.50 (m, 2H), 2.57 (t, 2H, J=7.8 Hz),
4.11-4.22 (m, 1H), 4.77-4.87 (m, 1H), 6.49 (s, 1H), 7.11 (d, 2H,
J=8.7 Hz), 7.28 (d, 2H, J=8.7 Hz), 7.69-7.73 (m, 2H), 7.80-7.84 (m,
2H). 61
[0335] The desired compound was synthesized in similar manners to
Step 3 in Example 1 and Example 2.
[0336] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.2
Hz), 1.21 (s, 9H), 1.30-1.62 (m, 8H), 2.08 (d, 4H, J=11.1 Hz), 2.56
(t, 2H, J=7.8 Hz), 3.04 (d, 1H, J=4.8 Hz), 3.20-3.30 (m, 1H),
4.65-4.76 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.7 Hz), 7.26 (d,
2H, J=8.1 Hz).
Example 11
Synthesis of Compound (I-29)
[0337] 62
[0338] The desired compound was synthesized in a similar manner to
Example 3.
[0339] .sup.1H-NMR (CDCl.sub.3) .delta. ppm: 0.91 (t, 3H, J=7.2
Hz), 1.23-1.62 (m, 8H), 1.40 (s, 9H), 2.12 (d, 4H, J=14.4 Hz), 2.56
(t, 2H, J=7.8 Hz), 3.28-3.40 (m, 1H), 3.90 (s, 1H), 4.60-4.73 (m,
1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.4 Hz), 7.25 (d, 2H, J=8.4
Hz).
Example 12
Synthesis of Compound (I-114)
[0340] 63
[0341] Lawesson's reagent
[2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosp-
hetane-2,4-disulfide] (132 ml) was added to a solution of 100 mg of
Compound (I-110) synthesized in a similar manner to Example 1 in
toluene (2.7 ml) and the mixture was stirred at 80.degree. C. for 3
hours. The reactant was concentrated under reduced pressure and the
residue was purified by silica gel chromatography (ethyl acetate:
n-hexane=1:1) to give pale yellow crystals (82.3 mg, 79%). The
crystals were recrystallized from methylene chloride-diisopropyl
ether to give the desired compound as colorless needles (50.5 mg,
48%).
Example 13
Synthesis of Compound (I-120)
[0342] 64
[0343] Ethyl 4-amino-1-piperidinecarboxylate (300 mg) and
triethylamine (258 mg) were dissolved in 5 ml of dichloromethane.
To the mixture, 2 ml of solution of t-butylsulfinyl chloride (222
mg) in dichloromethane was added and the mixture was stirred at
room temperature for 4 hours. The solution was partitioned into an
aqueous solution of potassium hydrogen sulfate and ethyl acetate.
The organic layer was washed with brine and dried over magnesium
sulfate anhydride. The solvent was removed under reduced pressure
and the residue was purified by silica gel chromatography to give
378 mg of 4-t-butylsulfiny amino-1-ethoxycarbonyl piperidine.
65
[0344] In a mixture of 5 ml of 2-propanol and 5 ml of water, 378 mg
of 4-t-butylsulfinylamino-1-ethoxycarbonyl piperidine was suspended
and 1.77 g of barium hydroxide was added. The mixture was refluxed
with stirring and heating for 4 hours. The mixture was diluted with
methanol and the insoluble material was filtered off. The solvent
was removed under reduced pressure to give
4-t-butylsulfinylaminopiperidine. Without purification, the
obtained material was dissolved in 5 ml of THF, and 984 mg of
N-phenoxycarbonyl-4-butyl aniline and 236 mg of diisopropyl
ethylamine were added, followed by stirring at room temperature
overnight. An aqueous solution of potassium hydrogen sulfate was
added to the mixture and the mixture was extracted with ethyl
acetate. The organic layer was washed with brine and dried over
magnesium sulfate anhydride. The solvent was removed under reduced
pressure and the residue was purified by silica gel chromatography
to give 291 mg of 4-t-butylsulfinylaminopiperidine-1-carboxlic
acid(4-t-butylphenyl)amide.
[0345] .sup.1H-NMR (CDCl.sub.3) .delta. ppm:0.89(t, 3H, J=7.3 Hz),
1.19(s, 9H), 1.25-1.38(m, 4H), 1.40-1.60(m, 4H), 1.89-2.03(m, 3H),
2.52(t, 2H, J=7.7 Hz), 2.89-3.04(m, 2H), 3.14(d, 1H, J=5.2 Hz),
3.37(m, 1H), 3.96(m, 2H), 6.67(s, 1H), 7.05(d, 2H, J=8.5 Hz),
7.22(d, 2H, J=8.5 Hz). 66
[0346] In a mixture of 2 ml of methanol and 2 ml of methylene
chloride, 291 mg of 4-t-butylsulfinyl aminopiperidine-1-carboxlic
acid(4-t-butylphenyl)amide was dissolved. To the mixture, 570 mg of
80%-MMPP (magnesium monoperoxyphthalate hexahydrate) was added and
the mixture was stirred at room temperature for 2 hours. The
solution was diluted with water and extracted with ethyl acetate.
The organic layer was washed with brine and dried over magnesium
sulfate anhydride. The solvent was removed under reduced pressure
and the residue was purified by silica gel chromatography to give
130 mg of 4-t-butylsulfonylaminopipe- ridine-1-carboxylic
acid(4-butylphenyl)amide (I-120).
[0347] Other Compounds (I) are synthesized by the similar methods.
The structures and physical properties are shown below.
6768697071727374757677787980818283848586878889909192939495969798991001011-
02103104105106107108109110111112113114115116117118119120121122123124125126-
12712812913013113213313413513613713813914014114214314414514614714814915015-
1152153154155156157158159160161162163164165
166167168169170171172173174175-
17617717817918018118218318418518618718818919019119219319419519619719819920-
02012022032042052062072082092102112122132142152162172182192202212222232242-
25226227228229230231232233234235236237238239240241242243
[0348] I-2
[0349] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.94 (t, 3H, J=7.5 Hz),
1.34-1.44 (m, 2H), 1.40 (d, 6H, J=6.6 Hz). 1.59-1.68 (m, 2H), 2.69
(t, 2H, J=7.8 Hz), 3.24-3.35 (m, 1H), 6.49 (s, 1H), 7.23-7.32 (m,
4H), 7.6 (d, 2H, J=8.7 Hz), 7.79 (d, 2H, J=8.1 Hz), 7.85 (s,
1H).
[0350] I-3
[0351] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.2 Hz),
1.30-1.39 (m, 2H), 1.37 (d, 6H, J=6.9 Hz), 1.57 (quint, 2H, J=7.5
Hz), 1.96 (quint, 2H, J=6.6 Hz), 2.49 (t, 2H, J=6.6 Hz), 2.57 (t,
2H, J=7.8 Hz), 3.16-3.26 (m, 3H), 4.62 (brs, 1H), 7.12 (d, 2H,
J=8.1 Hz), 7.43 (d, 2H, J=8.4 Hz), 7.64 (s, 1H).
[0352] I-4
[0353] .sup.1H-NMR (CD.sub.3OD) .delta.ppm: 0.92 (t, 3H, J=6.9 Hz),
1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.3 Hz), 1.53-1.63 (m, 2H), 2.58
(t, 2H, J=7.8 Hz), 3.33-3.43 (m, 1H), 6.27-6.29 (m, 1H), 7.14-7.16
(m, 3H), 7.50 (d, 2H, J=8.4 Hz), 7.90 (s, 1H).
[0354] I-5
[0355] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.2 Hz),
1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.9 Hz), 1.53-1.63 (m, 2H), 2.59
(t, 2H, J=7.8 Hz). 3.35-3.44 (m, 1H), 7.15 (d, 2H, J=8.7 Hz), 7.38
(s, 1H), 7.45 (d, 2H, J=8.7 Hz), 7.57 (s, 1H).
[0356] I-6
[0357] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.29-1.39 (m, 2H), 1.37 (d, 6H, J=6.9 Hz), 1.55 (quint, 2H, J=7.5
Hz), 2.55 (t, 2H, J=5.1 Hz), 3.18-3.27 (m, 1H), 3.92 (d, 2H, J=6.0
Hz), 5.51 (t, 1H, J=5.7 Hz), 7.10 (d, 2H, J=8.4 Hz), 7.39 (d, 2H,
J=8.4 Hz), 8.23 (s, 1H)
[0358] I-7
[0359] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.28-1.38 (m, 2H), 1.37 (d, 6H, J=6.9 Hz), 1.51-1.67 (m, 4H),
1.78-1.88 (m, 2H), 2.39 (t, 2H, J=7.2 Hz), 2.57 (t, 2H, J=7.5 Hz),
3.12-3.22 (m, 3H), 4.30-4.37 (m, 1H), 7.12 (d, 2H, J=8.4 Hz),
7.36-7.42 (m, 3H).
[0360] I-8
[0361] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t 3H, J=7.5 Hz),
1.21-1.47 (m, 4H), 1.35 (d, 6H, J=6.6 Hz), 1.51-1.63 (m, 4H),
1.67-1.77 (m, 2H), 2.34 (t 2H, J=7.5 Hz), 2.55 (t, 2H, J=7.8 Hz),
3.08-3.17 (m, 3H), 4.71 (t, 1H, J=6.0 Hz), 7.09 (d, 2H, J=8.1 Hz),
7.43 (d, 2H, J=8.4 Hz), 7.74 (s, 1H).
[0362] I-9
[0363] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.29-1.39 (m, 21), 1.35 (d, 6H, J=6.9 Hz), 1.50-1.60 (m, 2H), 2.54
(t, 2H, J=7.8 Hz), 2.64 (t, 2H, J=5.7 Hz), 3.14-3.23 (m, 1H),
3.41-3.47 (m, 2H), 5.29 (t, 1H, J=6.3 Hz), 7.10 (d, 2H, J=8.4Hz),
7.39 (d, 2H, J=8.4 Hz), 7.91 (s, 1H).
[0364] I-10
[0365] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.22 (s, 9H), 1.30-1.37 (m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86 (m,
2H), 2.31-2.40 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.15-3.26 (m, 3H),
7.11 (t, 2H, J=8.7 Hz), 7.42 (d, 2H, J=8.1 Hz), 7.54 (s, 1H).
[0366] I-11
[0367] mp: 128-129.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.91 (t 3H, J=7.5 Hz), 1.29-1.39 (m, 2H), 1.39 (s, 9H), 1.51-1.68
(m, 4H). 1.76-1.84 (m, 2H), 2.37 (t, 2H, J=7.5 Hz), 2.56 (t, 2H,
J=7.8 Hz), 3.19-3.26 (m, 2H), 4.20 (t, 1H, J=5.7 Hz), 7.11 (d, 211,
J=8.1. Hz), 7.42 (d, 2H, J=8.7 Hz), 7.46 (s, 1H).
[0368] I-12
[0369] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.28-1.37 (m, 2H), 1.47-1.68 (m, 6H), 2.23 (t, 2H, J=7.2 Hz), 2.56
(t, 2H, J=7.5 Hz), 2.90-2.97 (2H), 5.10 (brs, 1H), 7.(d, 2H, J=8.4
Hz), 7.36 (d, 2H, J=8.1 Hz), 7.50-7.68 (m, 3H), 7.93 (d, 1H, J=8.1
Hz), 8.06 (d, 1H, J=8.4 Hz), 8.24 (d, 1H, J=7.5 Hz), 8.66 (d, 1H,
J=8.7 Hz).
[0370] I-13
[0371] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.28-1.40 (m, 2H), 1.45-1.73 (m, 6H), 2.23 (t, 2H, J=7.5 Hz), 2.56
(t, 2H, J=7.8 Hz), 2.88 (s, 6H), 2.88-2.95 (m, 2H), 5.04 (brs, 1H),
7.10(d, 2H, J=8.1 Hz), 7.17 (d, 1H, J=7.2 Hz), 7.37 (cl, 2H, J=8.4
Hz), 7.48-7.54 (m, 2H), 8.23 (d, H, J=7.2 Hz), 8.30 (d, 1H, J=8.7
Hz), 8.53 (d, 1H, J=8.4Hz).
[0372] I-14
[0373] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.30-1.43 (m, 6H), 1.36 (d, 6H, J=6.6 Hz), 1.51-1.62 (m, 4H),
1.67-1.78 (m, 2H), 2.34 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz),
3.09-3.20 (m, 3H), 4.34 (brs, 1H), 7.10 (d, 2H, J=8.4 Hz),
7.41-7.44 (m, 3H).
[0374] I-15
[0375] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.23 (s, 9H), 1.27-1.80 (m, 12H), 2.30-2.38 (m, 2H), 2.56 (t, 2H,
J=7.5 Hz), 3.15 (brs, 2H), 7.11 (d, 2H, J=7.8 Hz), 7.43 (d, 2H,
J=7.8 Hz), 7.59 (s, 1H).
[0376] I-16
[0377] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1..29-1.44 (m, 6H), 1.39 (s, 9H), 1.51-1.61 (m. 4H), 1.68-1.78 (m,
2H), 2.35 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=8.1 Hz), 3.15-3.21 (m,
2H). 4.14-4.23 (m, 1H), 7.11 (d, 2H, J=7.8 Hz), 7.36-7.44 (m,
3H).
[0378] I-19
[0379] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.5 Hz),
1.21 (s, 9H), 1.30-1.40 (m, 2H), 1.55-1.72 (m, 6H), 2.64 (t, 2H,
J=7.8 Hz), 3.08-3.33 (m, 3H), 3.42-3.50 (m, 2H), 6.39 (s, 1H), 7.22
(d, 2H, J=8.4 Hz), 7.69 (d, 2H, J=8.1 Hz).
[0380] I-20
[0381] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.2 Hz),
1.31-1.39 (m, 2H), 1.39 (s, 9H), 1.55-1.72 (m, 6H), 2.64 (t, 2H,
J=7.8 Hz), 3.24 (quart, 2H, J=6.6 Hz), 3.48 (quart, 2H, J=6.6 Hz),
4.21 (t, 1H, J=6.3 Hz), 6.29 (s, 1H), 7.22 (d, 2H, J=7.8 Hz), 7.67
(d, 2H, J=8.1 Hz).
[0382] I-21
[0383] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.23 (s, 9H), 1.30-1.42 (m, 2H), 1.50-2.02 (m, 10H), 2.30-2.42 (m,
1H), 2.57 (t, 2H, J=8.1 Hz), 3.10 (brs, 1H), 3.57 (brs, 1H), 7.12
(d, 2H, J=8.4 Hz), 7.41 (d, 2H, J=7.8 Hz).
[0384] I-22
[0385] mp: 78-79.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.91 (t, 3H, J 7.2 Hz), 1.30-1.40 (m, 2H), 1.40 (s, 9H), 1.50-1.65
(m, 4H), 1.70-1.98 (m, 8H), 2.30-2.40 (m, 1H), 2.57 (t, 2H, J=7.5
Hz), 3.58-3.70 (m, 1H), 4.16 (d, 1H, J=9.3 Hz), 7.11-7.15 (m, 3H),
7.40 (d, 2H, J=8.1 Hz).
[0386] I-23
[0387] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.21 (s, 9H), 1.21-1.41 (m, 4H), 1.51-1.64 (m, 4H), 1.86-2.01 (m,
4H), 2.12-2.25 (m, 1H), 2.56 (t, 2H, J=7.5 Hz), 2.87-2.96 (m, 1H),
3.00-3.12 (m, 1H), 3.23-3.34 (m, 1H), 3.67-3.75 (m, 1H), 7.11 (d,
2H, J=8.1 Hz), 7.40 (d, 2H, J=8.4 Hz).
[0388] I-24
[0389] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.25-1.37 (m, 2H), 1.40 (s, 9H), 1.48-1.65 (m, 6H), 1.90 (d, 2H,
J=11.7 Hz), 2.02(d, 2H, J=11.7Hz), 2.12-2.24 (m, 1H), 2.56 (t, 2H,
J=7.5 Hz), 3.04 (t, 2H, J=6.3 Hz), 4.31 (t, 1H, J=5.7 Hz), 7.11 (d,
2H, J=8.1 Hz), 7.42 (d, 2H, J=8.4 Hz).
[0390] I-25
[0391] mp: 232-233.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.91 (t, 3H, J=7.5 Hz), 1.23-1.40 (m, 4H), 1.40 (s, 9H), 1.51-1.76
(m, 4H), 2.01-2.26 (m, 5H), 2.56 (t, 2H, J=7.5 Hz), 3.22-3.38 (m,
1H), 3.79 (d, 1H, J=9.3 Hz), 7.11 (d, 2H, J=8.7 Hz), 7.17 (s, 1H),
7.10 (d, 2H, J=8.4 Hz).
[0392] I-26
[0393] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.22 (s, 9H), 1.28-1.40 (m, 2H), 1.52-1.62 (m. 2H), 1.85-1.96 (m,
1H), 2.00-2.14 (m 1H), 2.38-2.53 (m, 2H), 2.56 (t, 2H, J=7.5 Hz),
3.22-3.37 (m, 3H), 7.11 (d, 2H, J=8.4 Hz), 7.45 (d, 2H, J=8.4 Hz),
8.19 (s, 1H).
[0394] I-27
[0395] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.30-1.40 (m, 2H), 1.40 (s, 9H), 1.52-1.61 (m, 2H), 1.95 (quint,
2H, J=6.3 Hz), 2.50 (t: 21H J=6.9 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.31
(quart, 2H, J=6.0 Hz), 4.30-4.36 (m, 1H), 7.12 (d, 2H, J=8.4 Hz),
7.43 (d, 2H, J=8.4 Hz), 7.65 (s, 1H).
[0396] I-28
[0397] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2 Hz),
1.21 (s, 9H), 1.30-1.62 (m, 8H), 2.08 (d, 4H, J=11.1 Hz), 2.56 (t,
2H, J=7.8 Hz), 3.04 (d, 1H, J=4.8 Hz), 3.20-3.30 (m, 1H), 4.65-4.76
(m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.7 Hz), 7.26 (d, 2H, J=8.1
Hz).
[0398] I-29
[0399] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.2Hz),
1.23-1.62 (m, 8H), 1.40 (s, 9H), 2.12 (d, 4H, J=14.4 Hz), 2.56 (t,
2H, J=7.8 Hz), 3.28-3.40 (m, 1H), 3.90 (s, 1H), 4.60-4.73 (m, 1H),
6.57 (s, 1H), 7.10 (d, 2H, J=8.4 Hz), 7.25 (d, 2H, J=8.4Hz).
[0400] I-30
[0401] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91 (t, 3H, J=7.5 Hz),
1.26-1.39 (m, 2H), 1.51.-1.64 (m, 4H), 1.72-1.81 (m, 2H), 2.34 (t,
2H, J=6.9 Hz), 2.56 (t, 2H, J=7.8 Hz), 2.95-3.01 (m, 2H), 4.84 (t,
11H, J=5.7 Hz), 6.99-7.12 (m, 6H), 7.19-7.24 (m, 1H), 7.30 (s, 1H),
7.38-7.43 (m, 4H), 7.79 (d, 2H. J=8.7 Hz).
[0402] I-31
[0403] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.5 Hz),
1.21 (s, 9H), 1.28-1.62 (m, 8H), 2.07-2.14 (m, 4H), 2.64 (t, 2H,
J=7.8 Hz), 3.11 (d, 1H, J=5.1 Hz), 3.20 (brs, 1H), 3.90-4.04 (m,
1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H, J=8.1 Hz), 7.67 (t, 2H, J=8.4
Hz).
[0404] I-32
[0405] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.2 Hz),
1.27-1.65 (m, 8H), 1.40 (s, 9H), 2.10-2.23 (m, 4H), 2.65 (t, 2H,
J=7.5 Hz), 3.23-3.35 (m, 1H), 3.49 (s, 1H), 3.88-4.02 (m, 1H),
5.84-5.92 (m, 1H), 7.13 (t, 2H, J=8.4 Hz): 7.65 (d, 2H, J=8.1
Hz).
[0406] I-33
[0407] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.94 (t, 3H, J=7.2 Hz),
1.30-1.42 (m, 2H) 1.32 (s, 9H), 1.57-1.66 (m, 2H), 2.67 (t, 2H,
J=7.8 Hz), 5.61 (s, 1H), 6.93 (d, 2H, J=8.7 Hz), 7.25 (d, 2H, J=8.4
Hz), 7.49 (d, 2H, J=9.0 Hz), 7.80 (d, 2H, J=8.1 Hz), 8.22 (s,
1H).
[0408] I-34
[0409] .sup.1H-NMR (CD.sub.3OD) .delta.ppm: 0.95 (t, 3H, J=7.5 Hz),
1.35 (s, 9H), 1.35-1.44 (m, 2H), 1.57-1.69 (m, 2H), 2.69 (t, 2H,
J=7.5 Hz), 7.28-7.33 (m, 4H), 7.56 (d, 2H, J=9.0 Hz), 7.83 (d, 2H,
J=8.4 Hz).
[0410] I-36
[0411] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.5 Hz),
1.31-1.70 (m, 11H), 1.39 (s, 9H), 1.75-1.85 (m, 1H), 2.65 (t, 2H,
J=8.1 Hz), 3.13 (t 2H, J=6.6Hz), 3.40 (t, 2H, J=7.2 Hz), 4.10 (t,
1H, J=5.7 Hz), 6.21 (t, 1H, J=5.7 Hz), 7.23 (d, 2H, J=8.1 Hz), 7.67
(d, 2H, J=8.4 Hz).
[0412] I-37
[0413] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.92 (t, 3H, J=7.5 Hz),
0.95-1.10 (m, 2H), 1.31-1.40 (m, 2H), 1.39 (s, 9H), 1.55-1.63 (m,
4H), 1.80-1.92 (m, 4H), 2.65 (t, 2H, J=7.8 Hz), 3.03 (t, 2H, J=6.6
Hz), 3.31 (t,2H, J=6.6 Hz), 4.06 (t, 1H, J=6.0 Hz), 6.22 (t, 1H,
J=6.0 Hz), 7.23 (d, 2H, J=8.4 Hz), 7.67 (d, 2H, J=8.1 Hz).
[0414] I-39
[0415] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.13 (t 3H, J=7.2 Hz),
1.39 (s, 9H), 1.69-1.97 (m, 8H), 2.27-2.38 (m, 1H), 3.29-3.35 (m,
4H), 3.60-3.70 (m, 1H), 4.52 (d, 1H, J=9.3 Hz), 6.64 (d, 2H, J=8.4
Hz), 7.22 (s, 1H), 7.31 (d, 21, J=9.0 Hz).
[0416] I-40
[0417] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.38 (s, 9H), 1.68-1.96
(m, 8H), 2.30-2.40 (m, 1H), 3.11 (t, 4H, J=4.8 Hz), 3.60-3.72 (m,
1H), 3.86 (t, 4H, J=4.8 Hz), 4.51 brs, 1H), 6.89 (d, 2H, J=9.0 Hz),
7.42 (d, 2H, J=8.7 Hz).
[0418] I-41
[0419] mp: >278.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.18-1.40 (m, 2H), 1.40 (s, 9H), 1.62-1.75 (m, 2H),
2.01-2.27 (m, 5H), 3.10-3.13 (m. 4H), 3.22-3.38 (m, 1H), 3.72 (d,
1H, J=9.3Hz), 3.85-3.88 (m, 4H), 6.87 (d, 2H, J=9.0 Hz), 7.10 (s,
1H), 7.40 (d, 2H, J=9.0 Hz).
[0420] I-42
[0421] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.40 (s, 9H), 1.61-1.97
(m, 8H), 2.16 (s, 3H), 2.33-2.43 (m, 1H), 3.60-3.70 (m, 1H), 4.66
(brs, 1H), 7.12 (d, 1H, J=8.7 Hz), 7.46-7.50 (m, 1H), 7.62 (s, H),
7.75-7.78 (m, 1H), 7.86-7.91 (m, 2H).
[0422] I-43
[0423] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.40 (s, 9H), 1.62-2.00
(m, 8H), 1.87 (s, 3H), 2.36-2.47 (m, 1H), 3.24 (s, 3H), 3.64-3.74
(m, 1H), 4.87 (brs, 1H), 7.13 (d, 2H, J=9.0 Hz), 7.64 (d, 2H, J=8.4
Hz), 7.81 (s, H).
[0424] I-44
[0425] mp: 235-236.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.13 (t, 6H, J=6.9 Hz), 1.18-1.33 (m, 2H), 1.40 (s, 9H), 1.60-1.77
(m, 2H), 2.00-2.26 (m, 5H), 3.28-3.35 (m, 4H), 3.73 (d, 1H, J=9.3
Hz), 6.60-6.70 (m, 2H), 7.03 (brs, 1H), 7.31 (d, 2H, J=7.8 Hz).
[0426] I-45
[0427] mp: >268.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.20-1.34 (m, 2H), 1.40 (s, 9H), 1.56-1.76 (m,8H),
2.00-2.26 (m, 5H), 3.06-3.14 (m, 4H), 3.24-3.36 (m, 1H), 3.72 (d,
1H, J=9.3 Hz), 6.90 (d, 2H, J=8.7 Hz), 7.09 (s, 1H), 7.36 (d, 2H.
J=8.7 Hz).
[0428] I-46
[0429] mp : >272.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.28 (s, 9H), 1.31-1.59 (m. 7H), 1.87-2.00 (m, 4H),
2.23-2.34 (m, 1H), 3.00-3.16 (m, 1H), 4.35-4.45 (m, 2H), 6.81 (d,
1H, J=9.0 Hz), 7.16 (t, 1H, J=7.2 Hz), 7.43 (t, 1H, J=8.4 Hz),
7.52-7.58 (m, 3H), 8.04 (d, 1H, J=7.8 Hz), 8.43 (s, 1H).
[0430] I-47
[0431] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.20-1.36 (m, 2H), 1.40
(s, 9H), 1.62-1.77 (m, 2H), 1.98-2.32 (m, 5H), 3.31-3.40 (m, 1H),
3.62 (d, 1H, J=9.0 Hz), 7.08 (s, 1H), 7.29 (d, 2H, J=9.0 Hz), 7.61
(d, 2H, J=9.0 Hz).
[0432] I-48
[0433] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.22-1.36(m 2H),
1.40(s, 9H), 1.62-1.77(m, 2H), 2.00-2.31 (m, 5H), 3.24-3.40 (m,
1H), 3.62 (d, 1H, J=10.2 Hz), 7.01 (t, 2H, J=8.7 Hz), 7.09 (s, 1H),
7.42-7.50 (m, 2H).
[0434] I-49
[0435] mp: 270.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.61-1.77 (m, 2H),
1.95-2.30 (m, 9H), 3.17-3.38 (m, 5H), 3.67 (d, 1H, J=9.3 Hz), 6.50
(d, 2H, J=9.0 Hz), 6.97 (s, 1H), 7.30 (d, 2H, J=9.0 Hz).
[0436] I-50
[0437] mp: 252-253.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.21-1.37 (m, 2H), 1.40 (s, 9H), 1.62-1.78 (m, 2H), 1.98-2.32 (m,
5H), 3.26-3.40 (m, 1H), 3.68 (d, 1H, J=9.6 Hz), 6.94-7.02 (m, 4H),
7.08 (t, 1H, J=7.5 Hz), 7.13 (s, 1H), 7.31 (t, 2H, J=7.5 Hz), 7.46
(d, 2H, J=9.0 Hz).
[0438] I-51
[0439] mp: 278-279.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.02 (d, 6H, J=6.9 Hz), 1.35 (s, 9H), 1.39-1.71 (m, 6H), 1.90-2.09
(m, 2H), 3.16-3.30 (m, 1H), 3.46 (d, 1H, J=9.0 Hz), 4.92-5.01 (m,
1H), 6.91-6.95 (m, 2H), 7.00-7.07 (m, 3H), 7.13-7.16 (m, 2H),
7.30-7.36 (m, 2H).
