U.S. patent application number 11/200480 was filed with the patent office on 2006-01-05 for inhibitors of hcv ns5b polymerase.
This patent application is currently assigned to Pharmacia & Upjohn Company, LLC. Invention is credited to Barry Craig Finzel, Hua Gao, Meredith L. Greene, Rebecca J. Gross, Richard Allen Nugent, Jeffrey A. Pfefferkorn.
Application Number | 20060004063 11/200480 |
Document ID | / |
Family ID | 30000931 |
Filed Date | 2006-01-05 |
United States Patent
Application |
20060004063 |
Kind Code |
A1 |
Finzel; Barry Craig ; et
al. |
January 5, 2006 |
Inhibitors of HCV NS5B polymerase
Abstract
The present invention provides compounds of Formula I,
compositions and methods that are useful for treating viral
infections and associated diseases, particularly HCV infections and
associated diseases. ##STR1##
Inventors: |
Finzel; Barry Craig;
(Kalamazoo, MI) ; Gao; Hua; (Salem, CT) ;
Greene; Meredith L.; (Kalamazoo, MI) ; Gross; Rebecca
J.; (Kalamazoo, MI) ; Nugent; Richard Allen;
(Ashland, MA) ; Pfefferkorn; Jeffrey A.; (Dexter,
MI) |
Correspondence
Address: |
AGOURON PHARMACEUTICALS, INC.
10777 SCIENCE CENTER DRIVE
SAN DIEGO
CA
92121
US
|
Assignee: |
Pharmacia & Upjohn Company,
LLC
|
Family ID: |
30000931 |
Appl. No.: |
11/200480 |
Filed: |
August 9, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10609959 |
Jun 30, 2003 |
|
|
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11200480 |
Aug 9, 2005 |
|
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60392759 |
Jul 1, 2002 |
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|
Current U.S.
Class: |
514/357 ;
514/408; 514/563; 546/335; 548/561; 562/450 |
Current CPC
Class: |
C07D 263/32 20130101;
A61P 43/00 20180101; C07D 285/06 20130101; A61P 31/12 20180101;
C07D 207/333 20130101; C07D 233/64 20130101; C07D 317/68 20130101;
C07D 409/04 20130101; C07D 333/60 20130101; A61P 31/14 20180101;
C07D 405/12 20130101; C07D 317/54 20130101; C07D 215/50 20130101;
C07D 413/12 20130101; C07D 277/56 20130101; C07D 307/54 20130101;
A61P 1/16 20180101; C07D 307/81 20130101; C07D 277/36 20130101;
C07D 333/40 20130101; C07D 409/12 20130101; C07D 307/64 20130101;
C07D 307/79 20130101 |
Class at
Publication: |
514/357 ;
514/408; 514/563; 548/561; 562/450; 546/335 |
International
Class: |
C07D 213/55 20060101
C07D213/55; A61K 31/195 20060101 A61K031/195; C07D 207/30 20060101
C07D207/30 |
Claims
1. A compound of formula 1: ##STR749## wherein: a) X represents a
covalent bond or is selected from the group NR2, S, O, C.dbd.O,
C(R2)(R'2), CF.sub.2, CCl.sub.2, CR2OR'2, CR2NR'2, SO, and
SO.sub.2; b) Y is selected from the group substituted or
unsubstituted alkyl, substituted or unsubstituted heteroalkyl,
substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl and substituted or unsubstituted heteroalkyl; c) Z is
selected from the group substituted or unsubstituted aryl and
substituted or unsubstituted heteroaryl; d) any two adjacent
substituents of Y or Z may be taken together to form a fused
carbocyclic or heterocyclic ring of 5 to 7 members; e) R1 is
selected from the group H, alkyl, hetero-C.sub.1-C.sub.8-alkyl,
halogen, CN, halo C.sub.1-C.sub.8-alkyl, aryl, heteroaryl,
cyclo-C.sub.1-C.sub.8-alkyl and ara-C.sub.1-C.sub.8-alkyl; f) R2 is
H, C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8 -alkenyl, hetero
C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 cycloalkyl, heterocyclo
C.sub.1-C.sub.8alkyl, aryl, ara C.sub.1C.sub.8 alkyl, heteroaryl or
heteroaralkyl; g) R3 is selected from the group H, OH, OR2,
N(R2)(R'2) and N(R2)-T-W where T represents a substituted or
unsubstituted alkyl or cycloalkyl group of 1-8 carbons; h) W is
selected from the group OH, N(R2)(R'2), CON(R2)(R'2), OCO
N(R2)(R'2), NCON(R2)(R'2) and CO.sub.2R2; i) A represents a
substituted or unsubstituted aromatic ring; j) the substituents X
and R1-double bond (R1C.dbd.) are connected to A in a 1,2 1,3 or
1,4 spatial relationship; and k) the substituents A and COR3 have
an E (trans) configuration with respect to the double bond to which
they are attached.
2. A compound of formula 1: ##STR750## a) wherein: X represents a
covalent bond or is selected from the group NR2, S, O, C.dbd.O,
C(R2)(R'2), CF.sub.2, CCl.sub.2, CR2OR'2, CR2NR'2, SO, and
SO.sub.2; b) Y is selected from the group substituted or
unsubstituted alkyl, substituted or unsubstituted heteroalkyl,
substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl and substituted or unsubstituted heteroalkyl; c) Z is
selected from the group substituted or unsubstituted aryl and
substituted or unsubstituted heteroaryl; d) any two adjacent
substituents of Y or Z may be taken together to form a fused
carbocyclic or heterocyclic ring of 5 to 7 members; e) R1 is
selected from the group H, alkyl, hetero-C.sub.1-C.sub.8-alkyl,
halogen, CN, halo C.sub.1-C.sub.8-alkyl, aryl, heteroaryl,
cyclo-C.sub.1-C.sub.8-alkyl and ara-C.sub.1-C.sub.8-alkyl; f) R2 is
H, C.sub.1-C.sub.8-alkyl, C.sub.1-C.sub.8 -alkenyl, hetero
C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 cycloalkyl, heterocyclo
C.sub.1-C.sub.8 alkyl, aryl, ara C.sub.1-C.sub.8 alkyl, heteroaryl
or heteroaralkyl; g) R3 is selected from the group H, OH, OR2,
N(R2)(R'2) and N(R2)-T-W where T represents a substituted or
unsubstituted alkyl or cycloalkyl group of 1-8 carbons; h) W is
selected from the group OH, N(R2)(R'2), CON(R2)(R'2), OCO
N(R2)(R'2), NCON(R2)(R'2) and CO.sub.2R2; i) A represents a
substituted or unsubstituted heteroaromatic ring of 5 or 6 members;
j) the substituents X and R1-double bond (R1C.dbd.) are connected
to A in a 1,2 1,3 or 1,4 spatial relationship; and k) the
substituents A and COR3 have an E (trans) configuration with
respect to the double bond to which they are attached.
Description
CROSS REFERENCE
[0001] This application is a continuation under 35 U.S.C. .sctn.
120 of U.S. patent application Ser. No. 10/609,959, filed Jun. 30,
2003, which claims priority to U.S. patent application Ser. No.
60/392,759, filed Jul. 1, 2002, all of which are herein
incorporated by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to compounds, process for
their synthesis, compositions and methods for the treatment and
prevention of hepatitis C virus (HCV) infection. In particular, the
present invention provides novel compounds, pharmaceutical
compositions containing such compounds and methods for using these
compounds in the treatment or prevention of HCV infection. The
present invention also provides processes and intermediates for the
synthesis of these compounds.
BACKGROUND OF