[0440] I-52
[0441] mp : 276-277.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.30 (m,
5H), 2.36 (s, 3H), 2.58 (t, 4H, J=4.5 Hz), 3.17 (t, , J=4.5 Hz),
3.21-3.40 (m, 1H), 3.64 (d, 1H, J=9.0 Hz), 6.88 (d, 2H, J=9.0 Hz),
7.01 (s, 1H), 7.37 (d, 2H, J=9.0 Hz).
[0442] I-53
[0443] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H), 1.73-1.88 (m, 2H),
1.89-2.01 (m, 2H), 2.13-2.25 (m, 1H), 2.98-3.12 (m, 1H), 3.15-3.:31
(m, 8H), 6.76-6.84 (m, 2H), 6.93 (d, 2H, J=9.0 Hz), 6.99 (d, 2H,
J=8.1 Hz), 7.24 (d, 2H, J=8.1 Hz), 7.46 (d, 2H, J=9.0 Hz), 9.60 (s,
1H).
[0444] I-54
[0445] mp: >215.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-2.00 (m, 18H), 2.14-2.26 (m, 1H),
2.53-2.84 (m, 4H), 2.86-3.30 (m, 2H), 3.46-3.54 (m, 1H), 3.62-3.74
(m, 2H), 6.78 (d, 1H, J=8.7 Hz), 6.87 (d, 2H, J=7.8 Hz), 7.42 (d,
2H, J=8.7 Hz), 9.58 (s, 1H).
[0446] I-55
[0447] mp: >290.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1.60-1.76 (m, 2H),
2.02-2,27 (m, 5H), 3.20 (t, 4H, J=5.4 Hz), 3.21-3.32 (m, 1H), 3.67
(d, 1H, J=9.3 Hz), 3.98 (t, 4H, J=4.8 Hz), 6.52 (t, 1H, J=4.8 Hz),
6.93 (d, 2H, J=8.4 Hz), 7.06 (s, 1H), 7.41 (d, 2H, J=8.7 Hz), 8.33
(d, 2H, J=4.8 Hz).
[0448] I-56
[0449] mp: >232.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.48 (m, 4H), 1.80-1.99 (m, 4H),
2.14-2.25 (m, 1H), 3.04-3.24 (m, 8H), 3.68 (s, 3H), 3.76 (s, 3H),
6.44-6.47 (m, 1H), 6.76-6.84 (m, 2H), 6.92 (d, 2H, J=8.4 Hz), 7.46
(d, 2H, J=8.4 Hz), 9.61 (s, 1H).
[0450] I-57
[0451] mp: 284-285.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.27 (t, 3H, J=7.2 Hz), 1.40 (s, 9H), 1.61-2.24 (m,
9H), 2.35-2.49 (m, 1H), 2.76 (t, 2H, J=10.2 Hz), 3.04-3.15 (m, 2H),
3.20-3.36 (m, 1H), 3.55-3.59 (m, 2H), 3.87 (d, 1H, J=9.6 Hz),
4.12-4.19 (m, 2H), 6.90 (d, 2H, J=8.7 Hz), 2.79 (s, 1H), 7.40 (d,
2H, J=8.7 Hz).
[0452] I-58
[0453] mp: >299.degree. C. (dec.). .sup.1H-NMR (CDCl3)
.delta.ppm: 1.26-1.33 (m, 2H), 1.40 (s, 9H), 1.56-2.42 (m, 19H),
2.73-2.81 (m, 4H), 3.16-3.26 (m, 4H), 3.64 (d, 1H, J 9.6 Hz), 6.87
(d, 2H, J=8.7 Hz), 7.04 (s, 1H), 7.37 (d, 2H, J=9.0 Hz).
[0454] I-59
[0455] mp: >270.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.26-1.47 (m, 2H), 1.47 (s, 9H), 1.60-1.80 (m, 4H),
2.01-2.32 (m, 5H), 3.28-3.40 (m, 3H), 3.62-3.74 (m, 3H), 5.74-5.96
(m, 2H), 6.92 (d, 2H, J=8.7 Hz), 7.13 (s, 1H), 7.39 (d, 2H, J=9.0
Hz).
[0456] I-60
[0457] mp: 247-250.degree. C. (dec.). .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.20-1.37(m, 2H), 1.40(s, 9H), 1.60-1.78(m, 2H),
1.98-2.33 (m, 5H), 2.93-3.03 (m, 2H), 3.22-3.40 (m, 1H), 3.52 (t,
2H, J=6.0 Hz), 3.62 (d, 1H, J=8.4 Hz), 4.36 (s, 2H), 6.93 (d, 2H,
J=8.7 Hz), 7.00 (s, 1H), 7.11-7.22 (m, 4H),7.39 (d, 2H, J=8.7
Hz).
[0458] I-61
[0459] mp: 280-281.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.21-1.38 (m, 2H), 1.41 (s, 9H), 1.64-1.80 (m, 2H), 2.02-2.33 (m,
5H), 3.24-3.40 (m, 1H), 3.61 (d, 1H, J=9.0 Hz), 6.33 (t, 2H. J=2.1
Hz), 7.04 (t, 2H, J=2.1 Hz), 7.14 (s, 1H), 7.34 (d, 2H, J=9.0 Hz),
7.56 (d, 2H, J=9.0 Hz).
[0460] I-62
[0461] mp: 260-262.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.39 (m, 2H), 1.41 (s, 9H), 1.64-1.82 (m, 2H), 2.02-2.35 (m,
5H): 3.24-3.40 (m, 1H), 3.62 (d, 1H, J=9.6 Hz), 7.31 (d, 2H, J=9.0
Hz), 7.51 (s, 1H), 7.69 (d, 2H, J=9.0 Hz).
[0462] I-63
[0463] mp: 248.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.20-1.38 (m, 2H), 1.40 (s, 9H), 1.61-1.78 (m, 2H), 1.98-2.32 (m,
5H), 3.22-3.45 (m, 1H), 3.64 (d, 1H, J=9.3 Hz), 7.11 (s, 1H),
7.37-7.46 (m, 4H).
[0464] I-64
[0465] mp: 272-275.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.20-1.53 (m , 4H) 1.27 (s, 9H), 1.75-1.88 (m, 2H),
1.88-2.00 (m, 2H), 2.11-2.24 (m, 1H), 2.96-3.12 (m, 1H), 5.96 (s,
2H), 6.77 (d, 1H, J=8.7 Hz), 6.82 (d, 1H, J=8.4 Hz), 6.95 (dd, 1H,
J=1.8, 8.4 Hz), 7.29 (d, 1H, J=1.8 Hz), 9.70 (s, 1H).
[0466] I-65
[0467] mp: 293-296.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.20-1.70 (m, 10H), 1.27 (s, 9H), 1.79-2.038 (m, 4H),
2.18-2.33 (m, 1H), 2.98-3.30 (m, 5H), 6.79 (d, 1H, J=9.0 Hz), 6.97
(d, 2H, J=8.1 Hz), 7.43-7.57 (m, 4H), 7.62 (d, 2H, J=8.1 Hz), 9.82
(s, 1H).
[0468] I-66
[0469] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.53 (m, 4H), 1.86-1.99 (m, 4H),
2.22-2.34 (m, 1H), 2.39 (s, 3H), 3.00-3.14 (m, 1H), 6.25 (s, 1H),
6.79 (d, 1H, J=9.0 Hz), 7.47-7.50 (m, 1H), 7.69-7.76 (m, 1H), 10.27
(s, 1H).
[0470] I-67
[0471] mp: 248-249.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H), 1.77-1.90 (m, 2H),
1.90-2.02 (m, 2H), 2.02 (s, 3H), 2.17-2.32 (m, 1H), 2.96-3.13 (m,
1H), 6.78 (d, 1H, J=8.7 Hz), 7.12-7.30 (m, 3H), 7.89 (s, 1H), 9.79
(s, 1H), 9.88 (s, 1H).
[0472] I-68
[0473] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H). 1.77-1.89 (m, 2H),
1.89-2.03 (m, 2H). 2.00 (s, 3H), 2.14-2.28 (m, 1H), 2.95-3.13 (m,
1H), 6.78 (d, 1H, J=8.7 Hz), 7.40-7.54 (m, 4H), 9.72 (s, 1H), 9.83
(s, 1H).
[0474] I-69
[0475] mp: 199-201.degree. C. .sup.1H-NMR ((DMSO-d.sub.6)
.delta.ppm: 1.21-1.53 (m, 4H), 1.27 (s, 9H), 1.76-1.89 (m, 2H),
1.89-2.02 (m, 2H), 2.13-2.30 (m, 1H), 2.85 (s, 6H), 2.94-3.14 (m,
1H), 6.40 (dd, 1H, J=2.4, 8.4 Hz), 6.78 (d, 1H, J=8.7 Hz), 6.90 (d,
1H, J=8.4 Hz), 7.05 (t, 2H, J=8.4 Hz), 9.60 (s, 1H).
[0476] I-70
[0477] mp: 227-230.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H), 1.72-1.87 (m, 2H),
1.87-2.01 (m, 2H), 2.12-2.29 (m, 1H), 2.96-3.12 (m, 1H), 5.00 (s,
2H), 6.22 (d, 1H, J=7.5 Hz), 6.66 (d, 1H, J=7.5 Hz), 6.78 (d, 1H,
J=9.0 Hz), 6.86 (s 1H, J=7.5 Hz), 6.89-6.95 (m, 1H), 9.46 (s,
1H).
[0478] I-71
[0479] mp: 270-272.degree. C. 1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.22-1.52 (m, 4H), 1.26 (s, 9H), 1.73-1.86 ( s, 2H), 1.88-2.00 (m,
2H), 2.08-2.22 (m, 1H), 2.95-3.11 (m, 1H), 4.80 (s, 2H), 6.47 (d,
2H, J=8.4 Hz), 6.77 (d, 1H, J=8.4 Hz), 7.20 (d, 2H, J=8.4 Hz), 9.35
(s, 1H).
[0480] I-72
[0481] mp: 262-263.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.17-1.42 (m, 2H), 1.40 (s, 9H), 1.60-1.78
(m, 2H), 1.98-2.43 (m, 7H), 3.20-3.43 (m, 3H), 3.67 (d, 1H, J=9.6
Hz), 3.74-3.86 (m, 2H), 6.86 (d, 2H, J=9.0 Hz), 7.04 (s, 1H), 7.38
(d, 2H, J=9.0 Hz).
[0482] I-73
[0483] mp: 218-219.degree. C. .sup.1H-NMR (CD.sub.3OD) .delta.ppm:
1.36 (s, 9H), 1.36-1.69 (m, 4H), 1.45 (s, 9H), 1.88-2.02 (m, 3H),
2.06-2.30 (m, 4H), 3.05-3.44 (m, 3H), 3.46-3.56 (m, 1H), 4.16-4.26
(m, 1H), 6.51 (d, 2H, J=9.0 Hz), 7.30 (d, 2H, J=8.7 Hz).
[0484] I-74
[0485] mp: 295-296.degree. C. (dec.). .sup.1H-NMR (CD.sub.3OD)
.delta.ppm: 1.36 (s, 9H), 1.36-1.67 (m, 4H), 1.92-2.13 (m, 4H),
2.26-2.40 (m, 2H), 2.62-2.75 (m, 1H), 3.16-3.25 (m, 1H), 3.58-3.98
(m, 4H), 4.16-4.25 (m, 1H), 7.20-7.30 (m, 2H), 7.62 (d, 2H, J=9.0
Hz).
[0486] I-75
[0487] mp: 250-251.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.23-1.55 (m, 4H), 1.27 (s, 9H), 1.78-1.90 (m, 2H),
1.90-2.02 (m, 2H), 2.15-2.28 (m, 1H), 2.98-3.14 (m, 1H), 3.06 (t,
2H, J=8.4 Hz), 3.87 (t, 2H, J=8.4 Hz), 6.67 (dd, 1H, J=1.5, 7.2
Hz), 6.80 (d, 1H, J=8.4 Hz), 6.94-7.05 (m, 2H), 7.12-7.19 (m, 1H),
7.16 (d, 2H, J=9.3 Hz), 7.57 (d. 2H, J=9.3 Hz), 9.73 (s, 1H).
[0488] I-76
[0489] mp: 265-266.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.23-1.58 (m, 4H), 1.28 (s, 9H), 1.83-2.04 (m, 4H),
2.20-2.36 (m, 1H), 2.97-3.16 (m, 1H), 6.67 (d, 1H, J=3.0 Hz), 6.82
(d, 1H, J=8.4 Hz), 7.07-7.22 (m, 2H), 7.47-7.53 (m, 1H), 7.50 (d,
2H, J=9.0 Hz), 7.58 (d, 1H, J=3.0 Hz), 7.64 (d, 1H, J=7.5 Hz), 7.79
(d, 2H, J=9.0 Hz), 10.02 (s, 1H).
[0490] I-77
[0491] mp: 281.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.21-1.56 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.18-2.31 (m,
1H), 2.97-3.14 (m, 1H), 6.51 (dd, 1H, J=2.1, 2.7 Hz), 6.81 (d, 1H,
J=9.0 Hz), 7.67-7.78 (m,5H), 8.41 (d, 1H, J=2.1 Hz), 9.96 (s,
1H).
[0492] I-78
[0493] mp: >300.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.52 (m, 4H), 1.74-2.04 (m, 7H),
2.10-2.25 (m, 2H), 2.96-3.20 (m, 2H), 3.48-3.58 (m, 1H), 3.75-3.84
(m, 1H), 6.39 (d, 2H, J=8.4 Hz),
[0494] I-79
[0495] mp: 248-2.50.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.54 (m, 4H), 1.85-1.99 (m, 4H),
2.24-2.33 (m, 1H), 3.00-3.14 (m, 1H), 6.82 (d, 1H, J=8.7 Hz), 7.77
(d, 2H, J=8.4 Hz), 8.07 (d, 2H, J=8.4 Hz).
[0496] I-80
[0497] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.22-1.58 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H),
2.18-2.32 (m, 1H), 2.98-3.14 (m, 1H), 6.80 (d, 1H, J=8.7 Hz),
7.35-7.50 (m, 2H), 7.99 (s, 1H), 8.11 (s, 1H), 9.79 (s, 1H), 12.94
(s, 1H).
[0498] I-81
[0499] mp: 261-262.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.21-1.57 (m,4H),1.27 (s,9H),1.78-2.02 (m,4H),
2.17-2.30 (m, 1H), 2.96-3.16 (m, 1H), 6.34 (s,1H), 6.80 (d, 1H,
J=8.7 Hz), 7.14-7.32 (m, 3H), 7.85 (s, 1H), 9.58 (s, 1H), 10.95 (s,
1H).
[0500] I-82
[0501] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.86 (s, 18H),
1.24-1.37 (m, 2H),1.37 (s,9H),1.56-1.74 (m, 2H), 1.95-2.19 (m, 5H),
3.18-3.32 (m, 1H), 3.44 (t, 4H, J=6.3 Hz), 3.70 (t, 4H, J=6.3 Hz),
4.39 (d, 1H, J=9.0 Hz), 6.59 (d, 2H, J=9.0 Hz), 7.31 (d, 2H, J=8.7
Hz), 7.43 (s, 1H).
[0502] I-83
[0503] mp: 264-265.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.52 (m, 4H), 1.78-1.88 (m,2H),
1.90-2.00 (m, 2H), 2.14-2.26 (m, 1H), 2.96-3.14 (m, 1H), 6.72-6.82
(m, 2H), 6.99 (t, 4H, J=7.8 Hz), 7.18 (t, 2H, J=7.5 Hz), 7.46 (d,
2H, J=9.0 Hz), 8.00 (s, 1H), 9.65 (s, 1H).
[0504] I-84
[0505] mp: 257.degree. C. (dec.). .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.23-1.57 (m, 4H), 1.27 (s, 9H), 1.8:3-2.03 (m, 4H),
2.23-2.35 (m, 1H), 2.98-3.15 (m, 1H), 6.80 (d, 1H, J=8.1 Hz), 7.87
(d, 2H, J=9.0 Hz), 8.34 (d, 2H, J=9.0 Hz), 9.21 (s, 1H), 10.20 (s,
1H).
[0506] I-85
[0507] mp: 256-258.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.22-1.53 (m, 4H), 1.26 (s, 9H), 1.79-2.01 (m, 4H),
2.25 (s, 3H), 2.28-2.42 (m, 1H), 2.97-3.02 (m, 1H), 6.71 (d, 1H,
J=0.9 Hz), 6.80 (d, 1H, J=8.1 Hz), 11.91 (s, 1H).
[0508] I-86
[0509] mp: 228-230.degree. C. .sup.1H-NMR (CD.sub.3OD) .delta.ppm:
1.36 (s, 9H), 1.36-1.48 (m, 2H), 1.55-1.70 (m, 2H), 1.87-1.98 (m,
2H), 2.08-2.17 (m, 2H), 2.20-2.32 (m, 1H), 3.15-3.27 (m, 1H),
3.50(t, 4H, J=5.7 Hz), 3.69 (t, 4H, J=5.7 Hz), 6.72 (d, 2H, J=9.0
Hz), 7.29-7.33 (m, 2H).
[0510] I-87
[0511] mp: 18.3-184.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.27-1.48 (m, 4H), 1.73-1.89 (m, 4H),
1.90-2.00 (m, 2H), 2.16-2.28 (m, 1H), 2.28 (t, 2H, J=7.5 Hz),
2.51-2.54 (m, 2H), 2.97-3.13 (m, 1H), 3.58 (s, 3H), 6.79 (d, 1H,
J=8.7 Hz), 7.08 (d, 2H, J=8.7 Hz), 7.49 (d, 2H, J=8.4 Hz), 9.73 (s,
1H).
[0512] I-88
[0513] mp: 217-218.degree. C. .sup.1H-NMR (CD.sub.3OD) .delta.ppm:
1.36 (S 9H), 1.36-1.46 (m, 2H), 1.55-1.69 (m, 2H) 1.83-2.00 (m,
4H), 2.07-2.18 (m, 2H), 2.26-2.36 (m, 3H), 2.61 (t, 2H, J=7.5 Hz),
3.14-3.26 (m, 1H), 7.13 (d, 2H, J=8.1 Hz), 7.44 (d, 2H, J=8.1
Hz).
[0514] I-89
[0515] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.08 (d, 6H, J=3.3 Hz),
0.88(s, 9H), 1.21-1.36 (m, 2H), 1.39 (s, 9H), 1.61-1.74 (m, 2H),
1.88-2.23 (m, 6H), 3.06-3.11 (m, 1H), 3.24-3.74 (m, 4H), 3.92 (d,
1H, J=9.6 Hz), 4.48-4.56 (m, 1H), 6.47 (d, 2H, J=9.0 Hz), 7.17 (s,
1H), 7.32 (d, 2H, J=9.0 Hz).
[0516] I-90
[0517] mp: amorphous. .sup.1H-NMR (CD.sub.3OD) .delta.ppm: 1.36 (s,
9H), 1.36-1.47 (m, 2H), 1.56-1.70 (m, 3H), 1.88-2.30 (m, 6H),
3.05-3.49 (m, 5H), 4.50 (brs, 1H), 6.50 (d, 2H, J=9.0 Hz), 7.29 (d,
2H, J=9.0 Hz).
[0518] I-91
[0519] mp: 105-106.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.92(t, 3H, J=7.3 Hz), 1.25-1.27(m, 2H), 1.36(d, 6H, J=6.9 Hz),
1.51-1.59(m, 2H), 2.56(t, 2H, J=7.8 Hz), 3.27(sept, 1H, J=6.9 Hz),
7.12(d, 2H, J=8.6 Hz), 7.32(t, 1H, J=7.8 Hz), 7.45(brd, 1H, J=7.8
Hz), 7.53(d, 2H, J=8.6 Hz), 7.58(d, 1H, J=7.8 Hz), 7.71-772(m, 2H),
8.27(s, 1H).
[0520] I-92
[0521] mp: 163-164.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93(t, 3H, J=7.3 Hz), 1.32-1.39(m, 2H), 1.55-1.65(m, 2H), 1.87(s,
3H), 1.95(s, 3H), 2.60(t, 2H, J=7.6 Hz), 7.07(d, 2H, J=8.4 Hz),
7.18(d, 2H, J=8.5 Hz), 7.54(d, 2H, J=8.5 Hz), 7.91(brs, 1H),
8.18(cl, 2H, J=8.4 Hz), 8.77(s, 1H).
[0522] I-93
[0523] mp: 173.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93(t, 3H, J=7.3 Hz), 1.32-1.40(m, 2H), 1.39(d, 6H, J=6.9 Hz),
1.55-1.62(m, 2H), 2.60(t, 2H, J=7.8 Hz), 3.13(sept, 1H, J=6.9 Hz),
4.39(d, 2H, J=6.3 Hz), 4.45(t, 1H, J=6.3 Hz), 7.18(d, 2H, J=8.7
Hz), 7.46(d, 2H, J=8.7 Hz), 7.54 (d, 2H, J=8.7 Hz), 7.80(s, 1H),
7.85(d, 2H, J=8.7 Hz).
[0524] I-94
[0525] mp: 1.59-160.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93(t, 3H, J=7.3 Hz), 1.32-1.39(m, 2H), 1.54-1.80(m, 2H), 1.79(s,
3H), 1.80(s, 3H), 2.60t, 2H, J=7.7 Hz), 3.18(s, 3H), 7.18(d, 2H,
J=8.5 Hz), 7.30(d, 2H, J=8.8 Hz), 7.52(d, 2H, J=8.5 Hz), 7.70(brs,
1H); 7.84(d, 2H, J=8.8 Hz), 8.77(s, 1H).
[0526] I-95
[0527] mp:177-178.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.94(t, 3H, J=7.2 Hz). 1.31-1.48(m, 8H), 1.54-1.66(m, 2H), 2.55(s,
3H), 2.62(t, 2H, J=7.6 Hz), 3.92(sept, 1H, J=6.6Hz), 7.20(d, 2H,
J=8.45 Hz), 7.74(d, 2H, J=8.5Hz), 9.01(brs, 1H), 9.17(s, 1H).
[0528] I-96
[0529] mp: 220-223.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93(t, 3H, J=7.3 Hz), 1.28-1.42(m, 2H), 1.50(d, 6H, J=6.8 Hz),
1.54-1.65(m, 2H), 2.62(t, 2H, J=7.6 Hz), 4.08(sept, 1H, J=7.1 Hz),
7.20(d, 2H, J=8.5 Hz), 7.48(d, 2H, J=8.5 Hz), 7.71(brs, 1H),
8.51(brs, 1H), 8.95(s, 1H).
[0530] I-97
[0531] mp: 195-197.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.91(t, 3H, J=7.6 Hz), 0.94(t, 3H, J=7.3 Hz), 1.32-1.44(m, 6H),
1.54-1.64(m, 2H), 1.66-1.78(m, 2H), 2.62(t, 2H, J=7.7 Hz),
2.86(brs, 2H), 3.98(sept, 1H, J=7.1 Hz), 7.19(d, 2H, J=8.5 Hz),
7.63(d, 2H, J=8.4 Hz), 8.72(brs, 1H), 8.81(brs, 1H).
[0532] I-98
[0533] mp: 216-218.degree. C. .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD)
.delta.ppm: 0.93(t, 3H, J=7.4 Hz), 1.29-1.40(m, 2H), 1.43(d, 2H,
J=6.9 Hz), 1.51-1.63(m, 2H), 2.60(t, 2H, J=7.8 Hz), 3.65(sept, 1H,
J=6.9 Hz), 7.18(d, 2H, J=8.5 Hz), 7.22(d, 1H, J=8.8 Hz), 7.55(d,
2H, J=8.5 Hz), 8.18(dd, 1H, J=8.8, 2.4 Hz), 8.63(d, 1H, J=2.4
Hz).
[0534] I-99
[0535] mp: 201-202.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.22-1.40(m, 2H), 1.49(d, 2H,
J=7.1 Hz), 1-1.63(m, 2H), 2.59(t, 2H, J=7.7 Hz), 4.22(sept, 1H,
J=7.1 Hz), 7.16(d, 2H, J=8.4 Hz), 7.41(brs, 1H), 7.52(d, 2H,
J=8.4Hz), 8.10(brs, 1H), 8.13(d, 1H, J=2.2 Hz), 8.61(brs, 1H).
[0536] I-100
[0537] mp: 160-162.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93(t, 3H, J=7.3 Hz), 1.22-1.42(m, 2H), 1.45(d, 2H, J=6.9 Hz),
1.51-1.63(m, 2H), 2.61(t, 2H, J=7.8 Hz), 3.37(sept, 1H, J=6.9 Hz),
6.89(brs, 1H), 7.19(d, 2H, J=8.4 Hz), 7.65(d, 2H, J=8.4 Hz),
7.80(dd, 1H, J=8.4, 2.4 Hz), 8.27(d, 1H, J=8.4 Hz), 8.45(d, 1H,
J=2.4Hz), 9.75(1brs, 1H).
[0538] I-101, I-214
[0539] mp: 192-194.degree. C. 1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.27-1.41(m, 2H), 1.35(s, 9H),
1.50-1.66(m, 2H), 2.60(t, 2H, J=7.6 Hz), 5.58(brs, 1H), 7.07(d, 2H,
J=8.5 Hz), 7.17(d, 2H, J=8.5Hz), 7.52(d, 2H, J=8.5Hz), 7.71(brs,
1H), 7.79(d, 2H, J=8.5 Hz).
[0540] I-102
[0541] mp: 216-217.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.26-1.42(m, 2H), 1.45(s, 9H),
1.70-1.83(m, 2H), 2.60(t, 2H, J=7.7 Hz), 6.42(brs, 1H), 7.18(d, 2H,
J=8.5 Hz), 7.35(d, 2H, J=8.5 Hz), 7.51(d, 2H, J=8.5 Hz), 7.68(brs,
1H), 7.82(d, 2H, J=8.5 Hz).
[0542] I-103
[0543] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 0.91(t, 3H, J=7.3 Hz),
1.28-1.36(m, 2H), 1.32(d, 6H, J=6.9 Hz), 1.49-1.59(m, 2H), 2.54(t,
2H, J=7.7 Hz), 3.23(sept, 1H, J=6.9 Hz), 3.46(s, 3H), 6.76(brs,
1H), 6.91(d, 2H, J=8.2 Hz), 6.99(d, 2H, J=8.8 Hz), 7.03(d, 2H,
J=8.2 Hz), 7.25(d, 2H, J=8.8 Hz).
[0544] I-104
[0545] mp: 182-183.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.28-1.40(m, 2H), 1.51-1.63(m,
2H), 1.64-1.88(m, 4H), 1.90-2.23(m, 4H), 2.60(t, 2H, J=7.6 Hz),
3.39(m, 1H), 6.16(brs, 1H), 7.07(d, 2H, J=8.5 Hz), 7.16(d, 2H,
J=8.5 Hz), 7.52(d, 2H, J=8.5Hz), 7.74(brs, 1H), 7.77(d, 2H, J=8.5
Hz).
[0546] I-105
[0547] mp:190-191.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.28-1.41(m, 2H), 1.52-1.69(m,
4H), 1.75-1.90(m, 2H), 1.92-2.07(m, 4H), 2.58(t, 2H, J=7.6 Hz),
3.59(m, 1H), 6.53(brs, 1H), 7.18(d, 2H, J=8.5 Hz), 7.31(d, 2H,
J=8.5 Hz), 7.52(d, 2H, J=8.5 Hz), 7.67(brs, 1H), 7.84(d, 2H, J=8.5
Hz).
[0548] I-106
[0549] mp: 194-197.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.22-1.41(m, 2H), 1.53-1.65(m,
2H), 1.90(s, 6H), 2.60(t, 2H, J=7.8 Hz), 6.86(brs, 1H), 7.18(d, 2H,
J=8.5 Hz), 7.43(d, 2H, J=8.5 Hz), 7.51(d, 2H, J=8.5 Hz), 7.71(brs,
1H), 7.84(d, 2H, J=8.5 Hz).
[0550] I-107
[0551] mp: 211-212.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 1.24-1.40(m, 2H), 1.50-1.62(m,
2H), 2.60(t, 2H, J=7.6 Hz), 6.19(brs, 1H), 7.17(d, 2H, J=8.5 Hz),
7.18(d, 2H, J=8.5 Hz), 7.51(d, 2H, J=8.5 Hz), 7.66(brs, 1H),
7.86(d, 2H, J=8.5 Hz).
[0552] I-108
[0553] mp: 298-300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 0.90(t, 3H, J=7.3 Hz), 1.22-1.39(m, 2H), 1.48-1.60(m,
2H), 2.54(t, 2H, J=7.3 Hz), 7.04(d, 2H, J=8.8 Hz), 7.12(d, 2H,
J=8.5 Hz), 7.64(d, 2H, J=8.5 Hz), 7.69(d, 2H, J=8.8 Hz), 9.80(s,
1H).
[0554] I-109
[0555] mp: 122-123.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.90(t 3H, J=7.4 Hz), 0.97(t, 3H, J=7.7 Hz),
1.26-1.38(m, 2H), 1.30(s, 6H), 1.50-1.66(m, 4H), 1.72-1.83(m, 4H),
2.34(t, 2H, J=7.1 Hz), 2.55(t, 2H, J=7.6 Hz), 3.19(q, 1H, J=6.0
Hz), 4.60(brs, 1H), 7.08(d, 2H, J=8.5 Hz), 7.42(d, 2H, J=8.5 Hz),
7.85(s, 1H).
[0556] I-110
[0557] mp: 109-110.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91(t, 3H, J=7.4 Hz), 1.10(d, 6H, J=6.7 Hz),
1.29-1.38(m, 2H), 1.55(s, 9H), 1.60-1.70(m, 2H), 1.78-1.89(m, 2H),
2.26(m, 1H), 2.39(t, 2H, J=7.0 Hz), 2.57(t, 2H, J=7.7 Hz), 2.90(d,
2H, J=6.6 Hz), 3.16(brs, 1H), 4.24(brs, 1H), 7.12(d, 2H, J=8.5 Hz),
7.40(d, 2H, J=8.5 Hz).
[0558] I-111
[0559] mp 64-65.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91(t, 3H, J=7.3 Hz), 1.02(t, 3H, J=7.5 Hz), 1.35(d,
3H, J=6.7 Hz), 1.26-1.38(m, 2H), 1.48-1.69(m, 5H), 1.76-1.87(m,
2H), 2.04(m, 1H), 2.38(t, 2H, J=7.3 Hz), 2.56(t, 2H, J=7.6 Hz),
2.91(m, 1H), 3.16(brs, 2H), 4.42(brs, 1H), 7.11(d, 2H, J=8.5 Hz),
7.42(d, 2H, J=8.5 Hz), 7.47(brs, 1H).
[0560] I-112
[0561] mp 79-80.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.36(s, 9H), 1.52-1.62(m, 2H), 1.67-1.76(m, 2H), 2.22(t,
2H, J=7.4Hz), 3.16(q, 2H, J=6.3 Hz), 3.78(s, 3H), 4.33(d, 2H, J=5.4
Hz), 4.62(brs, 1H), 6.20(brs, 1H), 6.85(d, 2H, J=8.8 Hz), 7.19(d,
2H, J=8.8 Hz).
[0562] I-113
[0563] mp: 125-126.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.38(s, 9H), 1.62-1.70(m, 2H), 1.76-1.88(m, 2H), 2.46(t,
2H, J=7.4 Hz), 3.22(q, 2H, J=6.1 Hz), 4.22(t, 1H, J=6.1 Hz),
7.24(dd, 1H, J=8.9, 2.3 Hz), 7.36(d, 1H, J=2.3 Hz), 7.65(brs, 1H),
8.29(d, 1H, J=8.9 Hz).
[0564] I-114
[0565] mp: 89-91.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.92 (t, 3H, J=7.0 Hz), 1.06 (d, 6H, J=7.0 Hz), 1.36 (m,
1H), .50-1.72 (m,5H), 1.94-2.06 (m, 2H), 2.26 (m, 1H), 2.60 (t, 2H,
J=7.7 Hz), 2.84 (t, 2H, J=7.7 Hz), 2.93 (d, 2H, J=6.3 Hz), 3.20 (t,
2H, J=6.6 Hz), 4.30 (brs, 1H), 7.19 (d, 2H, J=8.5 Hz), 7.63 (d, 2H,
J=8.5 Hz), 9.15(brs, 1H).
[0566] I-115
[0567] mp: 94-95.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.92 (t, 3H, J=7.5 Hz), 1.03 (t, 3H, J=7.5 Hz),
1.23-1.40 (m ,5H), 1.42-1.65 (m, 6H), 1.75 (m, 1H), 2.02 (m, 1H),
2.24 (t, 2H, J=7.0 Hz), 2.59 (t, 2H, J=8.0 Hz), 2.90 (m, 1H), 3.14
(q, 2H, J=6.6 Hz), 4.20 (m, 1H), 4.40 (d, 2H, J=5.4 Hz), 5.70 (brs,
1H), 7.14 (d, 2H, J=8.1 Hz), 7.18(d, 2H, J=8.1 Hz).
[0568] I-116
[0569] mp: 89-91.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.97 (t, 3H, J=7.3 Hz), 1.02 (t, 3H, J=7.5 Hz), 1.35 (d,
3H, J=7.0 Hz), 1.40-1.90 (m ,9H), 2.04 (m, 1H), 2.37 (t, 2H, J=7.0
Hz), 2.90 (m, 1H), 3.17 (q, 2H, J=6.6 Hz), 3.93 (t 2H, J=6.6 Hz),
4.32 (m, 1H), 6.84 (d, 2H, J=9.0 Hz), 7.31 (brs, 1H), 7.40 (d, 2H,
J=9.0 Hz).
[0570] I-117
[0571] mp: 110-111.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.02 (t, 3H, J=7.5 Hz), 1.34 (d, 3H, J=6.6 Hz),
1.45-1.70 (m, 3H), 1.75-1.85 (m, 2H), 2.05 (m, 1H), 2.36 (t, 2H,
J=7.5 Hz), 2.90 (m, 1H), 3.16 (q, 2H, J=6.6 Hz), 3.78 (s, 3H), 4.50
(m, 1H), 6.84 (d, 2H, J=6.8 Hz), 7.42 (d, 2H, J=6.8 Hz), 7.48 (brs,
1H).
[0572] I-118
[0573] mp: 113-115.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.92 (t, 3H, J=7.0 Hz), 1.20-1.34 (m, 1H), 1.37 (d, 6H,
J=7.0 Hz), 1.48-1.70 (m, 3H), 2.43 (q, 2H, J=6.6 Hz), 2.58 (t, 2H,
J=7.7 Hz), 3.10-3.31 (m, 3H), 4.75 (m, 1H), 6.04 (d, 1H, J=15.0
Hz), 6.77 (dt, 1H, J=7.7, 15.0 Hz), 7.14 (d, 2H, J=8.4 Hz), 7.55
(d, 2H, J=8.4 Hz), 7.85 (brs, 1H).
[0574] I-119
[0575] mp: 139-140.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.19(s, 9H), 1.47(m, 2H), 1.61(m, 2H), 2.18(t, 2H, J=7.6
Hz), 3.03(q, 2H, K=6.3 Hz), 4.09(t, 1H, J=5.9 Hz), 6.85(brd, 1H,
J=8.0 Hz), 7.00(t, 1H, J=8.0 Hz), 7.16(brd, 1H, J=8.0), 7.48(brs,
1H), 7.57(brs, 1H).
[0576] I-120
[0577] mp: 183.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91(t, 3H, J=7.3 Hz), 1.20-1.58(m, 6H), 1.40(s, 9H),
2.07(dd, 1H, J=12.9, 3.1 Hz), 2.52(t, 2H, J=7.7 Hz), 2.95(dd, 2H,
J=11.5, 2.5 Hz), 3.46(m, 1H), 3.88-4.07(m, 3H), 6.47(s, 1H),
7.08(d, 2H, J=8.5 Hz), 7.22(d, 2H, J=8.5 Hz).
[0578] I-121
[0579] mp: 163-166.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91(t, 3H, J=7.3 Hz), 1.32-1.62(m, 6H), 1.45(s, 9H),
1.95-2.07(m, 3H), 2.20(m, 1H), 2.46(td, 1H, J=10.4, 3.7 Hz),
2.37(t, 2H, J=7.6 Hz), 3.43(brd, 2H, J=10.4 Hz), 4.80(s, 1H),
7.12(d, 2H, J=8.4 Hz), 7.14(s, 1H), 7.39(d, 2H, J=8.4 Hz).
[0580] I-122
[0581] mp: 188-189.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91 (t, 3H, J=7.5 Hz), 1.25-1.41 (m ,2H), 1.42 (s, 9H),
1.50-1.62 (m, 2H), 1.78-1.95 (m, 4H), 2.00-2.20 (m, 6H), 2.57 (t,
2H, J=7.5 Hz), 3.99(brs, 1H), 7.10 (brs, 1H), 7.12 (d, 2H, J=6.5
Hz), 7.41 (d, 2H, J=6.5 Hz).
[0582] I-123
[0583] mp: 197-198.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.91 (t, 3H, J=7.5 Hz), 1.24-1.40 (m, 2H), 1.39 (s, 9H),
1.50-1.70 (m, 2H), 1.99 (brs, 12H), 2.56 (t, 2H, J=7.5 Hz), 3.47
(brs, 1H), 7.10 (s, 1H), 7.11 (d, 2H, J=8.5 Hz), 7.38 (d, 2H, J=8.5
Hz).
[0584] I-124
[0585] mp: 258-260.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.40 (m, 2H), 1.41 (s, 9H), 1.62-1.81 (m, 2H),
2.03-2.35 (m, 5H), 2.37 (s, 3H), 2.71 (s, 3H), 3.32 (m, 1H), 3.64
(d, 1H, J=8.4 Hz), 7.08 (brs, 1H), 7.24 (m, 1H), 7.33 (m, 2H), 7.60
(d. 1H, J=8.1 Hz), 7.77 (s, 1H), 7.80 (d, 1H, J=8.4 Hz), 8.14 (m,
1H).
[0586] I-125
[0587] mp: 297-299.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.27 (s, 9H), 1.28-1.56 (m, 4H), 1.80-2.01 (m, 4H), 2.47
(m, 1H), 2.76 (brs, 1H), 3.05 (m, 2H), 6.78 (d, 1H, J=9.0 Hz), 7.23
(d, 1H, J=9.0 Hz), 7.46 (dd, 1H, J=2.0, 9.0 Hz), 8.03 (d, 1H, J=2.0
Hz).
[0588] I-126
[0589] mp: 198-199.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.39 (m, 2H), 1.40 (s, 9H), 1.60-1.79 (m, 2H),
1.98-2.35 (m, 5H), 3.30 (m, 1H), 3.67 (d, 1H, J=9.6 Hz), 5.89 (tt,
1H, J=3.0, 50.0 Hz), 6.97 (d, 1H, J=7.8 Hz), 7.21 (s, 1H),
7.30-7.40 (m, 2H), 7.55 (s, 1H)
[0590] I-127
[0591] mp: 262-264.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.41 (s, 9H), 1.60-1.80 (m, 2H),
2.00-2.36 (m, 5H), 2.57 (s, 3H), 3.33 (m, 1H), 3.62 (d, 1H, J=8.7
Hz), 7.28 (brs, 1H), 7.62 (d, 2H, J=8.7Hz), 7.94 (d, 2H, J=8.7
Hz).
[0592] I-128
[0593] mp: 252-254.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.39 (m, 2H), 1.40 (s, 9H), 1.58-1.79 (m, 2H),
1.99-2.30 (m, 5H), 2.46 (s, 3H), 3.32 (m, 1H), 3.64 (m, 1H), 7.11
(brs, 1H), 7.23 (d, 2H, J=9.0 Hz), 7.44 (d, 2H, J=9.0 Hz).
[0594] I-129
[0595] mp: >300.degree. C. .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD)
.delta.ppm:1.30-1.45(m, 2H), 1.42(s, 9H), 1.70-1.88(m, 2H),
2.10-2.37(m. 4H), 2.52(m, 1H), 3.34(m, 1H), 7.43-7.54(m, 3H),
7.82(d, 1H, J=6.7 Hz), 7.88(d, 1H, J=8.5 Hz), 7.98-8.07(m, 2H),
8.44(s, 1H), 8.46(s, 1H).
[0596] I-130
[0597] mp: 123-124.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.34(m, 2H), 1.40(s, 9H), 1.62-1.75(m, 2H),
2.00-2.28(m, 5H), 3.31(m, 1H), 3.61(d, 1H, J=9.5 Hz), 5.59(s, 1H),
7.17(s, 1H), 7.30-7.37(m, 6H), 7.41(d, 1H, J=8.5 Hz), 7.84(d, 1H,
J=2.1 Hz).
[0598] I-131
[0599] mp: 202-204.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.27-1.38(m, 2H), 1.38(s, 9H), 1.62-1.75(m, 2H),
1.97-2.04(m, 2H), 2.18-2.27(m, 3H), 3.26(m, 1H), 3.81(s, 3H),
4.62(d, 1H, J=7.9 Hz), 7.12(d, 1H, J=7.8 Hz), 7.40(t, 1H, J=7.8
Hz), 7.51(s, 3H), 7.61(d, 1H, J=7.8 Hz), 7.71(s, 1H), 8.21(brs,
1H).
[0600] I-132
[0601] mp: 236-237.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.23-1.43(m, 2H), 1.41(s, 9H), 1.66-1.80(m, 2H),
2.08-2.12(m, 2H), 2.23-2.31(m, 3H), 3.34(m, 1H), 3.87(d, 1H, J=9.5
Hz), 4.02(s, 3H), 7.30(td, 1H, J=7.3, 1.1 Hz), 7.36(s, 1H),
7.39(td, 1H, J=7.3, 1.5 Hz), 7.53(brd, 1H, J=7.3 Hz), 7.84(brd, 1H,
J=7.3 Hz), 8.05(s, 1H), 8.73(s, 1H).
[0602] I-133
[0603] mp: 198-200.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.93(t, 3H, J=7.3 Hz), 0.97(t, 3H, J=6.7 Hz),
1.18-1.81(m, 7H), 1.39(s, 9H), 1.98-2.05(m, 2H), 2.21-2.24(m, 3H),
3.29(m, 1H), 4.00(dd, 1H, J=10.7, 6.7 Hz), 4.09(dd, 1H, J=10.7, 6.1
Hz), 4.27(d, 1H, J=9.8 Hz), 6.37(d, 1H, J=15.9 Hz), 7.47(d, 2H,
J=8.5 Hz), 7.59(d, 2H, J=8.5 Hz), 7.62(d, 1H, J=15.9 Hz), 7.83(brs,
1H).
[0604] I-134
[0605] mp: 212-213.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.21-1.32(m, 2H), 1.39(s, 9H), 1.59-1.(m, 2H),
1.99-2.04(m, 2H), 2.10-2.26(m, 3H), 3.26(m, 1H), 3.72(d, 1H, J=9.6
Hz), 6.74(m, 1H), 7.02(d, 2H, J=7.4 Hz), 7.11(t, 1H, J=7.4 Hz),
7.13-7.19(m, 2H), 7.22-7.26(m, 2H), 7.34(t, 2H, J=7.4 Hz).
[0606] I-135
[0607] mp: 294-296.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.27 (s, 9H), 1.28-1.55 (m, 4H), 1.81-2.05 (m, 4H), 2.26
(m, 1H), 2.98-3.20 (m, 2H), 6.78 (d, 1H, J=9.0 Hz), 7.31 (t, 1H,
J=7.5 Hz), 7.54-7.72 (m, 5H), 7.94 (brs, 1H).
[0608] I-136
[0609] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.28 (s, 9H), 1.29-1.59 (m, 4H), 1.81-2.02 (m, 4H), 2.27
(m, 1H), 3.06 (m, 1H), 6.81 (d, 1H, J=8.7 Hz), 7.38 (t, 1H, J=7.2
Hz), 7.48 (t, 2H, J=7.2 Hz), 7.62-7.81 (m, 10H), 9.93 (brs,
1H).
[0610] I-137
[0611] mp: 291-292.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.25-1.39 (m, 2H), 1.41 (s, 9H), 1.61-1.80 (m, 2H),
2.01-2.36 (m, 5H), 3.32 (m, 1H), 3.63 (d, 1H, J=9.3 Hz), 7.20 (brs,
1H), 7.53-7.74 (m, 8H).
[0612] I-138
[0613] mp: 259-262.degree. C. .sup.1H-NMR (CD.sub.3OD)
.delta.ppm:1.40 (s, 9H), 1.40-1.80 (m, 4H), 2.00-2.30 (m, 4H), 2.45
(m, 1H), 3.00 (s, 3H), 3.15-3.30 (m, 2H), 7.90 (d, 1H, J=8.4 Hz),
8.12 (d, 1H, J=9.0 Hz), 8.39 (d, 1H, J=9.0 Hz), 8.72 (s, 1H), 8.92
(d, 1H, J=8.4 Hz), 10.4 (s, 1H).
[0614] I-139
[0615] mp: 265-268.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.25-1.40(m, 2H), 1.40(s, 9H), 168-1.81(m, 2H),
2.05-2.10(m, 2H), 2.23-2.37(m, 3H), 3.32(m, 1H), 4.27(d, 1H, J=9.1
Hz), 7.53(t, 1H, J=7.9 Hz), 7.63(td, 1H, J=7.9, 1.4 Hz), 7.77(d,
1H, J=7.9 Hz), 8.03(d, 1H, J=7.9 Hz), 8.37(brs, 1H), 8.85-8.86(m,
2H).
[0616] I-140
[0617] mp: 258-260.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.40 (m, 2H), 1.41 (s, 9H), 1.52-1.85 (m, 2H),
2.03-2.35 (m, 5H), 3.34 (m, 1H), 3.75 (m, 1H), 7.35-7.66 (m, 3H),
8.05 (d, 1H, J=9.0 Hz), 8.11 (d, 1H, J=9.0 Hz). 8.40 (brs, 1H),
8.83 (s, 1H).
[0618] I-141
[0619] mp: 205-206.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.37(m, 2H), 1.40(s, 9H), 1.43-1.62(m, 2H),
1.90-2.01(m, 2H), 2.02-2.23(m, 3H), 3.27(m, 1H), 3.63(d, 1H, J=9.6
Hz), 3.70(s, 3H), 6.64(d, 1H, J=8.8 Hz), 7.28-7.41(m, 5H),
7.45(brs, 1H), 8.26(d, 1H, J=8.8 Hz).
[0620] I-142
[0621] mp: 277-280.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.23-0.34(m, 2H), 1.34(s, 9H), 1.34-1.55(m, 5H),
1.76-1.80(m, 2H), 2.97(m, 1H), 3.31(d, 1H, J=9.6 Hz), 7.18(s, 1H),
7.50-7.59(m, 4H), 7.77(dd, 1H, J=7.4, 1.0 Hz), 7.91-7.98(m, 2H),
8.39(dd, 1H, J=7.4, 1.9 Hz).
[0622] I-143
[0623] mp: 202-203.degree. C. .sup.1H-NMR(CDCl.sub.3)
.delta.ppm:1.23-1.40(m, 2H), 1.40(s, 9H), 1.57-1.71(m, 2H),
2.05-2.10(m, 2H), 2.18-2.28(m, 3H), 3.31(m, 1H), 3.91(s, 3H),
3.93(s, 3H), 4.05(d, 1H, J=9.5 Hz), 8.15(s, 1H), 9.56(s, 1H).
[0624] I-144
[0625] mp: 177-178.degree. C. .sup.1H-NMR(CDCl.sub.3)
.delta.ppm:1.27-1.39(m, 2H), 1.40(s, 9H), 1.65-1.79(m, 2H),
2.04-2.07(m, 2H), 2.12-2.34(m, 3H), 3.22(m, 1H), 3.93(d, 1H, J=9.1
Hz), 6.90-7.03(m, 3H), 7.25(m, 1H), 7.77(dd; 1H, J=4.9, 1.7 Hz),
7.81(brs, 1H), 8.72(dd, 1H, J=7.8, 1.5 Hz).
[0626] I-14.5
[0627] mp: >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.30(s, 9H), 1.44-1.70(m, 4H), 2.05-2.19(m, 4H), 2.73(m,
1H), 3.18(m, 1H), 6.86(d, 1H, J=8.8 Hz), 7.62(t, 2H, J=8.5 Hz),
7.86(t, 2H, J=8.5 Hz), 7.89(d, 2H, J=8.5 Hz), 8.16(d, 2H, J=8.5
Hz).
[0628] I-146
[0629] mp: 240-242.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.26-1.53(m, 4H), 1.27(s, 9H), 1.74-1.83(m, 2H),
1.90-1.97(m, 2H) 2.26(m, 1H), 3.04(m, 1H), 6.59(brs, 1H),
6.74-6.79(m, 3H), 7.74(s, 1H), 10.32(s, 1H), 12.80(s, 1H).
[0630] I-147
[0631] mp: 167- 169.degree..degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 1.05-1.28 (m, 2H), 1.38 (s, 9H), 1.47-1.70 (m, 2H),
1.80-2.00(m, :3H), 2.13-2.25 (m, 2H), 2.75 (t, 2H, J=6.9 Hz), 3.24
(m, 1H), 3.49 (dt, 2H, J=6.3, 6.9 Hz), 3.58 (d, 1H, J=8.7 Hz), 3.87
(s, 6H), 5.40 (brs, 1H), 6.71 (m, 2H), 6.82 (d, 1H, J=8.7 Hz).
[0632] I-148
[0633] mp: 171-172.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.16-1.38 (m, 2H), 1.39 (s, 9H), 1.50-1.79 (m, 4H),
1.85-2.02(m, 3H), 2.15-2.30 (m, 2H), 2.35-2.56 (m, 6H), 3.25 (m,
1H), 3.33 (q, 2H, J=6.0 Hz), 3.63 (d, 1H, J=9.0 Hz), 3.72 (t, 4H,
J=4.6 Hz), 6.77 (brs, 1H).
[0634] I-149
[0635] .sup.1H-NMR (CDCl.sub.3) .delta.ppm:1.20-1.36 (m, 2H), 1.28
(t, 3H, J=7.2 Hz), 1.39 (s, 9H), 1.45-1.70 (m, 2H), 1.85-2.30 (m,
7H), 2.43 (s, 3H), 3.05-3.42 (m, 3H), 3.46-3.80 (m, 3H), 7.31 (d,
1H, J=7.2 Hz), 7.40-7.52 (m, 3H), 8.18 (brs, 1H).
[0636] I-150
[0637] mp: 203-204.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.15-1.37 (m, 2H), 1.39 (s, 9H), 1.42-1.70 (m, 2H),
1.85-2.29 (m, 5H), 2.76 (t, 2H, J=6.0 Hz), 3.26 (m, 1H), 3.49 (q,
2H, J=6.0 Hz), 3.61 (m, 1H), 4.03 (s, 2H), 5.88 (brs, 1H), 7.15
(dd, 1H, J=7.0, 8.8 Hz), 0-7.35 (m, 2H).
[0638] I-151
[0639] mp: 181-183.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.64 (m, 2H),
1.88-2.05(m, 3H), 2.15-2.25 (m, 2H), 2.69 (t, 2H, J=6.0 Hz), 3.28
(m, 1H), 3.47 (q, 2H, J=6.0 Hz), 3.58 (d, 1H, J=9.9 Hz), 3.87 (s,
2H), 5.83 (brs, 1H), 7.00 (m, 1H), 7.20 (m, 2H).
[0640] I-152
[0641] mp: 2292-224.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.16-1.37 (m, 2H), 1.39 (s, 9H), 1.49-1.70 (m, 2H),
1.90-2.25 (m, 5H), 3.26 (m, 1H), 3.36 (t, 2H, J=6.4 Hz), 3.66 (dt,
3H, J=6.0, 6.4 Hz), 5.87 (t, 1H, J=6.0 Hz), 7.58 (s, 1H), 7.68 (dd,
1H, J=7.0. 8.5 Hz), 7.83 (dd, 1H, J=7.0, 8.5 Hz), 8.19 (t, 2H,
J=8.5 Hz).
[0642] I-153
[0643] mp: 207-209.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.05-1.25 (m, 2H), 1.38 (s, 9H), 1.40-2.03 (m, 10H),
2.05-2.25 (m, 2H), 2.58 (s, 3H), 2.76 (m, 1H), 3.05-3.35 (m, 2H),
3.97 (d, 1H, J=9.5 Hz), 4.94 (t, 1H, J=4.0 Hz), 8.42 (d, 1H, J=5.5
Hz), 8.97 (d, 1H, J=5.5 Hz).
[0644] I-154
[0645] mp: 184-185.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.05-1.25 (m, 2H), 1.37 (s, 9H), 1.50-1.69 (m, 2H),
1.85-2.05 (m, 3H), 2.10-2.21 (m, 2H), 3.24 (m, 1H), 3.64 (m, 1H),
4.87 (s, 1H), 4.88 (s, 1H), 5.67 (brs, 1H), 7.42 (d, 2H, J=5.5 Hz),
7.52 (m, 2H), 7.78 (m, 1H), 7.82 (m, 1H), 7.95 (d, 1H, J=7.0
Hz).
[0646] I-155
[0647] mp: 208-210.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.26 (s, 9H), 1.27-1.50 (m, 4H), 1.75-2.00 (m, 4H), 2.16
(m, 1H), 2.81 (s, 3H), 3.02 (m, 1H), 6.79 (d, 1H, J=8.5 Hz), 10.00
(s, 1H), 10.66 (s, 1H).
[0648] I-156
[0649] mp: 256-257.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.41 (s, 9H), 1.60-1.81 (m, 2H),
2.01-2.35 (m, 5H), 2.69 (t, 2H, J=6.0 Hz), 3.11 (t, 2H, J=6.0 Hz),
3.30 (m, 1H), 3.61 (d, 1H, J=9.3 Hz), 7.21 (d. 1H, J=8.0 Hz) 7.31
(s, 1H), 7.70 (d, 1H, J=8.0 Hz), 7.99 (s, 1H).
[0650] I-157
[0651] mp: 269-271.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.45(m,2H),1.41(s,9H), 1.70-1.90(m,
2H),2.10-2.45(m, 5H) 3.37 (m, 1H), 3.68 (m, 1H), 7.45 (dd, 1H,
J=4.0, 8.0 Hz), 7.53 brs, 1H), 7.72 (t, 1H, J=8.0 Hz), 7.83 (d, 1H,
J=8.0 Hz), 8.02 (d, 1H, J=8.0 Hz), 8.18(d, 1H, J=8.0 Hz), 8.93 (d,
1H J=4.0 Hz).
[0652] I-158
[0653] mp:253-255.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.40 (m, 2H), 1.42 (s, 9H), 1.60-1.90 (m,2H),
2.06-2.50 (m, 5H), 2.72 (s, 3H), 3.33 (m, 1H), 3.78 (d, 1H, J=9.2
Hz), 7.52 (t, 1H, J=7.0 Hz), 7.62-7.80 (m, 2H), 7.94 (brs, 1H),
8.05 (d, 1H, J=8.5 Hz), 8.20 (s, 1H).
[0654] I-159
[0655] mp: 253-255.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.60-1.80 (m, 2H),
1.98-2.30 (m, 5H), 2.71 (s, 3H), 3.31 (m, 1H), 3.68 (d, 1H, J=9.0
Hz), 7.41 (brs, 1H), 7.61 (d, 2H, J=9.0 Hz), 7.70 (d, 2H, J=9.0
Hz).
[0656] I-160
[0657] mp: 211-212.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.32 (m, 2H), 1.39 (t, 3H, J=7.0 Hz), 1.40 (s, 9H),
1.55-1.79 (m, 2H), 1.98-2.35 (m, 5H), 3.31 (m, 1H), 3.65 (d, 1H,
J=9.5 Hz), 4.03 (q, 2H, J=7.0 Hz), 6.64 (d, 1H, J=8.0 Hz), 6.92 (d,
1H, J=8.0 Hz), 7.10 (s, 1H), 7.19 (t, 1H, J=8.0 Hz), 7.30 (brs,
1H).
[0658] I-161
[0659] mp:202-203.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:.0.96 (t, 1H, J=7.3 Hz), 1.29-1.39 (m, 2H), 1.40 (s,
9H), 1.41-1.58 (m, 2H), 1.60-1.80 (m, 4H), 1.98-2.31 (m, 5H), 3.31
(m, 1H), 3.66 (d, 1H, J=8.5 Hz), 3.96 (t, 2H, J=6.4 Hz), 6.64 (d,
1H, J=8.0 Hz), 6.90 (d, 1H, J=8.0 Hz), 7.11 (s, 1H), 7.19 (t, 1H,
J=8.0 Hz), 7.31 (brs, 1H).
[0660] I-162
[0661] mp: 177-180.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.38 (m, 2H), 1.39 (s, 9H), 1.59-1.78 (m, 2H),
1.95-2.05 (m, 2H), 2.07-2.25 (m, 3H), 3.26 (m, 1H), 3.46 (s, 3H),
4.17 (d, 1H, J=9.5 Hz), 5.15 (s, 2H), 6.77 (d, 1H, J=8.0 Hz),
7.10-7.23 (m, 2H), 7.34 (s, 1H), 7.58 (s, 1H).
[0662] I-163
[0663] mp: 175-178.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H), 1.78-2.00 (m, 4H),
2.22 (m, 1H), 2.96-3.15 (m, 2H), 6.67 (m, 1H), 6.79 (d, 1H, J=8.5
Hz), 7.18 (m, 2H), 7.38 (s, 1H), 9.81 (s, 1H).
[0664] I-164
[0665] mp: 232-233.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.97(t, 3H, J=7.3 Hz), 1.22-1.30(m, 2H), 1.40(s, 2H),
1.40(s, 9H), 1.44-1.51.(m, 2H), 1.67-1.77(m, 4H), 2.02-2.24(m, 5H),
3.22(m, 1H), 3.62(d, 1H, J=9.6 Hz), 4.25(t, 2H, J=6.8 Hz), 6.71(d,
1H, J=8.4 Hz), 7.01(brs, 1H), 7.91(dd, 1H, J=8.4, 3.3 Hz), 8.08(d,
1H, J=3.3 Hz).
[0666] I-165
[0667] mp: 199-200.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.96(t, 3H, J=7.4 Hz), 1.24-1.50(m, 4H), 1.40(s, 9H),
1.67-1.76(m, 3H), 2.03-2.08(m, 2H), 2.24-2.35(m, 3H), 3.29(m, 1H),
3.76(d, 1H, J=9.1 Hz), 3.91(t, 2H, J=6.6 Hz), 6.41(dd, 1H, J=8.8,
2.5 Hz), 6.55(d, 1H, J=2.5 Hz), 6.82(d, 1H, J=8.8 Hz), 7.43(s, 1H),
8.95(s, 1H)
[0668] I-166
[0669] mp: 21.5-218.degree. C. .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD)
.delta.ppm:0.97(t, 3H, J=7.4 Hz), 1.24-1.40(m, 4H), 1.39(s, 9H),
1.42-1.50(m, 2H), 1.54-1.72(m, 2H), 1.76-1.82(m, 2H), 1.91-2.00(m,
2H), 2.06-2.22(m, 3H), 3.24(m, 1H), 4.00(t, 2H, J=6.6 Hz), 6.78(d,
1H, J=8.8 Hz), 6.98(dd, 1H, J=8.8, 2.5 Hz), 7.09(d, 1H, J=8.8
Hz).
[0670] I-167
[0671] mp: 212-213.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.96(t, 3H, J=7.5 Hz), 1.26-1.34(m, 2H), 1.40(s, 9H),
1.45-1.50(m, 2H), 1.68-1.77(m, 4H), 2.03-2.08(m, 2H), 2.17(m, 1H),
2.26-2.29(m, 2H), 3.29(m, 1H), 3.60(d, 1H, J=9.0 Hz), 4.25(t, 2H,
J=6.8 Hz), 6.71(d, 1H, J=8.4 Hz), 7.01(brs, 1H), 7.91(dd, 1H,
J=8.4, 3.3 Hz), 8.08(d, 1H, J=3.3 Hz).
[0672] I-168
[0673] mp: 230-232.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.22-1.35(m, 2H), 1.40(s, 9H), 1.63-1.77(m, 2H),
2.03-2.08(m, 2H), 2.15-2.29(m, 3H), 3.31(m, 1H), 3.63(d, 1H, J=9.3
Hz), 6.89(d, 1H, J=9.4 Hz), 7.10(brd, 2H, J=7.4 Hz), 7.12(brs, 1H),
7.18(t, 1H, J=7.4 Hz), 7.36(brt, 2H, J=7.4 Hz), 8.09-8.15(m,
2H).
[0674] I-169
[0675] mp: 159-160.degree. C. .sup.1H-NMR(CDCl.sub.3)
.delta.ppm:0.97(t, 3H, J=7.3), 1.20-1.35(m, 2H), 1.40(s, 9H),
1.37-1.49(m, 2H), 1.61-1.78(m, 4H), 2.05-2.08(m, 2H), 2.23-2.26(m,
2H), 2.36(s, 3H), 2.97(brs, 1H), 3.32(m, 1H), 3.86(brs, 1H),
4.30(t, 2H, J=6.5 Hz), 6.25(s, 1H), 7.92(brs, 1H).
[0676] I-170
[0677] mp: 180-181.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.88-0.89(m, 2H), 1.39(s, 9H), 1.42-1.60(m, 2H),
1.86-1.90(m, 2H), 2.04-2.09(m, 2H), 2.42(s, 3H), 2.91(m, 1H),
3.20(m, 1H), 3.63(d, 1H, J=9.2 Hz), 6.38(s, 1H), 7.15(m, 2H),
7.28(m, 1H), 7.45(m, 2H), 7.84(brs, 1H).
[0678] I-171
[0679] mp: 173-174.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.98(t, 3H, J=7.5 Hz), 1.29-1.40(m, 2H), 1.40(s, 9H),
1.55(m, 2H), 1.62-1.83(m, 4H), 2.09-2.12(m, 2H), 2.24-2.32(m, 3H),
3.32(m, 1H), 3.63(d, 1H, J=9.5 Hz), 3.99(t, 2H, J=6.4 Hz), 7.22(dd,
1H. J=9.4, 2.7 Hz), 7.66(d, 1H, J=2.7 Hz), 8.63(d, 1H, J=9.4 Hz),
10.17(s, 1H).
[0680] I-172
[0681] mp: 238-242.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.96(t, 3H, J=7.3 Hz), 1.23-1.52(m, 4H), 1.40(s, 9H),
1.61-1.78(m, 4H), 2.05-2.28(m, 5H), 3.30(m, 1H), 3.66(d, 1H, J=9.4
Hz), 3.84(brs, 2H), 3.90(t, 2H, J=6.4 Hz), 6.32-6.35(m, 2H),
6.96(brs, 1H), 6.97(d, 1H, J=9.4 Hz).
[0682] I-173
[0683] mp: 165-166.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.23-1.26(m, 2H), 1.40(s, 9H), 1.67-1.72(m, 2H),
2.01-2.06(m, 2H), 2.11-2.28(m, 3H), 3.31(m, 1H), 3.60(s, 2H),
3.69(s, 3H), 4.02(brs, 1H), 7.01(d, 1H, J=8.0 Hz), 7.25(t, 1H,
J=8.0 Hz), 7.43(d, 1H, J=8.0 Hz), 7.49(brs, 1H), 7.51(brs, 1H).
[0684] I-174
[0685] mp: 264-265.degree. C. .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD)
.delta.ppm: 1.26-1.29(m, 2H), 1.39(s, 9H), 1.62-1.69(m, 2H),
1.96-2.00(m, 2H), 2.18-2.21(m, 3H), 3.25(m, 1H), 3.58(s, 2H),
7.01(d, 1H, J=7.5 Hz), 7.26(t, 1H, J=7.5 Hz), 7.42(brs, 1H),
7.50(d, 1H, J=7.5 Hz).
[0686] I-175
[0687] mp: 90-94.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.16-1.23(m, 2H), 1.37(s, 9H), 1.44-1.56(m, 2H),
1.73-1.85(m, 3H), 2.11-2.15(m, 2H), 3.57(t, 2H, J=6.4 Hz), 3.21(m,
1H), 3.58(m, 2H), 3.84(d, 1H, J=9.3 Hz), 5.56(brs, 1H), 7.01(s,
1H), 7.11(t, 1H, J=7.5 Hz), 7.21(t, 1H, J=7.5 Hz), 7.38(d, 1H,
J=7.5 Hz), 7.59(d, 1H, J=7.5 Hz), 8.24(brs, 1H).
[0688] I-176
[0689] mp: 116-118.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.38 (m, 2H), 1.40 (s, 9H), 1.60-1.79 (m, 2H),
1.95-2.30 (m, 5H), 3.30 (m, 1H), 3.69 (m, 1H), 3.80 (s, 3H), 4.64
(s, 2H), 6.67 (d, 1H, J=8.0 Hz), 7.00 (d, 1H, J=8.5 Hz), 7.15-7.24
(m, 2H), 7.32 (brs, 1H).
[0690] I-177
[0691] mp: 219-220.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H), 1.75-2.01 (m, 4H),
2.18-2.30 (m, 1H), 2.95-3.15 (m, 2H), 4.61 (s, 2H), 6.56 (m, 1H),
6.80 (d 1H, J=8.5 Hz), 7.16 (m, 2H), 7.28 (brs, 1H), 9.87 (brs,
1H).
[0692] I-178
[0693] mp: 170-173.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.18-1.39 (m, 2H),1.40 (s, 9H), 1.50-1.80 (m, 2H),
1.90-2.33 (m, 5H), 2.36 (s, 6H), 2.75 (t, 2H, J=5.5 Hz), 3.30 (m,
1H), 3.70 (m, 1H), 4.08 (t, 2H, J=5.5 Hz), 6.68 (d, 1H, J=8.0 Hz),
6.94 (d, 11H, J=7.5 Hz), 7.15-7.23 (m, 2H), 7.33 (brs, 1H).
[0694] I-179
[0695] mp: 191-193.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.58-1.80 (m, 2H),
1.98-2.32(m, 5H), 3.30 (m, 1H), 3.70 (d, 1H, J=9.5 Hz), 4.77 (s,
2H), 6.73 (d, 1H, J=8.0 Hz), 7.04 (d, 1H, J=8.0 Hz), 7.20-7.31 (m,
2H), 7.48 (brs, 1H).
[0696] I-180
[0697] mp: 174-176.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.10-1.30 (m, 2H), 1.40 (s, 9H), 1.45-1.65 (m, 2H),
1.81-2.02 (m, 3H), 2.15-2.30 (m, 2H). 2.58 (t, 2H, J=6.5 Hz), 3.25
(m, 1H), 3.37 (dt, 2H, J=5.5, 6.5 Hz), 3.60 (d, 1H, J=9.5 Hz), 3.71
(s, 2H), 5.73 (brs, 1H), 7.20-7.40 (m, 5H).
[0698] I-181
[0699] mp: 176-178.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.70 (m, 6H),
1.85-2.01 (m, 3H), 2.15-2.28 (m, 2H), 2.63 (t, 2H, J=7.0 Hz), 3.25
(dt, 2H, J=6.0, 7.0 Hz), 3.27 (m, 1H), 3.63 (m, 1H), 5.35 (brs,
1H), 7.17 (m, 3H), 7.29 (m, 2H).
[0700] I-182
[0701] mp: 152-154.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.65 (m, 2H),
1.85-2.05(m, 3H), 2.09-2.25 (m, 2H). 3.25 (m 1H), 3.45 (dt, 2H,
J=5.0, 5.0 Hz), 3.55 (t, 2H, J=5.0 Hz), 3.60 (m, 1H), 4.51 (s, 2H),
5.81 (brs, 1H), 7.29-7.40 (m, 5H).
[0702] I-183
[0703] mp: 208-211.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.31(m, 2H), 1.39(s, 9H), 1.62-1.68(m, 2H),
1.98-2.25(m, 5H), 3.30(m, 1H), 3.57(d, 1H, J=9.2 Hz), 4.59(d, 2H ,
J=5.8 Hz), 5.76(brs, 1H), 7.37(dd, 1H, J=8.4, 2.0 Hz), 7.46-7.52(m,
2H), 7.69(brs, 1H), 7.78-7.83(m, 3H).
[0704] I-184
[0705] mp: 180-182.degree. C.
[0706] .sup.1H-NMR (CDCl.sub.3) .delta.ppm:1.22-1.37(m, 2H),
1.40(s, 9H), 1.60-1.69(m, 2H), 2.05-2.09(m, 2H), 2.21-2.27(m, 3H),
3.45(m, 1H), 3.64(d, 1H, J=9.6 Hz), 4.77(d, 2H, J=4.9 Hz), 7.43(d,
1H, J=8.6 Hz), 7.46(brs, 1H), 7.61(t, 1H, J=7.7 Hz), 7.73(t, 1H,
J=7.7 Hz), 7.87(t, 1H, J=7.7 Hz), 8.20(t, 1H, J=7.7 Hz), 8.24(d,
1H, J=8.6 Hz).
[0707] I-185
[0708] mp:260-261.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.22-1.32(m, 2H), 1.39(s, 9H), 1.60-1.70(m, 2H),
1.97-2.01(m, 2H), 2.11(m, 1H), 2.21-2.24(m, 2H), 3.30(m, 1H),
3.61(d, 1H, J=9.3 Hz), 4.95(d, 2H, J=6.0Hz), 5.85(brs, 1H), 7.33(d,
1H, J=4.8 Hz), 7.62(dd, 1H, J=8.4, 6.9 Hz), 7.75(dd, 1H, J=8.1, 6.9
Hz), 8.00(d, 1H, J=8.1 Hz), 8.20(d, 1H, J=8.4 Hz), 8.42(d, 1H,
J=4.8 Hz).
[0709] I-186
[0710] mp: 231-233.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.23-1.40(m, 2H), 1.40(s, 9H), 1.62-1.76(m, 2H),
2.04-2.10(m, 2H), 2.22-2.32(m, 3H), 3.30(m, 1H), 3.95(d, 1H, J=9.3
Hz), 5.04(d, 2H, J=4.1 Hz), 7.61(d, 1H, J=5.8 Hz), 7.63(brs, 1H),
7.65(dd, 1H, J=8.2, 6.9 Hz), 7.73(dd, 1H, J=8.5, 6.9 Hz), 7.86(d,
1H, J=8.2 Hz), 8.10(d, 1H, J=8.5 Hz), 8.42(d, 1H, J=5.8 Hz).
[0711] I-187
[0712] mp: 184-187.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.97(t, 3H, J=7.3 Hz), 1.18-1.30(m, 2H), 1.39(s, 9H),
1.42-1.65(m, 4H), 1.70-1.80(m, 2H), 1.94-2.08(m, 3H), 2.18-2.26(m,
2H), 3.29(m, 1H), 3.61(d, 1H, J=9.5 Hz), 3.93(t, 2H, J=6.4 Hz),
4.39(d, 2H, J=5.5 Hz), 5.67(brs, 1H), 6.79-6.83(m, 3H), 7.23(t, 1H,
J=7.6 Hz).
[0713] I-188
[0714] mp: 224-226.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.16-1.31(m, 2H), 1.38(s, 9H), 1.55-1.70(m, 2H),
1.92-2.07(m, 3H), 2.17-2.23(m, 2H), 3.21(m, 1H), 3.81(s, 3H),
3.83(s, 6H), 4.05(d, 1H, J=9.8 Hz), 4.34(d, 2H, J=5.8 Hz),
5.96(brs, 1H), 6.47(s, 2H).
[0715] I-189
[0716] mp: 217-218.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.15-1.30(m, 2H), 1.37(s, 9H), 1.52-1.66(m, 2H),
1.90-2.06(m, 3H), 2.13-2.20(m, 2H), 2.93(s, 6H), 3.24(m, 1H),
3.94(d, 1H, J=9.5 Hz), 4.30(d, 2H, J=5.5 Hz), 5.73(brs, 1H),
6.69(d, 2H, J=8.9 Hz), 7.12(d, 2H, J=8.9 Hz).
[0717] I-190
[0718] mp: amorphous solid. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.17-1.32(m, 2H), 1.39(s, 9H), 1.54-1.72(m, 2H),
1.96-2.13(m, 3H), 2.18-2.27(m, 2H), 3.30(m, 1H), 3.63(d, 1H, J=9.2
Hz), 4.51(d, 2H, J=5.8 Hz), 5.82(brs, 1H), 7.40(d, 2H, J=8.5 Hz),
8.02(d, 2H, J=8.5 Hz), 8.64(s, 1H).
[0719] I-191
[0720] mp: 126-128.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.97(t, 3H, J=7.4 Hz), 1.10-1.28(m, 2H), 1.36(s, 9H),
1.42-1.86(m, 9H), 2.06-2.18(m, 2H), 3.22(m, 1H), 3.95(t, 2H, J=4.5
Hz), 4.16(brs, 1H), 4.85(s, 2H), 6.82-6.95(m, 3H), 7.26(t, 1H,
J=7.8 Hz), 8.54(brs, 1H).
[0721] I-192
[0722] mp: 178-181.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:0.96(t, 3H, J=7.3 Hz), 1.18-1.52(m, 4H), 1.39(s, 9H),
1.58-1.76(m, 4H), 1.92-2.00(m, 2H), 2.02-2.29(m, 3H), 3.28(m, 1H),
3.78(d, 1H, J=9.5 Hz), 3.89(t, 2H, J=6.6 Hz), 6.00(brs, 1H),
6.78(s, 4H), 7.35(brs, 1H).
[0723] I-193
[0724] mp: 187-188.degree. C. .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD)
.delta.ppm:1.21-1.40(m, 2H), 1.38(s, 9H), 1.52-1.69(m, 2H),
1.90-2.00(m, 2H), 2.02-2.20(m, 3H), 3.22(m, 1H), 3.75(s, 3H),
6.79(s, 4H).
[0725] I-194
[0726] mp: 251-253.degree. C. .sup.1H-NMR (DMSO-d.sub.6)
.delta.ppm:1.27(s, 9H), 1.24-1.50(m, 4H), 1.72-1.83(m, 2H),
1.91-1.99(m, 2H), 2.16(m, 1H), 3.02(m, 1H), 3.82(s, 3H), 6.79(d,
1H, J=8.2 Hz), 7.01(d, 2H, J=8.8 Hz), 7.85(d, 2H, J=8.8 Hz),
9.72(brs, 1H), 8.64(brs, 1H).
[0727] I-195
[0728] mp: 18.3-185.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.22-1.37(m, 2H), 1.40(s, 9H), 1.58-1.75(m, 2H),
2.05-2.10(m, 2H), 2.20-2.30(m, 3H), 3.32(m, 1H), 3.70(s, 2H),
3.73(s, 3H), 6.79(s, 1H), 8.83(brs, 1H).
[0729] I-196
[0730] mp: 185-187.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.44 (t, 6H, J=7.0 Hz),
1.60-1.80 (m, 2H), 1.95-2.35 (m, 5H), 3.30 (m, I1), 3.62 (d, 1H,
J=8.9 Hz), 4.06(q, 2H, J=7.0 Hz), 4.09 (q, 2H, J=7.0 Hz), 6.08 (s,
1H), 7.02 (s, 1H), 7.36 (s, 1H).
[0731] I-197
[0732] mp: 211-213.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.40 (m, 2H), 1.41 (s, 9H), 1.60-1.80 (m, 2H),
2.00-2.36(m, 5H), 2.61 (s, 3H), 3.32 (m, 1H), 3.64 (d, 1H, J=9.2
Hz), 7.28 (s, 1H), 7.43(t, 1H, J=7.5 Hz), 7.69 (d, 1H, J=7.5 Hz),
7.85 (d, 1H, J=7.5 Hz), 8.02 (s, 1H).
[0733] I-198
[0734] mp: 268-269.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm:1.20-1.39 (m, 2H), 1.40 (s 9H), 1.42-2.32 (m, 7H),
2.90-3.10(m, 4H), 3.30 (m, 1H), 3.68 (d, 1H, J=8.8 Hz), 6.59 (s,
1H), 7.18 (d, 1H, J 8.7 Hz), 7.59(d, 1H, J=8.7 Hz), 7.77 (brs,
1H).
[0735] I-199 mp: 221-224.degree. C.
[0736] I-200 mp: 237-240.degree. C.
[0737] I-201 mp: 87-90.degree. C.
[0738] I-202 mp: 222-223.degree. C.
[0739] I-203 mp: 255-257.degree. C.
[0740] I-204 mp: 234-236.degree. C.
[0741] I-205 mp: 208-210.degree. C.
[0742] I-206 mp: 217-218.degree. C.
[0743] I-207 mp: 275-279.degree. C.
[0744] I-208 mp: 248-250.degree. C.
[0745] I-209 mp: 256-258.degree. C.
[0746] I-210 mp: 270-271.degree. C.
[0747] I-211 mp: 219-220.degree. C.
[0748] I-212 mp: 260-261.degree. C.
[0749] I-213 mp: >300.degree. C.
[0750] I-214 mp: 206-207.degree. C. .sup.1H-NMR (CDCl.sub.3)
.delta.ppm: 0.93(t, 3H, J=7.4 Hz), 1.30-1.42(m, 2H), 1.49(d, H,
,=6.9 Hz), 1.53-1.65(m, 2H), 2.61(t, 2H, J=7.7 Hz), 4.15(sept, 1H,
J=6.9 Hz), 7.04(d, 1H, J=8.2 Hz), 7.20(d, 2H, J=8.2 Hz), 7.51(d,
2H, J=8.2 Hz), 7.89(d. 1H, J=8.8 Hz), 8.18(s, 1H), 10.55(s,
1H).
[0751] I-215
[0752] .sup.1H-NMR (CDCl.sub.3) .delta.ppm:0.93(t, 3H, J=7.3 Hz),
1.30-1.41(m, 2H), 1.52-1.63(m, 2H), 1.95(s, 6H), 2.61(t, 2H, J=7.8
Hz), 6.99(brs, 1H), 7.20(d, 2H, J=8.5 Hz), 7.65(d, 2H, J=8.5 Hz),
7.93(dd, 1H, J=8.5, 2.5Hz), 8.28(d, 1H, J=8.5 Hz), 8.55(d, 1H,
J=2.5 Hz), 9.76(brs, 1H).
[0753] Ia-1
[0754] mp 221-224.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.19-1.38 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m, 2H), 2.00-2.31(m,
5H) 3.18 (t, 4H, J=4.8 Hz), 3.21-3.38 (m, 1H), 3.85 (t, 4H, J=4.8
Hz), 6.64-6.32(m, 2H), 7.11 (s, 1H), 7.20 (t, 1H, J=7.8 Hz), 7.45
(s, 1H).
[0755] Ia-3
[0756] mp 87-90.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.37 (d, 6H, J=6.9 Hz), 1.59-1.70(m, 2H),
1.76-1.88 (m, 2H), 2.32-2.42 (m, 4H), 3.11-3.23 (m, 3H), 3.39 (d,
2H, J=10.8 Hz), 3.74-3.86 (m, 2H), 4.34 (t, 1H, J=9.0 Hz), 6.86 (d,
2H, J=9.0 Hz), 7.30 (s, 1H), 7.40(d, 2H, J=9.0 Hz).
[0757] Ia-4
[0758] mp 233-234.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.40 (s, 9H), 1.26-1.37 (m, 2H), 1.62-1.78
(m, 2H), 2.00-2.22 (m, 5H), 2.42 (t, 2H, J=[1.7 Hz), 3.20-3.40 (m,
1H), 3.46(d, 2H, J=10.5 Hz), 3.67 (d, 1H, J=9.3 Hz), 3.72-3.84 (m,
2H), 6.62-6.76 (m, 2H), 7.10(s, 1H), 7.18(t, 1 Hz J=7.8 Hz), 7.42
(s, 1H).
[0759] Ia-5
[0760] mp 125-126.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.40 (s, 9H), 1.59-1.70 (m, 2H), 1.77-1.84
(m, 2H), 2.30-2.46 (m, 4H), 3.24 (q, 2H, J=6.6 Hz), 3.38 (d, 2H,
J=11.7 Hz), 3.74-3.88 (m, 2H), 4.08 (t, 1H, J=5.7 Hz), 6.87 (d, 2H,
J=8.7 Hz), 7.30 (s, 1H), 7.41(d, 2H, J=8.7 Hz).
[0761] Ia-6
[0762] mp 229-230.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.26-1.34 (m, 2H), 1.39 (d, 6H, J=6.9 Hz),
1.61-1.77 (m, 2H), 1.98-1.26 (m, 5H), 2.32-2.46 (m, 2H), 3.15
(quintet, 1H, J=6.6 Hz), 3.22-3.35 (m, 1H), 3.39 (d, 2H, J=11.4
Hz), 3.74-3.92 (m, 2H), 3.88 (d, 1H, J=8.4 Hz), 6.96-6.71 (m, 2H),
7.05 (brs, 1H), 7.39 (d, 2H, J=9.3 Hz).
[0763] Ia-7
[0764] mp 253-254.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.60 (m 4H), 1.27 (s, 9H), 1.77-2.07 (n, 4H), 2.16-2.34(m,
1H), 2.97-3.15 (m, 1H), 6.78 (d, 1H, J=7.2 Hz), 7.01 (t, 1H, J=6.0
Hz), 7.27(t, 2H, J=6.6 Hz), 7.58 (d, 2H, J=7.5 Hz), 9.78 (s,
1H).
[0765] Ia-8
[0766] mp 257-258.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.54 (m, 4H), 1.27 (s, 9H), 1.77-1.88 (m, 2H),1.88-2.00(m,
2H), 2.16-2.34 (m, 1H), 2.23 (s, 3H), 2.92-3.14 (m, 1H), 6.77 (d,
1H, J=8.4 Hz), 7.07(d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.1 Hz), 9.68
(s, 1H).
[0767] Ia-9
[0768] mp 231-232.degree. C. 1H-NMR (CDCl.sub.3) .delta.ppm: 1.21
(t, 3H, J=7.5 Hz), 1.22-1.38 (m, 2H), 1.40 (s, 9H), 1.62-1.78 (m,
2H), 1.98-2.31 (m, 5H), 2.61 (q, 2H, J=7.5 Hz), 3.24-3.38 (m, 1H),
3.70(d, 1H, J=9.9 Hz), 7.11 (s, 1H), 7.14 (d, 2H, J=8.7 Hz), 7.40
(d, 2H. J=8.7 Hz).
[0769] Ia-10
[0770] mp 233-234.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.96 (t, 3H, J=7.2 Hz), 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.56-1.78
(m, 4H), 1.98-2.32 (m, 5H), 2.54 (t, 2H, J=7.2 Hz), 3.23-3.39 (m,
1H), 3.66(d, 1H, J=9.6 Hz), 7.08 (s, 1H), 7.12 (d, 2H, J=8.4 Hz),
7.39 (d.. 21H J=8.4 Hz).
[0771] Ia-11
[0772] mp 243-244.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22 (d, 6H, J=6.9), 1.22-1.77 (m, 4H), 1.40 (s, 9H), 2.01-2.30(m,
5H), 2.83-2.92 (m, 1H), 3.24-3.40 (m, 1H), 3.66-3.69 (m, 1H), 7.09
(s, 1H), 7.17(d, 2H, J=8.4 Hz), 7.41 (d, 2H, J=8.1 Hz).
[0773] Ia-12
[0774] mp 246-247.degree. C. 1H-NMR (CDCl.sub.3) .delta.ppm: 0.80
(t, 3H, J=7.5), 1.20 (d, 3H, J=7.2), 1.26-1.77(m, 6H), 1.40 (s,
9H), 2.01-2.27 (m, 5H), 2.51-2.60 (m, 1H), 3.20-3.38 (m, 1H),
3.64-3.69(m, 1H), 7.08 (s, 1H), 7.12 (d, 2H, J=8.4 Hz), 7.41 (d,
2H, J=8.4 Hz).
[0775] Ia-13
[0776] mp 278-279.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.52 (m, 4H), 1.29 (s, 9H), 1.40 (s, 9H), 1.61-1.77(m, 2H),
2.02-2.30 (m, 5H), 3.20-3.38 (m, 1H), 3.66-3.69 (m, 1H), 7.10 (s,
1H), 7.33(d, 2H, J=9.0 Hz), 7.42 (d, 2H, J=8.7 Hz).
[0777] Ia-14
[0778] mp 263-264.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.51 (m, 4H), 1.27 (s, 9H), 1.82-1.99 (m, 4H), 2.19-2.28(m,
1H), 2.98-3.12 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.33 (d, 2H, J=8.7
Hz), 7.61(d, 2H, J=9.0 Hz), 9.94 (s, 1H).
[0779] Ia-15
[0780] mp 209-210.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.25 (d, 6H, J=6.3 Hz), 1.40 (s, 9H), 1.70-1.98 (m, 8H), 2.19-2.38
(m, 3H), 3.39 (d, 2H, J=11.7 Hz), -3.2 (m, ,H), (m, 1H),
6.82-6.96(m, 2H), 7.10 (br, 1H), 7.41 (d, 2H. J=8.1 Hz).
[0781] Ia-16
[0782] mp 238-240.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.52 (m, 4H), 1.27 (s, 9H), 1.81-1.84 (m, 2H), 1.93-1.97(m,
2H), 2.16-2.23 (m, 1H), 2.95-3.12 (m, 1H), 3.70 (s, 3H), 6.77 (d,
1H, J=8.4 Hz), 6.85(d, 2H, J=9.0 Hz), 7.48(d, 2H, J=9.3 Hz), 9.64
(s, 1H).
[0783] Ia-17
[0784] mp 245-246.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.52 (m, 4H),1.27 (s,9H),1.83-1.87 (m,2H),1.94-1.99(m, 2H),
2.20-2.28 (m, 1H), 2.98-3.12 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.28
(d, 2H, J=8.7 Hz), 7.69 (d, 2H, J=9.0 Hz), 9.64 (s, 1H).
[0785] Ia-18
[0786] mp 240-241.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.78 (m,4H),1.40 (s,9H),2.05-2.33 (m,5H),3.22-3.44(m, 1H),
3.64-3.67 (m, 1H), 6.61 (s, 1H), 6.69-6.77 (m, 2H).
[0787] Ia-19
[0788] mp 240-241.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.24-1.77 (m, 4H), 1.40 (s, 9H), 2.05-2.30 (m, 5H), 3.22-3.38(m,
1H),3.70-3.74 (m, 1H), 7.00-7.15 (m, 3H),7.36 (s, 1H), 8.29-8.31
(m, 1H).
[0789] Ia-20
[0790] mp 239-240.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.24-1.78(m,4H), 1.40(s,9H),2.02-2.30(m, 5H), 3.22-3.40(m, 1H),
3.63-3.66(m, 1H), 6.89-6.84(m, 1H), 7.10-7.17(m, 2H), 7.22-7.34(m,
1H), 7.48-7.51(m, 1H).
[0791] Ia-21
[0792] mp 259-260.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.21 (d, 6H, J=6.0 Hz), 1.22-1.44 (m, 2H), 1.40(s, 9H),
1.60-1.78 (m, 2H), 1.87-2.03 (m, 2H), 2.08-2.29 (m, 3H), 2.39 (t,
2H, J=10.2 Hz), 3.14-3.32(m, 1H), 3.19 (d, 2H, J=11.4 Hz),
3.77-3.93 (m, 2H), 5.33 (d, 1H, J=9.0 Hz), 6.84(dd, 1H, JFH,
HH=8.1, 8.1 Hz), 7.20 (d, 1H, J=7.8 Hz), 7.49 (d, 1H, JFH=14.7 Hz),
8.86 (s, 1H).
[0793] Ia-22
[0794] mp 234-235.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1,20 (d, 6H, J=5.7 Hz), 1.22-1.44 (m, 2H), 1.38 (s, 9H), 1.54-1.76
(m, 2H), 1.94-2.32 (m, 5H), 2.27 (s, 3H), 2.39 (t, 2H, J=10.8 Hz),
2.87(d, 2H, J=11.4 Hz), 3.20-3.40 (m, 1H), 3.76-3.92 (m, 2H), 3.91
(d, 1H, J=9.3 Hz), 6.93 (d, 1H, J=8.1 Hz), 7.21 (brs, 1H), 7.27
(brs, 1H), 7.36 (brs, 1H).
[0795] Ia-23
[0796] mp 195-196.degree. C.
[0797] .sup.1H-NMR (CDCl.sub.3) .delta.ppm: 1.20-1.44 (m, 4H), 1.41
(s, 9H), 1.59-1.76 (m, 2H), 2.03-2.14(m, 2H), 2.16-2.33 (m, 3H),
3.20-3.40 (m, 1H), 3.64 (s, 1H, J=9.0 Hz), 7.19-7.24(m, 1H),
7.44(brs, 1H), 7.52-7.63 (m, 2H), 8.17 (d, 1H, J=8.7 Hz).
[0798] Ia-24
[0799] mp 209-210.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.39 (m, 2H), 1.56 (s, 9H), 1.61-1.78 (m, 2H), 2.00-2.12(m,
2H), 2.17-2.33 (m, 3H), 3.24-3.39 (m, 1H), 3.67 (d, 1H, J=9.6 Hz),
6.90-7.01(m, 1H), 7.21(s, 1H), 7.95-8.06 (m, 1H).
[0800] Ia-25
[0801] mp 278-281.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.10 (d, 6H, J=6.3 Hz), 1.27 (s, 9H), 1.28-1.55 (m, 4H), 1.78-2.00
(m, 4H), 2.11-2.26 (m, 1H), 2.31 (t, 2H, J=11.1 Hz), 3.00-3.10 (m,
1H), 3.08(d, 1H, J=10.8 Hz), 3.67-3.80 (m, 2H), 6.78 (d, 1H, J=8.7
Hz), 7.08 (d, 1H, J=9.0 Hz), 7.41(dd, 1H, J=2.4, 8.7 Hz), 7.78 (d,
1H, J=8.7 Hz), 9.85 (s, 1H).
[0802] Ia-26
[0803] mp 253-255.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.13 (d, 6H, J=6.0 Hz), 1.27 (s, 9H), 1.28-1.52 (m, 4H), 1.78-2.00
(m, 4H), 2.21 (t, 2H, J=11.1 Hz), 2.26-2.36 (m, 1H), 2.96-3.10(m,
1H), 3.56(d, 1H, J=12.3 Hz), 3.60-3.72 (m, 2H), 6.66-6.84 (m, 4H),
7.47 (t, 1H, J=9.3 Hz), 9.28(s, 1H).
[0804] Ia-27
[0805] mp 223-226.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.09 (d, 5H, J=6.3 Hz), 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.77-2.01
(m, 4H), 2.32 (t, 2H, J=11.1 Hz), 2.32-2.42 (m, 1H), 2.90 (d, 1H,
J=11.4 Hz), 2.96-3.12 (m, 1H). 3.76-3.92 (m, 2H), 6.78-6.98 (m,
3H), 7.68 (dd, 1H, J=3.3, 8.7 Hz), 8.84 (s 1H).
[0806] Ia-28
[0807] mp 237-238.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.44 (m, 2H), 1.25 (d, 6H, J=6.3 Hz), 1.40 (s, 9H), 1.61-1.79
(m, 2H), 2.05-2.32 (m, 5H), 2.21 (s, .3H), 2.38 (t, 2H, J=10.2 Hz),
3.22-3.42(m, 1H), 3.40 (d, 2H, J=11.1 Hz), 3.65 (d, 1H, J=9.3 Hz),
3.72-3.90 (m, 2H), 6.70-6.78(m, 2H), 6.81 (brs, 1H), 7.50 (d, 1H,
J=9.6 Hz).
[0808] Ia-29
[0809] mp 208-209.degree. C. 1H-NMR (CDCl.sub.3) .delta.ppm: 1.22
(d, 6H, J=6.0 Hz), 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m,
2H), 2.00-2.16 (m, 2H), 2.14-2.33 (m, 3H), 2.45 (t, 2H, J=11.1 Hz),
3.21(d, 2H, J=10.8 Hz), 3.24-3.38 (m, 1H), 3.63 (d, 1H1, J=9.3 Hz),
3.80-3.94 (m, 2H), 5.33(d, 1H, J=9.0 Hz), 6.66 (dd, 1H, JFH,
HH=6.6, 6.6 Hz), 7.16 (brs, 1H), 7.89 (dd, 1H, JFH, HH=9.0, 9.0
Hz).
[0810] Ia-30
[0811] mp 284-287.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.08 (d, 6H, J=6.0 Hz), 1.26 (s, 9H), 1.28-1.53(m, 4H), 1.82-2.22
(m, 4H), 2.25-(m, 1H), 2.73(t, 2H, J=10.5 Hz), 2.97-3.14 (m, 1H),
3.18(d, 2H, J=11.4 Hz), 3.65-3.76 (m, 2H), 6.79 (d, 1H, J=8.7 Hz),
9.75 (s, 1H).
[0812] Ia-31
[0813] mp 200-201.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.40 (m, 2H), 1.40 (s, 9H), 1.62-1.76 (m, 2H), 2.04-2.32(m,
5H), 3.22-3.40 (m, 1H) 3.62-3.66 (m, 1H), 7.22-7.24 (m, 1H),
7.38-7.38(m, 1H), 7.60(s, 1H), 8.33-8.36 (m, 1H).
[0814] Ia-32
[0815] mp 260-261.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.25-1.42 (m, 2H), 1.38 (s, 9H), 1.64 (q, 2H, J=13.5
Hz), 1.95 (d, 2H, J=12.3 Hz), 2.16 (d, 2H, J=10.5 Hz), 2.18-2.32
(m, 1H), 3.14-3.30 (m, 1H), 5.53 (d, 1H, J=9.0 Hz), 7.31 (d, 1H,
J=8.7 Hz), 7.46 (dd, 1H, J=2.4, 8.7 Hz), 7.90 (d, 1H, J=2.1 Hz),
9.35 (s, 1H).
[0816] Ia-33
[0817] mp 227.degree. C. .sup.1H-NMR(DMSO-d.sub.6) .delta.ppm: 1.27
(s, 9H), 1.30-1.56 (m, 4H), 1.78-2.01 (m, 2H), 2.12-2.36 (m, 2H),
2.96-3.13 (m, 1H), 3.70 (s, 3H), 3.71 (s, 3H), 6.77 (d, 1H, J=8.7
Hz), 6.85 (d, 1H, J=8.7 Hz), 7.06 (dd, 1H, J=2.4, 8.7 Hz), 7.33 (d,
1H, J 2.4 Hz), 9.65 (s, 1H).
[0818] Ia-35
[0819] mp 214-216.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.23-1.38(m, 2H), 1.40(s, 9H), 1.60-1.76 (m, 2H), 2.00-2.12 (m,
2H), 2.20-2.32 (m, 3H), 3.24-3.39 (m, 1H), 3.68 (d, 1H, J=9.0 Hz),
6.77 (d, 1H, J=8.7 Hz), 7.00 (dd 1H, J=2.4, 8.7 Hz), 7.77 (s, 1H),
8.45 (d, 1H, J=2.4 Hz).
[0820] Ia-36
[0821] mp 241-242.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.25-1.42 (m, 2H), 1.37 (s, 9H); 1.62 (q, 2H, J=11.7
Hz), 1.93 (d, 2H, J=12.0 Hz), 2.12 (d, 2H, J=10.8 Hz), 2.16-2.30
(m, 1H), 3.12-3.28 (m, 1H), 3.84 (s, 3H), 6.07 (d, 1H, J=8.4 Hz),
6.89 (dd, 1H, JFH, HH=9.3, 9.3 Hz), 7.24 (d, 1H, J=8.7 Hz), 7.55
(d, 1H, JFH=13.5 Hz), 9.32 (s, 1H).
[0822] Ia-37
[0823] mp 248-249.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.60-0.73 (m, 1H), 0.91 (d, 6H, J=6.6), 1.12-1.40 (m, 2H), 1.40 (s,
9H), 1.54-1.88 (m, 5H), 1.98-2.29 (m, 7H), 3.22-3.37 (m, 1H),
3.51-3.54 (m, 2H), 3.72 (d, 1H, J=9.6), 6.88 (d, 1H, J=8.7), 7.06
(s, 1H), 7.35 (d, 1H, J=9.0).
[0824] Ia-38
[0825] mp 237-238.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.01 (d, 6H, J=6.6), 1.20-1.40 (m, 2H), 1.40 (s, 9H), 1.60-1.74 (m,
4H), 1.99-2.28 (m, 7H), 2.69-2.82 (m, 2H), 3.02-3.14 (m, 2H),
3.20-3.38 (m, 1H), 3.80-3.90 (m, 1H), 6.83-6.86 (m, 2H), 7.14 (s,
1H), 7.34 (d, 1H, J=8.4).
[0826] Ia-39
[0827] mp 234-235.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.20-1.36 (m, 2H), 1..40 (s, 9H), 1.60-1.77 (m, 2H), 1.90-2.32 (m,
5H), 3.21-3.39 (m, 1H), 3.65 (d, 1H, J=9.6 Hz), 6.87 (d, 1H, J=8.7
Hz), 7.04 (s, 1H), 7.37 (dd, 1H, J=2.7, 8.7 Hz), 7.56 (d, 1H, J=2.7
Hz).
[0828] Ia-40
[0829] mp 257-258.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.14 (d, 6H, J=6.0 Hz), 1.27 (s, 9H), 1.28-1.53 (m, 4H), 1.78-2.00
(m, 41H), 2.13-2.256 (m, 1H), 2.30 (t, 2H, J=11.7 Hz), 2.97-3.12
(m, 1H), 3.53-3.67 (m, 2H), 4.01 (d, 1H, J=12.3 Hz), 6.80 (dd, 1H,
J=3.0, 9.0 Hz), 7.79 (d, 1H, J=9.0 Hz), 8.27 (s, 1H), 9.66 (s,
1H).
[0830] Ia-41
[0831] mp 245-246.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.25-1.42 (m, 2H), 1.37 (s, 9H), 1.62 (q, 2H, J=12.6
Hz), 1.94 (d, 2H, J=11.1 Hz), 2.13 (d, 2H, J=11.1 Hz), 2.18-2.35
(m, 1H), 3.11-3.29 (m, 1H). 6.07 (d, 1H, J=8.1 Hz), 6.95-7.06 (in,
1H), 7.14-7.27 (m, 1H), 7.44 (d, 1H, J=7.2 Hz), 7.79 (s, 1H), 9.48
(s, 1H).
[0832] Ia-43
[0833] mp 294-295.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.26 (s, 9H), 1.28-1.53 (m, 4H), 1.76-1.87 (m, 2H), 1.89-2.00 (m,
2H), 2.13-2.25 (m, 1H), 2.96-3.10 (m, 5H), 3.52-3.60 (m, 4H), 6.78
(d, 1H, J=9.0 Hz), 6.88 (d, 2H, J=9.0 Hz), 7.44 (d, 2H, J=9.0 Hz),
9.59 (s, 1H).
[0834] Ia-44
[0835] mp 250-252.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.13 (d, 6H, J=6.3 Hz), 1.21-1.38 (m, 2H), 1.41 (s, 9H), 1.63-1.80
(m, 2H), 1.93 (t, 2H, J=10.8 Hz), 2.00-2.10 (m, 2H), 2.16-2.32 (m,
3H), 3.24-3.39 (m, 1H), 3.54 (d, 2H, J=10.2 Hz), 3.64-3.78 (m, 3H),
7.47 (s, 1H), 7.69 (d, 2H, J=9.0 Hz), 7.73 (d, 2H, J=9.0 Hz).
[0836] Ia-45
[0837] mp 193.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.10 (t, 6H, J=7.2 Hz), 1.26 (s, 9H), 1.28-1.52 (m, 4H), 1.75-1.86
(m, 2H), 1.89-2.01 (m, 2H), 2.10-2.22 (m, 1H), 2.96-3.10 (m, 1H),
3.30-3.52 (m, 12H) 6.60 (d, 2H, J=9.0 Hz), 6.80 (d, 1H, J=9.0 Hz),
7.33 (d, 2H, J=9.0 Hz), 9.46 (s, 1H).
[0838] Ia-46
[0839] mp >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.28 (s, 9H),1.28-1.58 (m,4H),1.83-2.04 (m,4H), 2.23-2.36 (m, 1H),
2.46 (s, 3H), 3.00-3.14 (m, 1H), 6.79 (d, 1H, J=8.7 Hz), 7.34 (d,
1H, J=8.7 Hz), 7.78 (d, 2H, J=8.7 Hz), 7.89 (d, 1H, J=8.4 Hz), 7.91
(s, 1H), 8.00 (d, 2H, J=8.7 Hz), 10.13 (s, 1H).
[0840] Ia-47
[0841] mp 236-237.degree. C. .sup.1H-(CDCL.delta.ppm:(d,6H, J=6.6
Hz),1.01 (d,6H, J=6.6 Hz), 1.20-1.37 (m, 2H), 1.40 (s, 9H),
1.60-1.84 (m, 3H), 1.97-2.31 (m,5H), 2.50 (t, 1H, J=10.8 Hz), 2.78
(dt, 1H, J=3.3, 11.4 Hz), 3.25-3.38 (m, 1H), 3.45 (d, 1, J=11.4
Hz). 3.75 (dt, 1H, J=2.4, 11.4 Hz), 4.02 (dt, 1H, J=2.4, 11.4 Hz),
6.88 (d 2H. J=9.0 Hz), 7.05 (s, 1H), 7.39 (d, 2H, J=9.0 Hz).
[0842] Ia-48
[0843] mp 228-229.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.88 (t, 6H, J=7.2 Hz), 1.19-1.45 (m, 4H), 1.40 (s, 9H), 1.45-1.76
(m, 4H), 1.76-1.92 (m, 1H), 1.96-2.30 (m, 5H), 2.66-3.20 (m, 3H),
3.20-3.40 (m, 1H), 3.78 (d, 1H, J=9.3 Hz), 3.82 (s, 1H), 6.62-6.98
(m, 2H), 7.09 (brs, 1H), 7.37 (d, 2H, J=7.8 Hz).
[0844] Ia-49
[0845] mp 262-263.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.21 (d, 6H, J=5.7 Hz), 1.26-1.34 (m, 2H), 1.37 (d, 6H,
J=5.4 Hz), 1.52-1.76 (m, 2H), 1.85-2.03 (m, 2H), 2.03-2.30 (m, 3H),
2.30-2.53 (m, 2H), 3.02-3.33 (m, 4H), 3.75-3.98 (m, 2H), 5.70 (brs,
1H), 6.73-6.98 (m, 1H), 7.14-7.25 (m, 1H), 7.52 (d, 1H, JFH=13.5
Hz), 8.86 (brs, 1H).
[0846] Ia-50
[0847] mp 232-233.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.21 (d, 6H, J=6.3 Hz), 1.22-1.37 (m, 2H), 1.38 (d, 6H, J=6.9 Hz),
1.68 (q, 2H, J=12.6 Hz), 1.98-2.26 (m, 5H), 2.29 (s, 3H), 2.41 (t,
2H, J=10.2 Hz), 2.88 (d, 2H, J=11.1 Hz), 3.15 (septet, 1H, J=6.6
Hz), 3.21-3.37 (m, 1H), 3.77-3.92 (m, 2H), 3.87 (d, 1H, J=7.8 Hz),
6.88-7.06 (m, 3H), 7.35 (s, 1H).
[0848] Ia-51
[0849] mp 211-212.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.20-1.42 (m, 2H), 1.26 (d. 6H, J=6.3 Hz), 1.38 (d, 6H, J=6.9 Hz),
1.62-1.78 (m, 2H), 1.99-2.28 (m, 5H), 2.49 (dd, 2H, J=10.5, 10.5
Hz), 3.17 (quint, 1H, J=6.9 Hz), 3.20-3.38 (m, 1H), 3.66-3.99 (m,
2H), 3.90-4.01 (m, 3H), 6.62 (d, 1H, J=9.Hz), 7.06 (s, 1H), 7.90
(dd, 1H, J=2.4, 9.0 Hz), 8.09 (d, 1H, J=2.4 Hz).
[0850] Ia-52
[0851] mp 247-249.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.21-1.36 (m, 2H), 1.40 (s, 9H) 1.62-1.7 8 (m, 2H), 1.98-2.32 (m,
5H), 2.55 (t, 4H, J=6.0 Hz), 3.23-3.38 (m, 1H).. 3.55 (t, 4H, J=6.0
Hz), 3.72 (d, 1H, J=9.6 Hz), 6.94 (d, 2H J=9.0 Hz), 7.10 (s, 1H),
7.42 (d, 1H, J=9.0 Hz).
[0852] Ia-53
[0853] mp 234-235.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.38 (m, 2H), 1.41 (s, 9H) 1.64-1.80 (m, 2H), 2.00-2.32 (m,
5H), 3.25-3.40 (m, 1H), 3.73 (d, 1H, J=9.3 Hz), 7.43 (s, 1H), 7.48
(t, 2H, J=7.5 Hz), 7.55-7.66 (m, 3H), 7.68-7.89 (m, 4H).
[0854] Ia-54
[0855] mp 235-236.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.24-1.39 (m, 2H), 1.25 (d, 6H, J=6.3 Hz), 1.39 (d, 6H, J=6.9 Hz),
1.60-1.80 (m, 2H), 2.00-2.28 (m, 5H), 2.21 (s, 3H), 2.38 (t, 2H,
J=10.8 Hz), 3.15 (septet, 1H, J=6.3 Hz), 3.23-3.38 (m, 1H), 3.40
(d, 2H, J=11.7 Hz), 3.72-3.88 (m, 2H), 3.87 (d, 1H, J=9.3 Hz),
6.78-6.86 (m, 3H), 7.50 (d, 1H, J=9.6 Hz).
[0856] Ia-55
[0857] mp 185-186.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.14 (d, 6H, J=6.3 Hz), 1.22-1.38 (m, 2H), 1.41 (s, 9H), 1.62-1.78
(m, 2H), 2.02 (t, 2H, J=10.5 Hz), 2.02-2.10 (m, 2H), 2.16-2.31 (m,
3H), 3.24-3.39 (m, 1H), 3.56 (d, 2H, J=9.3 Hz), 3.63-3.80 (m, :3H),
7.46 (dd, 1H, J=1.5, 8.1 Hz), 7.51 (t, 1H, J=8.1 Hz), 7.63 (s, 1H),
7.81 (t, 1H, J=1.8 Hz), 7.98 (dt, 1H, J=1.8, 8.1 Hz).
[0858] Ia-56
[0859] mp 229-230.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.28-1.54 (m, 4H), 1.38 (s, 6H), 1.78-1.84 (m, 2H),
1.90-2.00 (m, 2H), 2.15-2.30 (m, 1H), 2.97-3.13 (m, 1H), 4.90 (s,
1H), 6.79 (d, 1H, J=9.0 Hz), 7.34 (d, 2H, J=8.7 Hz), 7.48 (d, 2H,
J=8.4 Hz), 9.72 (s, 1H).
[0860] Ia-57
[0861] mp 211-212.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.24-1.40 (m, 2H), 1.38 (s, 9H), 1.57-1.74 (m, 2H),
1.91 (s, 3H), 1.92-2.01 (m, 2H), 2.12-2.24 (m, 2H), 2.51 (brs, 1H),
3.18-3.33 (m, 1H), 4.96 (d, 1H, J=9.3 Hz), 7.16-7.53 (m, 9H), 7.41
(s, 1H).
[0862] Ia-58
[0863] mp 298-299.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.24 (s, 9H), 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.75-2.02 (m, 4H),
2.14-2.28 (m, 1H), 2.97-3.11 (m, 1H), 6.78 (d, 1H, J=8.4 Hz), 7.18
(d, 2H, J=9.0 Hz), 7.48 (d. 2H, J=9.0 Hz), 9.46 (s, 1H), 9.76 (s,
1H).
[0864] Ia-59
[0865] mp 253-254.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.40 (m, 2H), 1.41 (s, 9H), 1.65-1.81 (m, 2H), 2.04-2.16 (m,
2H), 2.22-2.36 (m, 2H), 3.24-3.41 (m, 1H), 3.74 (d, 1H, J=9.6 Hz),
7.40-7.54 (m, 3H), 7.88-8.01 (m, 3H), 8.66 (d, 1H, J=1.5 Hz), 9.57
(d, 1H, J=1.2 Hz).
[0866] Ia-60
[0867] mp 213-214.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.32-1.50 (m, 2H), 1.35 (s, 9H), 1.52-1.70 (m, 2H), 1.88-2.00 (m,
2H), 2.04-2.16 (m, 2H), 2.22-2.38 (m, 1H), 2.65 (s, 3H), 2.99-3.15
(m, 1H, J=9.3 Hz), 7.28 (d, 1H, J=9.0 Hz), 7.81 (s, 1H), 8.20 (s,
1H), 8.47 (s, 1H), 9.89 (s, 1H).
[0868] Ia-61
[0869] mp 274-275.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 1H), 1.28-1.58 (m, 4H), 1.84-2.08 (m, 4H), 2.22-2.40 (m, 1H),
2.99-3.15 (m, 1H), 3.01 (s, 3H), 6.81 (d, 1H, J=8.1 Hz), 7.78 (d,
2H, J=7.8 Hz), 7.84 (d, 2H, J=8.4 Hz), 8.18 (s, 1H), 10.43 (s,
1H).
[0870] Ia-62
[0871] mp 235-236.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22-1.39 (m, 2H), 1.41 (s, 3H), 1.66-1.80 (m, 2H), 2.01-2.12 (m,
2H), 2.14-2.22 (m, 1H), 2.23-2.34 (m, 2H), 3.24-3.42 (m, 1H), 3.69
(d, 1H, J=9.5 Hz), 6.44 (d, 1H, J=9.3 Hz), 7.27 (brs, 1H), 7.28 (d.
1H, J=9.3 Hz), 7.37 (dd, 1H, J=9.0 Hz), 7.68 (d, 1H, J=9.6 Hz),
8.04 (d, 1H, J=2.4 Hz).
[0872] Ia-63
[0873] mp 277-279.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.77-2.02 (m, 4H), 2.15-2.29 (m,
1H), 2.90 (s, 3H), 2.96-3.13 (m, 1H), 6.79 (d, 1H, J=8.7 Hz), 7.12
(d, 2H, J=9.0 Hz), 7.54 (d, 2H, J=9.0 Hz), 9.50 (s, 1H), 9.81 (s,
1H).
[0874] Ia-64
[0875] mp 259-260.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.26 (s, 9H), 1.26-1.50 (m, 4H), 1.71-1.99 (m, 4H), 2.10-2.25 (m,
1H), 2.95-3.10 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 6.97 (d, 2H, J=9.0
Hz), 7.42 (d, 2H, J=9.0 Hz), 7.50-7.71 (m, 5H), 9.73 (s, 1H), 10.05
(s, 1H).
[0876] Ia-65
[0877] mp 292-293.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.62-1.72 (m, 2H), 1.77-1.87 (m,
2H), 1.91-2.10 (m, 4H), 2.13-2.25 (m, 1H), 2.98-3.12 (m, 1H),
3.41-3.52(m, 2H), 5.09 (s, 1H), 6.79 (d, 1H, J=9.0 Hz), 6.91 (d,
2H. J=9.0 Hz), 7.37 (d, 2H, J=9.0 Hz), 7.42 (d, 2H, J=9.0 Hz), 7.51
(d, 2H, J=9.0 Hz), 9.56 (s, 1H).
[0878] Ia-66
[0879] mp >300.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.27(s, 9H), 1.28-1.58 (m, 4H), 1.85-2.02 (m, 4H), 2.40-2.52 (m,
1H), 3.00-3.16 (m, 1H), 6.81 (d, 1H. J=9.0 Hz), 7.50-7.58 (m, 3H),
7.90-7.97 (m, 2H), 12.58 (s, 1H).
[0880] Ia-67
[0881] mp 199-200.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.14 (d, 6H, J=6.3 Hz), 1.28 (s, 9H), 1.31-1.48 (m, 4H), 1.76-1.88
(m, 2H), 2.17 (t, 2H, J=11.1 Hz), 2.82 (t, 2H, J=11.7 Hz), 3.46 (d,
2H, J=11.4 Hz), 3.20-3.36 (m, 1H), 3.62-3.74 (m, 2H), 4.02 (d, 2H,
J=12.9 Hz), 6.83 (d, 2H, J=9.0 Hz), 6.89 (d, 1H, J=8.7 Hz), 7.28
(d, 2H, J=9.0 Hz), 8.27 (s, 1H).
[0882] Ia-68
[0883] mp 237-239.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.40 (s, 9H) 1.49-1.65 (m, 2H), 1.99-2.10 (m, 2H), 2.95
(t, 2H, J=11.1 Hz), 3.36-3.52 (m, 1H), 4.17 (d, 1H, J=12.9 Hz),
5.84 (d, 1H, J=8.7 Hz), 6.39(d, 1H, J=9.6 Hz), 7.21(d, 1H, J=9.3
Hz), 7.51(dd, 1H, J=2.4, 9.3Hz), 7.72 (d, 1H, J=9.9 Hz), 7.85 (d,
1H, J=2.7 Hz), 8.04 (s, 1H).
[0884] Ia-69
[0885] mp 259-260.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.25-1.55 (m, 4H), 1.27 (s, 9H), 1.82-2.05 (m, 4H), 2.22-2.36 (m,
1H), 2.98-3.17 (m, 1H), 4.16 (s, 3H), 6.80 (d. 1H, J=8.4 Hz),
7.77-7.87 (m, 4H), 10.16 (s, 1H).
[0886] Ia-70
[0887] mp 259-260.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s, 9H), 1.36-1.56 (m, 2H), 1.80-1.92 (m, 2H), 2.86-3.02 (m, 2H),
3.36-3.52 (m, 1H), 4.04-4.20 (m, 2H), 6.92 (d, 1H, J=7.5 Hz),
7.38-7.58 (m, 3H), 8.00-8.14 (m, 2H), 8.90 (s, 1H), 9.08 (s, 1H),
9.63 (s, 1H).
[0888] Ia-71
[0889] mp 228-229.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.27-1.42 (m, 2H), 1.38 (s, 9H), 1.57-1.75 (m, 2H),
1.90-2.02 (m, 2H), 2.12-2.34 (m, 3H), 3.14-3.32 (m, 1H), 5.37 (d,
1H, J=9.3 Hz), 7.38-7.43 (m, 33H), 7.46 (d, 2H, J=8.7 Hz),
7.51-7.60 (m, 2H), 7.68 (d, 2H, J=9.0 Hz), 9.33 (s, 1H).
[0890] Ia-75
[0891] mp 169-170.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.58-0.72 (m, 1H), 0.80 (d, 3H, J=6.6 Hz), 0.94 (d, 3H, J=6.0 Hz),
1.14-1.35 (m, 3H), 1.39 (s, 9H), 1.48-1.66 (m, 2H), 1.74-2.06 (m,
5H), 2.06-2.44 (m, 6H) 3.18-3.35 (m, 1H), 3.64-3.74 (m, 1H),
4.46-4.60 (m, 1H), 6.98-7.38 (m, 5H).
[0892] Ia-76
[0893] mp 236-237.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.27-1.42 (m, 2H), 1.38 (d, 6H, J=6.6 Hz), 1.60-1.78
(m, 2H), 1.94-2.06 (m, 2H), 2.12-2.30 (m, 3H), 3.06-3.34 (m, 2H),
5.10 (brs, 1H), 6.41 (d, 1H, J=9.9 Hz), 7.25 (d, 1H, J=8.4 Hz),
7.48 (dd, 1H, J=2.4, 8.7 Hz), 7.68 (d, 1H, J=9.9 Hz), 8.12 (d, 1H,
J=2.4 Hz), 8.88 (brs, 1H).
[0894] Ia-77
[0895] mp 117-118.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.38 (d, 6H, J=6.9 Hz), 1.65 (quintet, 2H, J=5.4 Hz), 1.75-1.91 (m,
2H), 2.42 (t, 2H, J=7.4 Hz), 3.10-3.24 (m, 3H), 4.77 (brs, 1H),
6.41 (d, 1H, J=9.6 Hz), 7.18-7.26 (m, 1H), 7.48 (dd, 1H, J=1.8, 8.7
Hz), 7.67 (d, 1H, J=9.9 Hz), 8.01 (s, 1H), 8.23 (brs, 1H).
[0896] Ia-78
[0897] mp 138-139.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.41 (s, 9H), 1.64 (quintet, 2H, J=6.6 Hz), 1.84 (quintet, 2H,
J=7.3 Hz), 2.42 (t, 2H, J=7.5 Hz), 3.26 (q, 2H, J=6.5 Hz), 4.59
(brs, 1H), 6.41 (d, 1H, J=9.3 Hz), 7.23 (d, 1H, J=8.7 Hz), 7.49
(dd, 1H, J=2.4, 9.0 Hz), 7.67 (d, 1H, J=9.9 Hz), 8.03 (d, 1H, J=2.4
Hz), 8.28 (brs, 1H).
[0898] Ia-79
[0899] mp 289-290.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.63 (m, 4H), 1.28 (s, 9H), 1.84-2.08 (m, 4H), 2.24-2.41 (m,
1H), 3.00-3.16 (m, 1H), 6.82 (d, 1H, J=8.1 Hz), 7.36-7.60 (m, 5H),
7.86-7.99 (m, 2H), 8.28 (s, 1H), 10.50 (s, 1H).
[0900] Ia-80
[0901] mp 239-240.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.22
(d, 1H, J=6.6 Hz), 1.23-1.40 (m, 2H), 1.40-1.59 (m, 2H), 1.40-1.59
(m, 2H), 1.83-2.04 (m, 4H), 2.23-2.39 (m, 1H), 2.98-3.23 (m, 2H),
7.00 (d, 1H, J=7.8 Hz), 7.36-7.59 (m, 5H), 7.85-7.97 (m, 2H), 8.29
(s, 1H), 10.50 (s, 1H).
[0902] Ia-81
[0903] mp 205-206.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.40 (s, 9H), 1.66 (quintet, 2H, J=7.0 Hz), 1.85
(quintet, 2H, J=7.2 Hz), 2.45 (t, 2H, J=7.5 Hz), 3.24 (t, 2H, J=6.5
Hz), 5.17 (brs, 1H), 7.36-7.54 (m, 5H), 7.85 (d, 1H, J=8.4 Hz),
8.07 (dd, 1H, J=1.8, 8.1 Hz), 8.23 (d, 1H, J=1.8 Hz), 9.61 (s,
1H).
[0904] Ia-82
[0905] mp 216-217.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.14 (d, 6H, J=6.3 Hz), 1.22 (d, 6H, J=6.9 Hz), 1.22-1.53 (m, 4H),
1.76-1.98 (m, 2H), 2.21 (t, 2H, J=10.8 Hz), 2.22-2.36 (m, 1H),
2.96-3.20 (m, 2H), 3.57 (d, 2H, J=12.0 Hz), 3.60-3.74 (m, 1H),
6.66-6.85 (m, 2H), 6.98 (d, 1H, J=7.8 Hz), 7.47 (d, 1H, J=8.7 Hz),
9.30 (s, 1H).
[0906] Ia-83
[0907] mp 118-119.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.41 (d, 6H, J=6.3 Hz), 1.26 (s, 9H), 1.40-1.67 (m, 4H), 2.17-2.36
(m, 3H) 2.97-3.10 (m, 2H), 3.57 (d, 2H, J=12.0 Hz), 3.61-3.74 (m,
1H), 6.67-6.92 (m, 3H), 7.48 (t, 1H, J=9.0 Hz), 9.37 (s, 1H).
[0908] Ia-84
[0909] mp 265-267.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.21 (d, 6H, J=6.6 Hz), 1.20-1.57 (m, 4H) 1.60-2.30 (m, 9H),
2.99-3.20 (m, 4H), 3.40-3.52 (m, 2H), 5.09 (s, 1H), 6.91 (d, 2H,
J=8.7 Hz), 6.98 (d, 1H, J=7.5 Hz), 7.37 (d, 2H, J=8.7 Hz), 7.42 (d,
21, J=8.7 Hz), 7.51(d, 2H, J=8.7 Hz), 9.56 (s, 1H).
[0910] Ia-85
[0911] mp 185-186.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.26 (s, 9H), 1.42-1.72 (m, 6H), 1.96-2.10 (m, 2H), 2.26 (t, 2H,
J=6.9 Hz), 2.96-3.12 (m, 4H), 3.41-3.52 (m, 2H), 5.09 (s, 1H), 6.88
(d, 1H, J=8.7 Hz), 6.92 (d, 2H, J=9.0 Hz), 7.37 (d, 2H, J=8.7 Hz),
7.43 (d, 2H, J=9.0 Hz), 7.52 (d, 2H, J=8.7 Hz), 9.63 (s, 1H).
[0912] Ia-86
[0913] mp 162-164.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.21 (d, 6H, J=6.6 Hz), 1.41-1.73 (m, 6H), 1.96-2.10 (m, 2H), 2.26
(t, 2H, J=7.2 Hz), 2.91-3.20 (m, 5H), 3.42-3.52 (m, 2H), 5.09 (s,
1H), 6.92 (d, 2H, J=9.3 Hz), 6.99 (t, 1H, J=6.0 Hz), 7.37 (d, 2H,
J=8.7 Hz), 7.43 (d, 2H, J=9.3 Hz), 7.52 (d, 2H, J=8.7 Hz), 9.64 (s,
1H).
[0914] Ia-87
[0915] mp 245-247.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.22 (d, 6H, J=6.6 Hz), 1.22-1.58 (m, 4H), 1.81-2.02 (m, 4H),
2.22-2.36 (m, 1H), 3.00-3.20 (m, 2H), 3.01 (s, 3H), 6.99 (d, 1H,
J=8.4 Hz), 7.75-7.88 (m, 2H), 8.19 (d, 1H, J=1.2 Hz), 10.43 (s,
1H).
[0916] Ia-88
[0917] mp 208-209.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.22 (d, 6H, J=6.9 Hz), 1.22-1.55 (m, 4H), 1.75-1.98 (m, 4H),
2.11-2.24 (m, 1H), 2.98-3.20 (m, 2H), 5.96 (s, 2H), 6.82 (d, 1H,
J=8.4 Hz), 6.91-7.03 (m, 2H), 7.30 (d, 1H, J=1.8 Hz), 9.72 (s,
1H).
[0918] Ia-89
[0919] mp 142-143.degree. C. 1H-NMR (DMSO-d.sub.6) .delta.ppm: 1.27
(s, 9H), 1.40-1.66 (m, 4H), 2.26 (t, 2H, J=7.5 Hz), 3.02 (q, 2H,
J=6.6 Hz), 5.96 (s, 2H), 6.(d, 1H, J=8.4 H6.88 (t, 1H, J=8.4 Hz),
6.94 (dd, 1H, J=1.8, 8.4 Hz), 7.30 (d, 1H, J=1.8 Hz), 9.78 (s,
1H).
[0920] Ia-90
[0921] mp 100.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.20 (d, 6H, J=6.9 Hz), 1.40-1.66 (m, 4H), 2.26 (t, 2H, J=7.5 Hz),
2.89-2.99 (m, 2H), 3.13 (quint, 1H, J=6.6 Hz), 5.96 (s, 2H), 6.83
(d, 1H, J=8.1 Hz), 6.91-7.02 (m, 2H), 7.30 (d, 1H, J=1.8 Hz), 9.78
(s, 1H).
[0922] Ia-91
[0923] mp 189-190.degree. C. 1H-NMR (DMSO-d.sub.6) .delta.ppm: 1.26
(s,9H),1.43-1.71 (m,4H), 2.40 (t2H, J=7.5 Hz), 2.97-3.09 (m, 2H),
3.01 (s, 3H), 6.85-6.93 (m, 1H), 7.76-7.88 (m, 2H), 8.20 (d, 1H,
J=1.2 Hz), 10.49 (s, 1H).
[0924] Ia-104
[0925] mp 238-241.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.50 (m, 1H), 3.05 (m,
1H), 6.55 (brs, 1H), 6.79 (d, 1H, J=8.2), 7.15 (t, 1H, J=4.8), 8.64
(d, 2H, J=4.8).
[0926] Ia-105
[0927] mp 2:32-234.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(s, 9H), 1.2-1.5.(m, 4H), 1.8-2.0 (m, 4H), 2.55 (m, 1H), 3.05 (m,
1H), 6.77 (d, 1H, J=8.7) 9.92 (s, 2H), 10.93 (s, 1H).
[0928] Ia-106
[0929] mp 226-228.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s,9H),1.22-1.58 (m,4H),1.82-2.04 (m, 1H),2.29 (m, 1H), 3.07 (m,
1H), 6.79 (d, 1H, J=8.7 Hz), 7.61 (dd, 1H, J=1.8 Hz, 8.7 Hz), 8.04
(d, 1H, J=8.7 Hz), 8.48 (d, 1H, 2.1 Hz), 9.35 (s, 1H), 10.05 (s,
1H).
[0930] Ia-107
[0931] mp 282-283.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.57 (m, 4H), 1.27 (s, 9H), 1.80-2.04 (m, 4H), 2.27 (m, 1H),
3.06 (m, 1H), 6.81 (d, 1H, J=8.7 Hz), 7.32 (m, 1H), 7.44 (t, 2H,
J=7.5 Hz), 7.57-7.72 (m, 6H), 9.91 (s, 1H).
[0932] Ia-108
[0933] mp 191-192.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.58 (m, 4H),1.28 (s,9H),1.86-2.04 (m, 4H), 2.70 (m, 1H), 3.08
(m, 1H), 6.83 (d, 1H, J=8.7 Hz), 7.63-7.79 (m, 2H), 8.31 (d, 1H,
J=7.2 Hz), 10.27 (s, 1H).
[0934] Ia-109
[0935] mp 283-285.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.60 (m,4H),1.28 (s,9H),1.87-2.04 (m, 4H),2.42 (m, 1H), 3.09
(m, 1H), 3.87 (s, 2H), 6.82 (d, 1H, J=8.7 Hz), 7.28-7.43 (m, 3H),
7.60 (d, 2H, J=7.8 Hz), 7.68 (d, 1H, J=7.2 Hz), 7.89 (d, 1H, J=7.5
Hz), 9.48 (s, 1H).
[0936] Ia-110
[0937] mp 263-265.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.54 (m,4H),1.27 (s,9H),1.76-1.87 (m,2H),1.89-2.01 (m, 2H),
2.17 (m, 1H), 3.04 (m, 1H), 4.01 (s, 4H), 6.01 (s, 2H), 6.44 (d,
2H, J=8.7 Hz), 6.77 (d, 1H, J=8.7 Hz), 7.39 (d, 2H, J=9.0 Hz), 9.44
(s, 1H).
[0938] Ia-111
[0939] mp 239-241.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.54 (m, 4H), 1.27 (s, 9H), 1.62-1.76 (m, 4H), 1.80-2.02 (m,
4H), 2.30 (m, 1H),2.47-2.59 (m, 2H), 2.66-2.76 (m, 2H), 6.08 (m,
1H), 6.79 (d, 1H, J=9.0Hz), 6.88 (d, 1H, J=6.9 Hz), 7.02 (t, 1H,
J=7.5 Hz), 7.13 (d. 1H, J=7.5 Hz), 8.98 (s, 1H).
[0940] Ia-124
[0941] mp 247-249.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.3 Hz), 1.30 (s, 9H), 2.15-2.26 (m, 2H), 3.48-3.57 (m,
2H), 3.63-3.76 (m, 2H), 6.92 (d, 2H, J=8.7 Hz), 7.59 (d, 2H, J=9.0
Hz), 7.38 (d, 2H, J=9.0 Hz), 7.87 (d, 2H, J=8.7 Hz), 9.92 (brs,
1H), 9.98 (brs, 1H).
[0942] Ia-125
[0943] mp 228-232.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.30
(s, 9H), 1.95-2.08 (m, 2H), 2.77-2.89 (m, 4H), 7.17 (d, 1H, J=8.4
Hz), 7.39 (d, 2H, J=9.0 Hz), 7.42-7.48 (m, 1H), 7.64 (brs, 1H),
7.87 (d, 2H, J=9.0 Hz), 9.99 (brs, 2H).
[0944] Ia-126
[0945] mp 244-246.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 7.42 (d, 2H, J=8.4 Hz), 7.81 (dd, 1H, J=2.1 Hz, 8.7 Hz),
7.93 (d, 2H, J=9.0 Hz), 8.05 (d, 1H, J=9.0 Hz), 8.66 (d, 1H, J=2.1
Hz), 9.29 (s, 1H), 10.05 (brs, 1H), 10.39 (brs, 1H).
[0946] Ia-127
[0947] mp 238-239.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.30
(s, 9H), 4.18-4.27 (m, 4H), 6.81 (d, 1H, J=8.4 Hz), 7.16 (d-d, 1H,
J=2.7 Hz, 9.0 Hz), 7.34-7.42 (m, 3H), 7.85 (d, 2H, J=8.4 Hz), 9.94
(brs, 1H), 9.99 (brs, 1H).
[0948] Ia-128
[0949] mp 286-287.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s,9H),7.41 (d, 2H, J=8.7 Hz),7.71 (d, 2H, J=8.4 Hz), 7.91 (d, 2H,
J=8.7 Hz), 7.99 (d, 2H, J=8.7 Hz), 10.05 (brs, 1H), 10.44 (brs,
1H).
[0950] Ia-129
[0951] mp 232-234.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.25 (1H, m), 3.07 (m,
1H), 6.80 (d, 1H, J=9.0), 7.37 (d, 1H, J=8.1), 7.53 (t. 1H, J=8.1),
7.75 (t, 1H, J=8.1), 8.12 ( s, 1H), 10.16 (s, 1H).
[0952] Ia-130
[0953] mp 274-27 C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27 (s, 9H),
1.23-1.58 (m, 4H), 1.81-2.03 (m, 4H), 2.28 (m, 1H), 3.07 (m, 1H),
6.80 (d, 1H, J=8.4 Hz), 7.36 (d-d, 1H, J=0.9 Hz, 5.7 Hz), 7.43
(d-d, 1H, J=2.1 Hz, 8.7 Hz), 7.60 (d, 1H, J=5.4 Hz), 7.78 (d, 1H,
J=8.7 Hz), 8.40 (d, 1H, 1.8 Hz), 9.97 (brs, 1H).
[0954] Ia-131
[0955] mp 259-260.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 7.40 (d, 1H, J=4.8 Hz), 7.41 (d, 2H, J=8.7 Hz), 7.66 (d,
1H, J=5.1 Hz), 7.67 (d-d, 1H, J=1.8 Hz, 8.7 Hz), 7.84 (d, 1H, J=9.0
Hz), 7.92 (d, 2H, J=8.7 Hz), 8.50 (s, 1H), 10,03 (brs, 1H), 10,27
(brs 1H).
[0956] Ia-132
[0957] mp 26.5-266.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.17
(d, 6H, J=6.6 Hz), 1.31 (s, 9H), 4.10 (m, 1H), 7.35-7.46 (m, 3H),
7.54 (d, 1H, J=7.5 Hz), 7.87-7.97 (m, 3H), 8.15 (brs, 1H), 8.20 (d,
1H, J=7.5 Hz), 10.03 (brs, 1H), 10.25 (brs, 1H).
[0958] Ia-133
[0959] mp 249-250.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 7.41 (d, 2H, J=8.7 Hz), 7.45 (d, 1H, J=5.4 Hz), 7.67 (d-d,
1H, J=1.8 Hz, 8.7 Hz), 7.76 (d, 1H, J=5.4 Hz), 7.92 (d, 2H, J=8.7
Hz), 7.95 (d, 1H, J=8.1 Hz), 8.39 (d, 1H, J=1.8 Hz), 10.02 (brs,
1H), 10.23 (brs, 1H).
[0960] Ia-134
[0961] mp 305-306.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.25
(m, 2H), 1.25 (s, 9H), 1.52 (m, 2H), 1.82 (m, 2H), 1.94 (m, 2H),
2.13 (m, 1H), 3.04 (m, 1H), 6.00 (d, 1H, J=8.1), 6.74 (d, 1H,
J=8.4), 7.3-7.5 (m, 6H), 7.85 (d, 2H, J=7.5), 8.31 (d, 1H,
J=8.4).
[0962] Ia-135
[0963] mp 220-222.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.37 (m, 1H), 3.03 (m,
1H), 6.80 (d, 1H, J=8.7), 7.04 (m, 1H), 7.29 (m, 1H), 7.79 (m, 1H),
9.60 (s, 1H).
[0964] Ia-136
[0965] mp 26:3-264.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.20(m, 1H), 3.03 (m,
1H), 6.80 (d, 1H, J=8.4), 6.87 (m, 1H), 7.31 (m, 2H), 10.21 (s,
1H).
[0966] Ia-137
[0967] mp 260-262.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.30 (m, 1H), 3.05 (m,
1H), 6.80 (d, 1H, J=8.4), 7.13 (t, 2H, J=8.1), 7.31 (m, 1H), 9.52
(s, 1H).
[0968] Ia-138
[0969] mp 270-273.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.12 (m, 1H), 3.05 (m,
1H), 6.79 (d, 1H, J=9.0), 7.31 (m, 2H), 7.80 (m, 1H), 10.05 (s,
1H).
[0970] Ia-139
[0971] mp 267-270.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.30
(s, 9H), 4.05 (s, 4H), 6.04 (s, 2H), 6.51 (d, 2H, J=8.7 Hz), 7.34
(d, 2H, J=8.4 Hz), 7.54 (d, 2H, J=8.4 Hz), 7.87 (d, 2H, J=8.4 Hz),
9.82 (brs, 1H), 9.97 (brs, 1H).
[0972] Ia-140
[0973] mp 227-229.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.22
(d, 6H, J=6.6 Hz), 1.20-1.57 (m 4H), 1.80-2.01 (m, 4H), 2.27 (m,
1H), 2.95-3.22 (m, 2H), 6.99 (d, 1H, J=7.8 Hz), 7.65 (d, 2H, J=8.7
Hz), 7.80 (d, 2H, J=8.4 Hz), 10.18 (brs, 1H).
[0974] Ia-141
[0975] mp 205-207.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.22
(d, 6H, J=6.9 Hz), 1.20-1.55 (m, 4H), 1.75-2.05 (m, 6H), 2.21 (m,
1H), 2.72-2.85 (m, 4H), 2.93-3.20 (m, 2H), 6.98 (d, 1H, J=8.1 Hz),
7.10 (d, 1H, J=8.1 Hz), 7.26 (d-d, 1H, J=2.1 Hz, 8.1 Hz), 7.51 (s,
1H), 9.67 (brs, 1H).
[0976] Ia-142
[0977] mp 295-296.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.6), 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H),
2.27 (m, 1H), 3.05 (m, 1H), 4.07 (m, 1H), 6.80 (d, 1H, J=8.7), 7.64
(d, 2H, J=8.7), 7.79 (d, 2H, J=8.7), 8.06 (d, 1H, J=7.5), 10.01 (s,
1H).
[0978] Ia-143
[0979] mp 146-147.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(s, 9H), 1.5-1.7 (m, 4H), 2.36 (t, 2H, J=7.8), 3.03 (q, 2H, J=6.3),
6.89 (t, 1H, J=6.3), 7.66 (d, 2H, J=8.4), 7.80 (d, 2H, J=8.4),
10.25 (s, 1H).
[0980] Ia-144
[0981] mp 138-140.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.21
(d, 6H, J=6.0), 1.4-1.7 (m,4H), 2.37 (t, 2H, J=7.5), 2.96 (q, 2H,
J=6.3), 3.14 (m, 1H), 6.99 (t, 1H, J=5.4), 7.66 (d, 2H, J=7.8),
7.81 (d, 2H, J=7.8), 10.26 (s, 1H).
[0982] Ia-145
[0983] mp 134-1.36.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(s, 9H), 1.39 (m, 2H), 1.4-1.7 (m, 4H), 2.28 (t, 2H, J=7.2), 2.79
(m, 4H), 3.02 (q, 2H, J=7.2), 6.88 (t, 1H, J=6.0), 7.10 (t, 1H,
J=6.0), 7.51 (s, 1H), 9.73 (s, 1H).
[0984] Ia-146
[0985] mp 135-137.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.20
(d, 6H, J=6.6), 1.4-1.7 (m, 4H), 1.99 (m, 2H), 2.28 (t, 2H, J=7.2),
2.79 (m, 4H), 2.94 (q, 2H, J=6.3), 3.13 (m, 1H), 6.98 (t, 1H,
J=6.9), 7.10 (d, 2H, J=8.1), 7.26 (d, 2H, J=8.1), 7.51 (s, 1H),
9.73 (s, 1H).
[0986] Ia-147
[0987] mp 20 207.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.29 (s,
9H), 4.54 (d, 2H, J=5.7 Hz), 7.35 (d, 2H, J=9.0 Hz), 7.52 (d, 2H,
J=7.8 Hz), 7.69 (d, 2H, J=8.1 Hz), 7.83 (d, 2H, J=8.7 Hz), 9.02 (t,
1H, J=5.7 Hz), 9.97 (brs, 1H).
[0988] Ia-148
[0989] mp 250-251.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.30(s,9H), 7.18(t, 2H, J=9.3 Hz), 7.40 (d, 2H, J=8.7 Hz), 7.76
(d-d, 2H, J=5.1 Hz, 9.3 Hz), 7.88 (d, 2H, J=9.0 Hz), 10.02 (brs,
1H), 10.17 (brs, 1H).
[0990] Ia-149
[0991] mp 220-222.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.30
(s, 9H), 3.74 (s, 3H), 6.92 (d, 2H, J=9.0 Hz), 7.38 (d, 2H, J=9.0
Hz), 7.64 (d, 2H, J=9.0 Hz), 7.87 (d, 2H, J=9.0 Hz), 9.99 (s,
2H).
[0992] Ia-150
[0993] mp 264-266.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 1.66-1.76 (m, 4H), 2.57-2.66 (m, 2H), 2.71-2.80 (m, 2H),
6.98 (m, 1H), 7.06-7.16 (m, 2H), 7.38 (d, 2H, J=9.0 Hz), 7.90 (d,
2H, J=8.7 Hz), 9.60 (s. 1H), 9.99 (s, 1H).
[0994] Ia-151
[0995] mp 235-236.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.03-1.39 (m, 5H), 1.27 (s 9H), 1.55-1.87 (m, 5H), 3.73 (m, 1H),
7.31 (d, 2H, J=8.7 Hz), 7.76 (d, 2H, J=8.4 Hz), 8.01 (d, 1H, J=7.8
Hz), 9.90 (s, 1H).
[0996] Ia-152
[0997] mp 244-246.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
0.50-0.72 (m, 4H), 1.27 (s, 9H), 2.81 (m, 1H), 7.31 (d, 2H, J=8.7
Hz), 7.73 (d, 2H, J=8.7 Hz), 8.30 (d, 1H, J=4.2 Hz), 9.91 (brs,
1H).
[0998] Ia-153
[0999] mp >300.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.06
(m, 6H), 1.27 (s, 9H), 1.2-1.5 (m, 4,), 1.8-2.0 (m, 4H), 2.25 (m,
1H), 2.7 (m, 1H), 3.05 (m, 1H), 3.51 (m, 4H), 4.30 (m, 1H), 6.80
(d, 1H, J=8.4), 7.34 (d, 2H, J=8.4), 7.65 (d, 2H, J=8.4), 10.01 (s,
1H).
[1000] Ia-154
[1001] mp 247-249.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.05
(m,6H), 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.23 (m,
1H), 2.77 (m, 1H), 3.05 (m, 1H), 3.52 (m, 4H), 4.33 (m, 1H), 6.80
(d, 1H, J=9.0), 7.03 (d, 1H, J=7.8), 7.35 (t, 1H, J=7.8), 7.59 (d,
1H, J=7.8), 7.68 (s, 1H), 9.96 (s, 1H).
[1002] Ia-155
[1003] mp 258-259.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.25(m,
2H), 1.50 (m,2H), 1.86 (m, 2H), 1.99 (m, 2H), 2.28 (m, 1H), 2.93
(s, 3H), 3.10 (m, 1H), 7.02 (d, 1H, J=7.5), 7.65 (d, 2H, J=8.4),
7.80 (d, 2H, J=8.4). 10.20 (s, 1H).
[1004] Ia-156
[1005] mp 250-253.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(m, 2H), 1.50 (m, 2H), 1.82 (m, 2H), 2.00 (m, 4H), 2.22 (m, 1H),
2.79 (m, 4H), 2.92 (s, 3H), 3.11 (m, 1H), 7.01 (d, 1H, J=8.1), 7.26
(d, 1H, J=8.1), 7.51 (s, 1H), 9.68 (s, 1H).
[1006] Ia-157
[1007] mp 259-262.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.13
(d, 6H, J=6.0), 1.25 (m, 2H), 1.50 (m, 2H), 1.80 (m, 2H), 1.95 (m,
2H), 2.17 (m, 3H), 2.92 (s, 3H), 3.10 (m, 1H), 3.70 (m, 2H), 3.68
(m, 2H), 6.86 (d, 2H J=9.3), 7.00 (d, 1H, J=7.2), 7.43 (d, 2H,
J=9.3), 9.58 (s, 1H).
[1008] Ia-158
[1009] mp 298-300.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s,9H),7.30-7.50 (m,5H), 7.63-7.71 (m,4H), 7.87 (d, 2H, J=8.7 Hz),
7.91 (d, 2H, J=9.0 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).
[1010] Ia-169
[1011] mp 278-281.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
0.74-1.87 (m, 20H), 1.29 (s, 9H), 3.76 (m, 1H), 7.32 (d, 2H, J=8.4
Hz), 7.75 (d, 2H, J=8.7 Hz), 7.5 (d, 1H, J=8.7 Hz), 7.90 (brs,
1H).
[1012] Ia-160
[1013] mp 227-228.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.55 (m,4H), 1.27 (s, 9H),1.80-2.02 (m,4H),2.23 (m, 1H), 3.06
(m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.4.5 (t, 1H J=9.9 Hz), 7.82 (m,
1H), 8.12 (d-d, 1H, J=2.4 Hz, 6.3 Hz), 10.17 (brs, 1H).
[1014] Ia-161
[1015] mp 259-260.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.54 (m, 4H), 1.27 (s, 9H), 1.78-2.01 (m, 4H), 2.16 (s, 3H),
2.21 (m, 1H), 3.05 (m, 1H), 6.77 (d, 1H, J=8.4 Hz), 7.12-7.21 (m,
2H), 7.53 (m, 1H), 9.90 brs, 1H).
[1016] Ia-162
[1017] mp 222-226.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.3 Hz), 1.26 (d, 6H, J=6.9 Hz), 2.16-2.26 (m, 2H), 3.31
(m, 1H), 3.48-3.58 (m, 2H), 3.63-3.76 (m, 2H), 6.92 (d, 2H, J=9.0
H), 7.32 (d, 2H, J=8.7 Hz), 7.59 (d, 2H, 9.0 Hz), 7.89 (d, 2H,
J=9.0 Hz), 9.92 (s, 1H), 10.13 (brs, 1H).
[1018] Ia-163
[1019] mp 197-200.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(d, 6H, J=6.3 Hz), 1.95-2.09 (m, 2H), 2.77-2.90 (m, 4H), 3.32 (m,
1H), 7.17 (d, 1H, J=8.1 Hz), 7.32 (d, 2H, J=8.7 Hz), 7.45 (d-d, 1H,
J=1.8 Hz, 8.1 Hz), 7.64 (brs, 1H), 7.90 (d, 2H, J=8.7 Hz), 9.99
(brs, 1H), 10.13 (brs, 1H).
[1020] Ia-164
[1021] mp 145-247.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-2.0 (m, 16H), 2.19 (m, 1H), 3.05 (m, 1H), 4.74 (m,
1H), 6.79 (d, 1H, J=9.0), 6.80 (d, 2H, J=9.0), 7.47 (d, 2H, J=9.0),
9/63 (s, 1H).
[1022] Ia-165
[1023] mp >300.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.03-2.02 (m, 18H): 1.27 (s, 9H), 2.26 (m, 1H), 3.06 (m, 1H), 3.73
(m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.63 (d, 2H, J=9.0 Hz), 7.78 (d,
2H, J=8.7 Hz), 8.02 (d, 1H, J=8.1 Hz). 10.00 (brs, 1H).
[1024] Ia-166
[1025] mp 200-201.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.03-2.02 (m, 18H),1.27 (s, 9H), 2.25 (m, 1H), 3.06 (m, 1H), 3.73
(m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.33 (t, 1H, J=8.1 Hz), 7.46 (d,
1H, J=8.1 Hz), 7.76 (m, 1H), 7.94 (m, 1H), 8.14 (d, 1H, J=8.1 Hz),
9.92 (brs, 1H).
[1026] Ia-167
[1027] mp 282-285.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.57 (m,4H),1.27 (s,9H),1.87-2.03 (m,4H), 2.49 (m, 1H), 3.07
(m, 1H), 6.83 (d, 1H, J=8.7 Hz), 13.20 (brs, 1H).
[1028] Ia-168
[1029] mp 120-124.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
0.94-1.66 (m,14H),1.27 (s,9H),1.80-2.04 (m, 4H), 2.25 (m1H), 2.92
(m, 1H), 3.06 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.42-7.53 (m, 2H),
7.63 (d, 1H, J=7.2 Hz), 7.73 (m, 1H), 8.17 (m, 1H), 10.11 (brs,
1H).
[1030] Ia-169
[1031] mp 256-257.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
0.93-1.20 (m,5H),1.24-1.64 (m, 9H),1.27 (s, 9H), 1.80-2.02 (m, 4H),
2.27 (m, 1H), 2.87 (m, 1H), 3.06 (m, 1H), 6.79 (d, 1H, J=9.0 Hz),
7.48 (d, 1H, J=7.2 Hz), 7.68-7.79 (m, 4H), 10.17 (brs, 1H).
[1032] Ia-171
[1033] mp 242-244.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(m, 12H); 1.45 (m, 4H), 1.90 (m, 4H) 2.(m, 1H), 3.07 (m, 1H) 3.67
(m, 2H), 6.77(d, 1H, J=8.7), 6.90 (d, 1H, J=7.8 1J=7.5), 7.53 (d,
1H, J=7.8) 7.59 (s, 1H), 9.89 (s, 1H).
[1034] Ia-172
[1035] mp >310.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(m, 12H), 1.38 (m, 4H), 1.84 (m, 2H), 1.97 (m, 2H), 2.25 (m 1H),
3.07 (m, 1H) 3.66 (m, 2H), 6.81 (d, 1H, J=8.7), 7.20 (d, 2H,
J=6.7), 7.61 (d, 2H, J=8.7), 9.94 (s, 1H).
[1036] Ia-173
[1037] mp 279-281.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.83 (m, 6H),1.93 (m, 2H), 2.21 (m, 1H),
2.36 (m, 2H), 3.05 (m, 1H), 3.54 (m, 2H), 6.79 (d, 1H, J=8.7), 7.16
(d, 2H, J=9.0), 7.56 (d, 2H, J=9.0), 9.83 (s, 1H).
[1038] Ia-174
[1039] mp 258-262.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.29
(m, 2H), 0.53 (m,2H), 1.20 (m, 1H) 1.27 (s, 9H), 1.3-1.5 (m, 4H),
1.7-2.0 (m, 4H), 2.20 (m, 1H), 3.05 (m, 1H), 3.75 (d, 2H, J=6.9),
6/79 (d, 1H, J=9.0),
[1040] Ia-175
[1041] mp 246-248.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-2.0 (m, 18H), 2.19 (m, 1H), 3.04 (m, 1H), 4.23 (m,
1H), 6.79 (d, 1H, J=8.7), 6.84 (d, 2H, J=9.0), 7.45 (d, 2H, J=9.0),
9.64 (s, 1H).
[1042] Ia-176
[1043] mp 200-202.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-2.0 (m, 18H), 2.21 (m, 1H), 3.05 (m, 1H), 4.23 (m, 1H)
6.57 (d, 1H, J=6.9), 6.80 (d, 1H, J=9.0), 7.0-7.2 (m, 2H), 7.28 (s,
1H), 9.74 (s, 1H).
[1044] Ia-177
[1045] mp 266-268.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.56 (m, 4H), 1.27 (s, 9H), 1.79-2.02 (m, 4H), 2.25 (m, 1H),
3.05 (m, 1H), 6.56 (m, 1H), 6.77-6.84 (m, 2H), 7.58-7.71 (m, 5H),
9.92 (brs, 1H).
[1046] Ia-178
[1047] mp 223-224.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.26-1.54 (m,4H), 1.27 (s, 9H), 1.81-2.02 (m,4H), 2.45 (m, 1H),
3.06 (m, 1H), 6.80 (d, 1H, J=8.7 Hz), 8.15 (d-d, 1H, J=2.4 Hz, 9.0
Hz), 8.27 (d, 1H, J=9.0 Hz), 8.70 (m, 1H), 10.85 (brs, 1H).
[1048] Ia-179
[1049] mp 224-227.degree. C. .sup.1H-NMR (DMSO)
.delta.ppm:1.24-1.56(m,4H)- ,1.27(s, 9H),1.80-2.03(m,4H),2.27(m,
1H), 3.06 (m, 1H), 6.80 (d, 1H, J=8.7 Hz), 6.90 (d, 1H, J=1.8 Hz),
7.72-7.84 (m, 4H), 8.60 (d, 1H, J=1.8 Hz), 10.09 (brs, 1H).
[1050] Ia-180
[1051] mp 226-227.degree. C. .sup.1H-NMR (DMSO)
.delta.ppm:0.92(d,6H,J=6.6 Hz),1.26-1.55(m,4H),1.27(s,9H),1.80-2.03
(m, 4H), 2.27 (m, 1H), 3.05 (m, 1H), 3.20 (m, 1H), 6.80 (d, 1H,
J=8.7 Hz), 7.42 (d, 1H, J=7.2 Hz), 7.67-7.79 (m, 4H), 10.19 (brs,
1H).
[1052] Ia-181
[1053] mp 191-192.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.95
(d, 6H, J=6.6 Hz), 1.26-1.55 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m,
4H), 2.25 (m, 1H), 3.06 (m, 1H), 3.23 (m, 1H), 6.80 (d, 1H,J=8.4
Hz), 7.41-7.53 (m, 2H), 7.58(d, 1H, J=7.2 Hz), 7.73 (m, 11H), 8.18
(m, 1H), 10.13 (brs, 1H).
[1054] Ia-182
[1055] mp 192-193.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.30
(m, 2H), 0.55 (m, 2H), 1.2-1.5 (m, 5H), 1.27 (s, 1H), 1.8-2.0 (m,
4H), 2.20 (m, 1H), 3.04 (m, 1H), 3.75 (d, 2H, J=6.9), 6.58 (m, 1H),
6.79 (d, 1H, J=8.7), 7.0-7.2 (m, 2H), 7.31 (s, 1H), 9.76 (s,
1H).
[1056] Ia-183
[1057] mp >310.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m,4H), 1.82 (m, 2H), 1.97 (m, 2H), 2.04 (m, 2H),
2.39 (m, 1H), 2.46 (t, 2H, J=7.8), 3.07 (m, 1H), 3.79 (t, 2H,
J=7.5), 6.79 (d, 1H, J=8.7), 7.56 (m, 4H), 9.80 (s, 1H).
[1058] Ia-184
[1059] mp 281-283.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.57 (m,4H),1.27 (s,9H),1.80-2.04 (m,4H),2.27 (m, 1H), 3.06
(m, 1H), 6.80 (d, 1H, J=9.0 Hz), 7.33 (s, 1H), 7.75 (d, 2H, J=9.3
Hz), 7.91 (d, 2H, J=8.7 Hz), 8.16 (s, 1H), 10.09 (brs, 1H).
[1060] Ia-185
[1061] mp 226-227.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.24-1.58 (m, 10H),1.27 (s,9H),1.81-2.02 (m,4H),2.28 (m, 1H),
2.78-2.88 (m, 4H), 3.06 (m, 1H), 6.80 (d, 1H, J=8.7 Hz), 7.64 (d,
2H, J=8.7 Hz), 7.82 (d, 2H, J=8.7 Hz), 10.25 (brs, 1H).
[1062] Ia-186
[1063] mp 148-150.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.25-1.60 (m, 10H), 1.27 (s, 9H), 1.82-2.03 (m, 4H), 2.24 (m, 1H),
2.82-2.92 (m, 4H), 3.06 (m, 1H), 6.79 (d, 1H, J=8.4 Hz), 7.36 (m,
1H), 7.55 (t, 1H, J=7.8 Hz), 7.84 (m, 1H), 8.06 (m, 1H), 10.18 brs,
1H).
[1064] Ia-187
[1065] mp >310.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.36 (s, 9H), 1.43 (m,4H), 1.85 (m, 2H), 1.93 (m, 2H),
2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J=8.7), 7.58 (s, 1H), 7.62
(d, 2H, J=9.0), 10.00 (s, 1H).
[1066] Ia-188
[1067] mp 285-292.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.85
(t, 3H, J=7.5), 1.11 (d, 3H, J=6.3), 1.26 (s, 9H), 1.3-1.6 (m, 6H),
1.85 (m, 2H), 1.95 (m, 2H), 2.27 (m, 1H), 3.06 (m, 1H), 3.90 (m,
1H), 6.80 (d, 1H, J=8.4), 7.64 (d, 2H, J=8.7), 7.79 (d, 2H, J=8.7),
7.99 (d, 1H, J=8.1), 10.02 (s, 1H).
[1068] Ia-189
[1069] mp 278-281.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.2-2.0 (m, 17H), 2.03 (m, 2H), 3.03 (m, 1H), 6.79 (d, 1H,
J=8.4), 7.1-7.3 (m, 3H), 7.94 (s, 1H), 9.78 (m, 2H).
[1070] Ia-190
[1071] mp >310.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.1-2.0
(m, 17H), 1.27 (s, 9H), 2.25 (m, 2H), 3.03 (m, 1H), 6.79 (d, 1H,
J=8.7), 7.48 (m, 4H), 9.71 (m, 2H).
[1072] Ia-191
[1073] mp 275-277.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.16
(d, 6H, J=6.6 Hz), 1.31 (s, 9H), 4.09 (m, 1H), 7.41 (d, 2H, J=8.7
Hz), 7.84 (s, 4H), 7.90 (d, 2H, J=9.0 Hz), 8.11 (d, 1H, J=7.5 Hz),
10.04 (brs, 1H), 10.30 (brs, 1H).
[1074] Ia- 192
[1075] mp 204-205.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.6 Hz), 1.20-1.56 (m, 4H), 1.22 (d, 6H, J=6.6 Hz),
1.78-2.00 (m, 4H), 2.25 (m, 1H), 2.98-3.22) (m, 2H), 4.06 (m, 1H),
6.99 (d, 1H, J=8.1 Hz), 7.34 (t, 1H, J=8.1 Hz), 7.46 (d, 1H, J=7.8
Hz), 7.75 (m 1H), 7.96 (m, 1H), 8.17 (d, 1H, J=8.7 Hz), 9.94 (brs,
1H).
[1076] Ia-193
[1077] mp 285-286.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.6 Hz), 1.20-1.56 (m, 4H), 1.22 (d, 6H, J=6.9 Hz),
1.79-2.00 (m. 4H), 2.26 (m, 1H), 2.97-3.20 (m, 2H), 4.07 (m, 1H),
6.99 (d, 1H, J=7.8 Hz), 7.64 (d, 2H, J=8.7 Hz), 7.79 (d, 2H, J=8.7
Hz), 8.06 (d, 1H, J=7.5 Hz), 10.02 (brs, 1H).
[1078] Ia-194
[1079] mp 248-250.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.57(m, 4H), 1.22 (d, 6H, J=6.6 Hz), 1.78-2.00(m, 4H), 2.25
(m, 1H), 2.98-3.22 (m, 2H), 6.56 (m, 1H), 6.82 (d, 1H, J=3.3 Hz),
6.99 (d, 1H, J=7.8 Hz), 7.58-7.71 (m, 5H), 9.92 (brs, 1H).
[1080] Ia-195
[1081] mp 271-275.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s,9H),1.28-1.56 (m, 4H),1.80-2.02 (m,4H),2.25 (m, 1H), 3.06 (m,
1H), 6.80 (d, 1H, J=9.0 Hz), 7.57 (s, 1H), 7.62-7.74 (m, 4H), 8.39
(s, 1H), 9.99 (brs, 1H).
[1082] Ia-196
[1083] mp 226-228.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.30 (m, 2H),1.23 (d,6H, J=6.9),1.2-2.0 (m, 4H), 2.20 (m, 1H), 3.10
(m, 2H), 3.76 (d, 2H, J=6.9), 6.83 (d, 2H, J=8.7), 6.99 (d, 1H,
J=8.1), 7.46 (d, 2H, J=8.7), 9.65 (s, 1H).
[1084] Ia-197
[1085] mp 17:3-175.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:0.31
(m, 2H), 0.56 (m, 2H), 1.22 (d, 6H, J=6.6), 1.2-1.5 (m, 4H),
1.8-2.0 (m, 4H), 2.22 (m, 1H), 3.10 (m, 1H), 3.76 (d, 1H, J=7.2),
6.58 (d, 1H, J=8.1), 7.0-7.2 (m, 2H), 7.32 (s, 1H), 9.78 (s,
1H).
[1086] Ia-198
[1087] mp 233-235.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.25
(d, 6H, J=6.9), 1.2-2.0 (m, 16H), 2.19 (m, 1H), 3.10 (m, 2H), 4.73
(m, 1H), 6.80 (d, 2H, J=8.7), 6.98 (d, 1H, J=7.8), 7.45 (d, 2H,
J=8.7), 9.63 (s, 1H).
[1088] Ia-199
[1089] mp 185-186.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.22
(d, 6H, J=6.9)1.2-2.0 (m, 16H), 2.22 (m, 1H), 3.10 (m, 2H), 4.73
(m, 1H), 6.54 (m, 1H), 7.0-7.2 ((m, 2H), 7.3 (s, 1H), 9.75 (s,
1H).
[1090] Ia-200
[1091] mp 235-237.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.2 (s,
9H), 1.3-1.6 (m, 6H), 1.8-2.0 (m, 6H) 2.20 (m, 1H), 3.05 (m, 1H),
3.45 (m, 2H), 3.82 (m, 2H), 4.47 (m, 1H), 6.79 (t, 1H, J=9.0), 6.89
(d, 2H, J=9.0), 7.47 (d, 2H, J=9.0), 9.66 (s, 1H).
[1092] Ia-201
[1093] mp:300-301.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.6 Hz), 1.26-1.56 (m, 4H), 1.27 (s, 9H), 1.82-2.03 (m,
4H), 2.23 (s, 3H), 2.37 (m, 1H), 3.06 (m, 1H), 4.07 (m, 1H), 6.81
(d, 1H, J=8.7 Hz), 7.52 (d, 1H, J=8.4 Hz), 7.62 (d, 1H, J=8.4 Hz),
7.68 (s, 1H), 8.09 (d, 1H, J=7.5 Hz), 9.22 (brs, 1H).
[1094] Ia-202
[1095] mp 269-270.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.25-1.26 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.25 (m, 1H),
3.07 (m, 1H), 6.80 (d, 1H, J=8.4 Hz), 7.11 (m, 1H), 7.42 (d, 1H,
J=3.6 Hz), 7.48 (m, 1H), 7.58 (d, 2H, J=8.7 Hz), 7.64 (d, 2H, J=8.4
Hz), 9.92 (brs, 1H).
[1096] Ia-203
[1097] mp 271-273.degree. C. .sup.1H-NMR (DMSO)
.delta.ppm:1.14-1.54(m,9H)- ,1.26(s,9H),1.63-1.88(m, 7H),1.89-2.01
(m, 2H), 2.21 (m, 1H), 2.42 (m, 1H), 3.04 (m, 1H), 6.79 (d, 1H,
J=9.0 Hz), 7.11 (d, 2H, J=8.4 Hz), 7.47 (d, 2H, J=8.1 Hz), 9.70
(brs, 1H).
[1098] Ia-204
[1099] mp 250-251.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.22-1.39 (m,2H), 1.22 (d, 6H, J=6.6 Hz), 1.40-1.57(m, 2H),
1.80-2.01 (m, 4H), 2.28 (m, 1H), 2.98-3.(m, 2H), 7.00 (d, 1H, J=7.8
Hz), 7.34 (s, 1H), 7.75 (d, 2H, J=9.0 Hz) 7.91(d, 2H, J=8.7 Hz),
8.17 (s, 1H), 10.10 (brs, 1H).
[1100] Ia-205
[1101] mp 239-240.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27(s,
9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 5H), 2.08 (m, 2H), 3.05 (m, 1H),
3.80 (m, 4H), 4.95 (m, 1H), 6.79 (d, 1H, J=8.7) 6.83 (d, 2H,
J=8.7), 7.48 (d, 2H, J=8.7), 9.66 (s, 1H).
[1102] Ia-206
[1103] mp 236-238.degree. C. .sup.1H-NMR (DMSO)
.delta.ppm:1.27(s,9H), 1.2-1.7 (m,8H),1.8-2.0(m,6H),2.18(m,1H),
3.04 (m, 1H), 3.3-3.6(m, 2H), 3.85 (m, 3H), 6.80 (d, 1H, J=9.0),
6.84 (d, 2H, J=9.0), 7.47 (d, 2H, J=9.0), 9.65 (s, 1H).
[1104] Ia-207
[1105] mp 224-226.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.24(m, 1H), 2.39 (m,
2H), 3.06 (m, 1H), 3.50 (t, 2H, J=7.5), 3.70 (t, 2H, J=6.3), 6.78
(d, 1H, J=6.6), 6.83 (m, 1H), 7.25 (m, 1H), 7.27 (m, 1H), 7.54
(s,1H), 9.61 (s, 1H).
[1106] Ia-208
[1107] mp 275-277.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.22 (m, 1H), 2.38 (m,
2H), 3.07 (m, 1H), 3.47 (t, 2H, J=6.9), 3.69 (t, 2H, J=6.6), 6.80
(d, 1H, J=8.7), 7.14 (d, 2H, J=8.4), 7.58 (d, 2H, J=8.4), 9.83 (s,
1H).
[1108] Ia-209
[1109] mp 214-215.degree. C. .sup.1H-NMR (DMSO)
.delta.ppm:1.26-1.56(m,4H)- ,1.27 (s,9H),1.80-2.03(m,
4H),2.25(m,1H), 3.06 (m, 1H), 6.59 (m, 1H), 6.81 (d, 1H, J=8.4 Hz),
6.86 (d,1 H, J=2.7 Hz), 7.28-7.40 (m, 2H), 7.47 (m, 1H), 7.75 (s,
1H), 8.01 (s, 1H), 9.91 (brs, 1H).
[1110] Ia-210
[1111] mp 272-275.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 6.59 (m, 1H), 6.87 (d, 1H, J=3.3 Hz), 7.41 (d, 2H, J=8.7
Hz), 7.68 (d, 2H, J=8.7 Hz), 7.72 (m, 1H), 7.83 (d, 2H, J=8.7 Hz),
7.90 (d, 2H, J=8.7 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).
[1112] Ia-211
[1113] mp 251-255.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 7.36 (d, 1H), 71 :.6 Hz, 5J=8.4 Hz), 7.91 (d, 2H, J=8.4
Hz), 7.92-8.00 (m, 4H), 8.19 (s, 3H), 10.06 (brs, 1H), 10.38 (brs,
1H).
[1114] Ia-212
[1115] mp 241-244.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.30
(s, 9H), 1.50-1.78 (m, 6H), 1.81-1.97 (m, 2H), 4.78 (m, 1H), 6.87
(d, 2H, J=9.0 Hz), 7.38 (d, 2H, J=8.7 Hz), 7.61 (d, 2H, J=9.0 Hz),
7.87 (d, 2H, J=8.7 Hz), 9.97 (brs, 1H), 9.99 (brs, 1H).
[1116] Ia-213
[1117] mp 283-286.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.31
(s, 9H), 7.12 (d-d, 1H, J=3.6 Hz, 5.1 Hz), 7.41 (d, 2H, J=9.0 Hz),
7.46 (m, 1H), 7.50 (d-d, 2H, J=1.2 Hz, 5.1 Hz), 7.64 (d, 2H, J=8.7
Hz), 7.82 (d, 2H, J=8.7 Hz), 7.90 (d, 2H, J=9.3 Hz), 10.03 (brs,
1H), 10.22 (brs, 1H).
[1118] Ia-213
[1119] mp 224-225.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.22 (d, 6H, J=6.9), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.45 (m,
1H), 3.12 (m, 2H), 6.99 (d, 1H, J=8.1), 8.15 (m, 1H), 8.27 (d, 1H,
J=9.0), 8.69 (s, 1H), 10.86 (s, 1H).
[1120] Ia-219
[1121] mp 270-272.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s, 9H), 1.34-1.51 (m, 2H), 1.80-1.92 (m, 2H), 2.83-2.97 (m, 2H),
3.32 (m, 1H), 3.99-4.12 (m 2H), 6.92 (d, 1H, J=8.7 Hz), 7.57 (d,
2H, J=8.7 Hz), 7.68 (d, 2H, J=9.0 Hz), 8.90 (brs, 1H).
[1122] Ia-220
[1123] mp 187-189.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s, 9H), 1.31-1.51 (m, 2H), 1.78-1.90 (m, 2H), 2.78-2.93 (m, 2H),
3.30 (m, 1H), 3.97-4.09 (m, 2H), 6.90 (d, 1H, J=8.7 Hz), 7.06 (t,
2H, J=9.0 Hz), 7.44 (d-d, 2H, J=4.8 Hz, 9.0 Hz), 8.53 (brs,
1H).
[1124] Ia-221
[1125] mp 260-262.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.12-1.50(m, 7H), 1.63-1.90(s, 9H), 1.63-1.90 (m,7H), 2.40 (m, 1H),
2.76-2.91 (m, 2H), 3.28 (m, 1H), 3.96-4.09 (m, 2H), 6.90 (d, 1H,
J=8.7 Hz), 7.06 (d, 2H, J=8.4 Hz), 7.32 (d, 2H, J=8.4 Hz), 8.40
(brs, 1H).
[1126] Ia-222
[1127] mp 265-267.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.23
(d, 6H, J=6.6 Hz), 1.31-1.48 (m, 2H), 1.77-1.90 (m, 2H), 2.84-2.98
(m, 2H), 3.16 (m, 1H), 3.33 (m, 1H), 3.96-4.10 (m, 2H), 7.11 (d,
1H, J=7.8 Hz), 7.57 (d, 2H, J=8.7 Hz), 7.67 (d, 2H, J=8.4 Hz), 8.90
(brs, 1H).
[1128] Ia-223
[1129] mp 183-186.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.23
(d, 6H, J=6.9 Hz), 1.28-1.47 (m, 2H), 1.76-1.88 (m, 2H), 2.80-3.16
(m, 2H), 3.16 (m, 1H), 3.32 (m, 1H), 3.94-4.07 (m, 2H), 7.00-7.14
(m, 3H), 7.44 (d-d. 2H, J=4.8 Hz, 9.0 Hz), 8.53 (brs, 1H).
[1130] Ia-224
[1131] mp 232-234.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.12-1.46 (m, 7H), 1.23 (d, 6H, J=6.6 Hz), 1.63-1.87 (m, 7H), 2.40
(m, 1H), 2.78-2.93 (m, 2H), 3.15 (m, 1H), 3.31 (m, 1H), 3.94-4.07
(m, 2H), 7.06 (d, 2H, J=8.4 Hz), 7.09 (d, 1H, J=8.1 Hz), 7.32 (d,
2H, J=8.4 Hz), 8.39 (brs, 1H).
[1132] mp 222-224.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s, 9H), 1.30-1.61 (m, 4H), 1.77-1.98 (m, 4H), 2.66-2.90 (m, 2H),
3.28 (m, 1H), 3.40-3.50 (m, 2H), 3.79-3.88 (m, 2H), 3.96-4.08 (m,
2H), 4.44 (m, 1H), 6.85 (d, 2H, J=9.0 Hz), 6.91 (d, 1H, J=9.0 Hz),
7.31 (d, 2H, J=9.3 Hz), 8.34 (brs, 1H).
[1133] Ia-226
[1134] mp 194-195.degree. C. .sup.1H-NMR (CDCl.sub.3/DMSO)
.delta.ppm: 1.39 (d, 6H, J=7.2 Hz), 1.66 (quintet, 2H, J=6.8 Hz),
1.87 (quintet, 2H, J=7.7 Hz), 2.47 (t, 2H, J=7.5 Hz), 3.11-3.22 (m,
1H), 3.21 (t, 2H, J=6.2 Hz), 5.00 (brs, 1H), 7.35-7.56 (m, 5H),
7.86 (d, 1H, J=8.4 Hz), 8.05 (dd, 1H, J=1.8, 8.1 Hz), 8.20 (d, 1H,
J=1.8 Hz), 9.24 (s, 1H).
[1135] Ia-227
[1136] mp >300.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.22
(d, 6H, J=6.3 Hz), 1.20-1.40 (m, 4H), 1.74-2.10 (m, 4H), 2.20-2.40
(m, 1H), 2.39 (s, 3H), 3.00-3.30 (m, 2H), 6.25 (s, 1H), 6.99 (brs,
1H), 7.43-7.57 (m, 1H), 7.71 (d, 1H, J=8.1 Hz), 7.76 (s, 1H), 10.27
(s, 1H).
[1137] Ia-228
[1138] mp 168-169.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(s, 9H), 1.49 (quintet, 2H, J=7.5 Hz), 1.64 (quintet, 2H, J=7.4
Hz), 2.38 (t, 2H, J=7.2 Hz), 2.40 (s, 3H), 3.04 (q, 2H, J=6.5 Hz),
6.25 (s, 1H), 6.89 (t, 1H, J=6.0 Hz), 7.48 (dd, 1H, J=1.8, 8.4 Hz),
7.71 (d, 1H, J=8.4 Hz), 7.77 (d, 1H, J=1.8 Hz), 10.33 (s, 1H).
[1139] Ia-229
[1140] mp 174-175.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.21
(d, 6H, J=6.6 Hz), 1.42-1.56 (m, 2H), 1.56-1.70 (m, 2H), 2.33-2.42
(m, 2H), 2.40 (s, 3H), 2.90-3.02 (m, 2H), 3.14 (septet, 1H, J=6.5
Hz), 6.26 (s, 1H), 6.99 (brs, 1H), 7.48 (d, 1H, J=8.4 Hz), 7.71 (d,
1H, J=8.7 Hz), 7.77 (s, 1H).
[1141] Ia-230
[1142] mp 194-195.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.86
(d, 6H, J=6.9 Hz), 1.25-1.65 (m, 4H), 1.27 (s, 9H), 1.81-2.05 (m,
5H) 2.23-2.35 (m, 1H), 2.99-3.15 (m, 1H), 3.36 (d, 1H, J=7.2 Hz),
6.80 (d, 1H, J=8.4 Hz), 7.80 (d, 1H, J=8.4 Hz), 7.87 (d, 1H, J=8.4
Hz), 8.19 (s, 1H) 10.44 (s, 1H).
[1143] Ia-231
[1144] mp 221-222.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 0.86
(d, 6H, J=6.9 Hz), 1.22-1.40 (m, 2H), 1.23 (d, 6H, J=6.9 Hz),
1.40-1.58 (m, 2H), 1.82-2.04 (m, 5H), 2.22-2.37 (m, 1H), 3.00-3.16
(m, 1H), 3.15 (septet, 1H, J=6.6 Hz), 3.36 (d, 2H, J=7.5 Hz), 6.99
(d, 1H, J=7.5 Hz), 7.80 (d, 1H, J=8.4 Hz), 7.86 (d, 1H, J=8.4 Hz),
8.19 (s, 1H), 10.15 (s, 1H).
[1145] Ia-232
[1146] mp 196-197.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
0.93 (d, 6H, J=6.6 Hz), 1.42 (s, 1H), 1.60-1.70 (m, 2H), 1.88
(quintet, 2H, J=7.4 Hz), 2.02-2.20 (m, 1H), 2.46 (t, 2H, J=7.7 Hz),
3.29 (q, 2H, J=6.1 Hz), 3.48 (d, 2H, J=7.8 Hz), 4.26 (t, 1H, J=6.0
Hz), 7.76 (d, 1H, J=8.1 Hz), 7.90 (dd, 1H, J=1.8, 8.1 Hz), 8.07 (d,
1H, J=1.5 Hz), 8.39 (s, 1H).
[1147] Ia-233
[1148] p. 151-152.degree. C. .sup.1-H-NMR (CDCl.sub.3) .delta.ppm:
0.93 (d, 6H, J=6.6 Hz), 1.40 (d, 6H, J=6.6 Hz), 1.62-1.69 (m, 2H),
1.88 (quintet, 2H, J=7.3 Hz), 2.03-2.16 (m, 1H), 2.47 (t, 2H, J=7.5
Hz), 3.21 (septet, 1H, J=6.8 Hz), 3.23 (q, 2H, J=6.3 Hz), 3.48 (d,
2H, J=7.5 Hz), 4.43 (t, 1H, J=6.0 Hz), 7.76 (d, 1H, J=8.4 Hz), 7.91
(dd, 1H, J=1.8, 8.1 Hz), 8.06 (d, 1H, J=1.8 Hz), 8.36 (s, 1H).
[1149] Ia-234
[1150] mp 219-220.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.28 (s, 9H), 1.30-1.50 (m, 2H), 1.74-1.88 (m, 2H), 2.83 (t, 2H,
J=11.1 Hz), 3.20-3.32 (m, 1H), 3.94-4.07 (m, 2H), 5.94 (s, 2H),
6.77 (d, 1H, J=8.8 Hz), 6.82 (dd, 1H, J=1.8, 8.7 Hz), 6.89 (d, 1H,
J=8.7 Hz), 7.11 (d, 1H, J=1.8 Hz), 8.38 (s, 1H).
[1151] Ia-235
[1152] mp 280-282.degree. C. .sup.1H-NMR (DMSO-d.sub.6) .delta.ppm:
1.27 (s, 9H), 1.26-1.57 (m, 4H), 1.86-2.03 (m, 4H), 2.38-2.50 (m,
1H), 3.00-3.14 (m, 1H), 6.81 (d, 1H, J=8.4 Hz), 7.29 (t, 1H, J=8.4
Hz), 7.43 (t, 1H, J=7.5 Hz), 7.73 (d, 1H, J=8.4 Hz), 7.96 (d, 1H,
J=7.5 Hz), 12.27 (s, 1H).
[1153] Ia-237
[1154] mp 204-205.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.23
(d, 6H, J=6.6 Hz), 1.29-1.61 (m, 4H), 1.75-1.98 (m, 4H), 2.78-2.92
(m, 2H), 3.15 (m, 1H), 3.29 (m, 1H), 3.38-3.51 (m, 2H), 3.78-3.89
(m, 2H), 3.94-4.06 (m, 2H), 4.44 (m, 1H), 6.85 (d, 2H, J=9.0 Hz),
7.10 (d, 1H, J=7.8 Hz), 7.31 (d, 2H, J=9.3 Hz), 8.34 (brs, 1H).
[1155] Ia-238
[1156] mp 128-130.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.26
(s, 9H), 1.41-1.53 (m, 2H), 1.55-1.68 (m, 2H), 2.44 (t, 2H, J=7.2
Hz), 2.98-3.07 (m, 2H), 6.90 (t, 1H, J=6.0 Hz), 8.16 (d-d, 1H,
J=2.1 Hz, 8.7 Hz), 8.29 (d, 1H, J=8.7 Hz), 8.70 (m, 1H), 10.91
(brs, 1H).
[1157] Ia-239
[1158] mp 256-258.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.26-1.53 (m, 4H), 1.26 (s, 9H), 1.76-2.00 (m, 4H), 2.23 (s, 3H),
2.39 (m, 1H), 3.04 (m, 1H), 6.80 (d, 1H, J=8.7 Hz), 7.57 (d-d, 1H,
J=2.4 Hz), 7.97 (d, 1H, J=8.4 Hz), 8.12 (m, 1H), 10.26 (brs,
1H).
[1159] Ia-240
[1160] mp 288-290.degree. C. .sup.1H-NMR (DMSO) .delta.ppm:
1.26-1.53 (m, 4H), 1.27 (s, 9H), 1.78-1.90 (m, 4H), 2.40 (m, 1H),
3.04 (m, 1H), 6.81 (d, 1H, J=8.7 Hz), 7.07 (m, 1H), 7.75 (m, 1H),
8.07 (d, 1H, J=8.4 Hz), 8.29 (m, 1H), 10.36 (brs, 1H).
[1161] Ia-247
[1162] mp 249-250.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.28
(s, 9H), 1.34-1.50 (m, 2H), 1.79-1.90 (m, 2H), 2.74-2.98 (m, 2H),
3.32 (m, 1H), 4.02-4.14 (m, 2H), 6.91 (d, 1H, J=8.4 Hz), 7.94 (d,
1H, J=9.0 Hz), 8.04 (d-d, 1H, J=2.1 Hz, 9.0 Hz), 8.60 (s, 1H), 9.76
(brs, 1H).
[1163] Ia-242
[1164] mp 250-252.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.24
(s, 9H), 1.27 (s, 9H), 1.24-1.54 (m, 4H), 1.76-1.88 (m, 2H),
1.90-2.01 (m, 2H), 2.21 (m, 1H), 3.05 (m, 1H), 6.79 (d, 1H, J=8.7
Hz), 6.88 (d, 2H, J=9.0 Hz), 7:48 (d, 2H, J=9.0 Hz), 9.72 brs,
1H).
[1165] 136-0290
[1166] mp 250-2,52.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.15
(d, 6H, J=6.6 Hz), 1.28 (s, 9H), 1.35-1.52 (m, 2H), 1.78-1.92 (m,
2H), 2.20 (s, 3H), 2.81-2.96 (m, 2H), 3.33 (m, 1H), 3.96-4.16 (m,
3H), 6.92 (d, 1H, J=8.7 Hz), 7.27 (d, 1H, J=8.1 Hz), 7.60 (m, 1H),
7.66 (m, 1H), 8.06 (d, 1H, J=7.8 Hz), 8.14 brs, 1H).
[1167] Ia-244
[1168] mp 211-213.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.29
(s,9H),1.35-1.52 (m,2H),1.81-1.93 (m,2H),2.83-2.97 (m, 2H), 3.32
(m, 1H), 4.03-4.14 (m, 2H), 6.93 (d, 1H, J=8.7 Hz), 7.55 (d-d, 1H,
J=2.1 Hz, 9.0 Hz), 7.94 (d, 1H, J=9.0 Hz), 8.29 (d, 1H, J=1.8 Hz),
8.78 (brs, 1H), 9.19 (s, 1H).
[1169] Ia-245
[1170] mp 196-197.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.2-1.6 (m, 611), 1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m,
1H), 3.73 (m, 4H), 4.99 (s, 1H), 6.79 (d, 1H, J=8.7), 7.13 (d, 1H,
J=6.8), 7.22 (t, 1H, J=6.8), 7.49 (d, 1H, J=6.8), 7.72 (s, 1H),
9.78 (s, 1H).
[1171] Ia-246
[1172] mp 242-244.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.2-1.5 (m, 4H), 1.65 (m, 4H), 1.8-2.0 (m, 4H), 2.23 (m,
1H), 2.71 (m, 1H), 3.06 (m, 1H), 3.43 (m, 2H), 3.93 (m, 2H), 6.79
(d, 1H, J=8.7), 6.91 (d, 1H, J=8.7), 7.20 (t, 1H, J=7.5), 7.40 (d,
1H, J=7.5), 7.53 (s, 1H), 9.76 (s, 1H).
[1173] Ia-247
[1174] mp 242-245.degree. C. .sup.1H-NMR (DMSO) .delta.ppm: 1.27
(s, 9H), 1.2-1.6 (m, 6H), 1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m,
1H), 3.74 (m, 4H), 4.94 (brs, 1H), 6.79 (d, 1H, J=8.7), 7.38 (d 1H,
J=8.7), 7.52 (d, 1H, J=8.7), 9.76 (s, 1H).
[1175] Ia-248
[1176] mp 272-274.degree. C. .sup.1H-NMR (CDCl.sub.3) .delta.ppm:
1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.62 (m, 4H), 1.8-2.0 (m, 4H), 2.22
(m, 1H), 2.68 (m, 1H), 3.05 (m, 1H), 3.41 (m, 2H), 3.92 (m, 2H),
6.79 (d, 1H, J=9.0), 7.15 (d, 2H, J=8.7), 7.50 (d, 2H, J=8.7),
9.73(s, 1H).
[1177] Ia-249 mp 174-176.degree. C.
[1178] Ia-250 mp 255-257.degree. C.
[1179] Ia-252 mp 249-251.degree. C.
[1180] Ia-253 mp 120-121.degree. C.
[1181] Ia-254 mp 236-237.degree. C.
[1182] Ia-255 mp 172-174.degree. C.
[1183] Ia-256 mp 257-259.degree. C.
[1184] Ia-257 mp 179-180.degree. C.
[1185] Ia-258 mp 227-229.degree. C.
[1186] Ia-259 mp 135-136.degree. C.
[1187] Experiment 1 Affinity for NPY Y5 Receptor
[1188] cDNA sequence encoding a human NPY Y5 receptor (WO96/16542)
was cloned in the expression vector pME18S (Takebe et al. Mol.
Cell. Biol. 8, 8957). The obtained expression vector was
transfected into a host CHO cells by using a Lipofect AMINE reagent
(Trademark, Gico BRL Co., Ltd.) according to an instruction
protocol to obtain the cells that stably express NPY Y5
receptor.
[1189] The membranes prepared from the above CHO cells expressing
NPY Y5 receptor, the compound of the present invention and 30,000
cpm [.sup.125I] peptide YY (60 pM of final concentration: Amersham)
were incubated in the assay buffer (20 mM HEPES-Hanks buffer
containing 0.1% bovine serum albumin, pH 7.4) at 25.degree. C. for
2 hours and then the maxture was filtered with a glassfilter GF/C
treated with polyethyleneimine. After the glassfilter was washed
with 50 mM Tris-HCl buffer (pH 7.4), the radioactivity on the
filter was measured with a gamma counter. The non-specific binding
was detected in the presence of 200 nM of peptide YY. The 50 %
inhibitory concentration of the test compound against the specific
peptide YY binding (IC.sub.50 value) was calculated (Inui, A. et
al. Endocrinology 131, 2090-2096 (1992)). The results are shown in
Tables 1 and 2.
[1190] The compounds of the present invention inhibited the binding
of peptide YY (NPY homologue) to NPY Y5 receptors. In other words,
the compounds of the present invention showed affinity for the NPY
Y5 receptor.
[1191] Experiment 2 cAMP Production Inhibitory Activity in CHO
Cells
[1192] After CHO cells expressing human NPY Y5 receptor were
incubated in the presence of 2.5 mM isobutylinethylxanthine (SIGMA)
at 37.degree. C. for 20 min, the compound of the present invention
was added and incubated for 5 min. Then, 50 nM NPY and 10 .mu.M
forskolin (SIGMA) were added to the cells and incubated for 30 min.
After the reaction was terminated by adding 1N HCl, the amount of
cAMP in the supernatant was measured with EIA kit (Amersham LIFE
SCIENCE). The inhibitory activity of NPY against forskolin
stimulated cAMP was regarded as 100% and the 50% inhibitory
concentration (IC.sub.50 value) of the compound of the present
invention against the NPY activity was calculated. The results are
shown in Tables 1 to 4.
1 TABLE 1 binding cAMP Compound IC.sub.50(nM) IC.sub.50(nM) I-2 7.5
72 I-7 3 <10 I-11 1.3 5 I-18 4.4 29 I-20 7 21 I-22 8.6 51 I-24
9.6 71 I-25 0.6 2.6 I-41 5.3 38.2 I-44 1.0 13.4 I-45 1.2 27.9 I-46
0.8 10.5 I-47 0.6 14.9 I-49 0.4 8.1 I-50 0.3 8.4 I-53 4.1 21 I-55
9.0 40 I-57 4.8 47 I-59 0.8 35 I-60 0.69 18 I-61 0.26 5.3 I-62 0.58
16 I-63 1.3 50 I-64 2.2 80 I-65 1.8 72 I-66 1.5 30 I-67 2 17 I-69
3.8 13 I-72 2.3 2.1 I-75 0.55 3.4 I-76 0.61 5.5 I-77 1.8 28 I-79
0.59 25 I-83 0.61 29 I-84 1.3 25 I-86 3.4 100 I-87 0.66 21 I-90 2.8
50 I-92 7 61 I-101 3.9 38 I-102 1.7 14 I-106 6.4 29
[1193]
2 TABLE 2 I-109 1.2 3.2 I-110 4.3 13.6 I-111 1.8 6.1 I-114 7 30
I-116 1.2 11 I-120 1.4 4.8 I-123 1.8 168 I-126 0.6 13.2 I-127 1.4
30.4 I-128 1.3 10.2 I-129 2.1 174 I-130 1.1 42.5 I-131 1.1 34.8
I-132 2.2 30.4 I-133 0.9 21.1 I-134 0.5 10.0 I-135 0.7 22.0 I-136
2.8 -- I-137 1.4 68.2 I-138 1.0 18.6 I-139 0.41 7.6 I-140 0.48 8.9
I-141 0.42 7.4 I-142 0.49 28 I-143 3.5 44 I-144 3.4 52 I-146 2.3 20
I-147 7.1 63 I-149 0.83 15 I-150 0.17 5.2 I-151 0.17 2.6 I-152 0.88
46 I-153 1.7 29 I-154 1.1 11 I-156 0.81 17 I-160 0.61 8.8 I-161
0.49 3.1 I-162 1.7 32 I-163 2.3 83 I-164 0.71 5.9 I-165 0.44 47
I-166 0.37 9.7 I-167 0.72 39 I-168 2.1 32 I-171 2.4 71 I-172 0.91
36 I-187 0.58 13 I-191 1.1 11 I-196 1.4 6.8 I-197 6.7 38 I-198 7.2
33 I-199 4.8 31 I-202 6.7 67 I-204 1.0 6.3 I-205 2.9 17 I-206 5.9
54 I-207 4.6 23 I-210 1.1 13 I-212 0.67 7.5 I-213 0.44 4.0 Ia-1 4.8
31 Ia-3 9.2 150 Ia-4 1.4 15 Ia-5 1.6 43 Ia-6 2.4 23 Ia-8 2.9 34
Ia-9 0.94 11 Ia-10 0.47 2.7 Ia-11 0.64 7.2 Ia-12 0.94 5.5 Ia-13 1.5
3.3 Ia-14 4.8 28 Ia-16 0.1 -- Ia-17 0.1 1.9 Ia-20 4.9 100
[1194]
3 TABLE 3 Ia-21 3.4 35 Ia-22 3.1 38 Ia-24 5.2 74 Ia-25 1.1 18 Ia-26
1.9 27 Ia-28 5.2 130 Ia-29 1 7.3 Ia-30 2.6 25 Ia-31 3.8 11 Ia-32
0.52 6.7 Ia-33 1.8 64 Ia-35 1.8 -- Ia-36 1.6 86 Ia-37 0.73 3.8
Ia-38 1 2.2 Ia-39 1.5 3.5 Ia-40 2.2 9.3 Ia-41 2.5 9 Ia-42 3.6 20
Ia-44 4.8 27 Ia-45 4.8 42 Ia-46 0.87 8.3 Ia-47 0.82 3.8 Ia-48 1.2
6.1 Ia-49 2.6 83 Ia-50 1.7 24 Ia-51 1.3 3.4 Ia-52 1.9 22 Ia-53 0.22
8.1 Ia-54 0.44 9 Ia-55 1.1 27 Ia-56 2.3 96 Ia-57 0.93 31 Ia-58 2.5
110 Ia-59 0.71 16 Ia-60 0.95 10 Ia-61 0.68 19 Ia-62 1.1 29 Ia-63
3.9 370 Ia-64 7.1 96 Ia-65 1.1 11 Ia-66 0.59 3.2 Ia-67 6.3 75 Ia-68
9.5 180 Ia-69 2.7 33 Ia-70 1.5 31 Ia-71 1.3 12 Ia-76 2.2 -- Ia-78 2
150 Ia-79 0.82 -- Ia-80 0.44 3.0 Ia-81 2.7 4.5 Ia-83 1.2 53 Ia-84
0.25 13 Ia-85 0.22 14 Ia-86 0.73 11 Ia-87 0.49 61 Ia-88 0.62 48
Ia-91 4 150 Ia-106 1.9 24 Ia-107 0.14 1.3 Ia-109 0.6 3.9 Ia-110 0.3
1.1 Ia-111 5.1 28 Ia-124 1.1 22 Ia-125 4.1 46 Ia-126 2.3 58 Ia-127
6.1 160 Ia-129 1.3 26 Ia-130 0.21 3 Ia-131 1.3 17 Ia-132 2.8 76
Ia-133 1.7 8.8 Ia-135 8.2 49 Ia-136 1.6 13 Ia-138 2.2 28 Ia-139 1.9
25 Ia-140 1 24 Ia-141 1 5.7 Ia-142 0.67 5.5
[1195]
4 TABLE 4 Ia-143 7.8 39 Ia-144 6.1 57 Ia-145 7 86 Ia-146 9.9 79
Ia-158 0.71 1.7 Ia-160 0.76 140 Ia-161 1.9 18 Ia-163 7 400 Ia-164
0.38 4.7 Ia-168 0.95 13 Ia-169 1.9 88 Ia-173 6.9 140 Ia-174 0.35
5.4 Ia-175 0.49 9.2 Ia-176 0.63 5.1 Ia-177 0.49 7.5 Ia-178 4.6 16
Ia-179 0.89 19 Ia-180 1.9 11 Ia-181 7.7 25 Ia-182 0.24 2.1 Ia-183
1.9 7.8 Ia-184 0.38 -- Ia-185 0.94 4.4 Ia-186 0.93 12 Ia-187 1.9 60
Ia-188 0.75 28 Ia-189 3.5 95 Ia-190 0.34 1000 Ia-191 0.49 220
Ia-192 5.9 200 Ia-193 1.4 43 Ia-194 0.22 8.1 Ia-195 1.4 31 Ia-196
0.39 1.3 Ia-197 0.44 2.5 Ia-198 0.23 2.6 Ia-199 0.11 1.6 Ia-200 1.4
18 Ia-201 3.1 74 Ia-202 0.37 3.4 Ia-203 0.2 2.6 Ia-204 1 6.3 Ia-205
2.4 99 Ia-206 1.9 460 Ia-207 0.55 5.9 Ia-208 1.2 9.7 Ia-209 0.55 --
Ia-210 2.8 99 Ia-211 4.8 240 Ia-212 0.52 2.6 Ia-213 0.91 28 Ia-219
2.5 28 Ia-221 0.47 1.5 Ia-222 3.7 18 Ia-224 0.1 1.2 Ia-225 3.4 20
Ia-226 0.37 21 Ia-227 0.59 -- Ia-228 0.96 -- Ia-229 1.9 -- Ia-230
0.32 -- Ia-231 0.29 -- Ia-232 0.7 -- Ia-233 0.63 -- Ia-235 5.5 --
Ia-237 1.1 15 Ia-241 1.9 -- Ia-243 1.3 -- Ia-246 0.26 20 Ia-247
0.79 31 Ia-248 0.27 17 Ia-250 1.9 -- Ia-252 1.2 -- Ia-253 0.53 --
Ia-254 2.0 -- Ia-255 3.2 -- Ia-256 5.7 -- Ia-257 8.6 -- Ia-258 1.8
--
[1196] As shown in Tables 1 to 4, the compounds of the present
invention have an NPY Y5 receptor antagonistic activity.
[1197] Experiment 3
[1198] Using the membranes prepared from Y1-expression cells (human
neuroblastoma, SK-N-MC) and the membranes prepared from
Y2-expression cells (human neuroblastoma, SMS-KAN), the experiment
was carried out in a similar way as Experiment 1 to determine the
affinity for NPY Y1 receptor and NPY Y2 receptor.
[1199] Binding IC.sub.50 values for NPY Y1 and NPY Y2 receptors of
I-27, I-32, I-41, I-45, I-46, I-47, I-48, I-49, I-59, I-61, I-63,
I-64, I-66, I-69, I-72, I-152, I-154, I-204, I-205, I-212, Ia-3,
Ia-5, Ia-6, Ia-12, Ia-16, Ia-17, Ia-20, Ia-21, Ia-22, Ia-26, Ia-28,
Ia-29, Ia-30, Ia-31, Ia-32, Ia-33, Ia-37, Ia-39, Ia-40, Ia-50,
Ia-51, Ia-54, Ia-62, Ia-67, Ia-124, Ia-126, Ia-139, Ia-140, Ia-142,
Ia-178, Ia-199 and Ia-200 were 100,000 nM or higher and each
compound had a selectivity for NPY Y5 receptor.
[1200] Formulation Example 1 Tablets
5 Compound (I-1) 15 mg Starch 15 mg Lactose 15 mg Crystalline
cellulose 19 mg Polyvinyl alcohol 3 mg Distilled water 30 ml
Calcium stearate 3 mg
[1201] After all of the above ingredients except for calcium
stearate are uniformly mixed, the mixture is crushed and
granulated, and dried to obtain a suitable size of granules. After
calcium stearate is added to the granules, tablets are formed by
compression molding.
[1202] Formulation Example 2 Capsules
6 Compound (I-2) 10 mg Magnesium stearate 10 mg Lactose 80 mg
[1203] After the above ingredients are mixed to prepare powders or
granules the obtained are filled in capsules.
[1204] Formulation Example 3 Granules
7 Compound (I-3) 30 g Lactose 265 g Magnesium Stearate 5 g
[1205] After the above ingredients are mixed uniformly and formed
by compression molding, the obtained are crushed, granulated and
sieved to prepare suitable volume of granules.
[1206] Industrial Applicability
[1207] As shown in the above Experiments, the compounds of the
present invention have an NPY Y5 receptor antagonistic activity.
Therefore, the compounds of the present invention are useful as an
anti-obestic agent and anorectic agent.
* * * * *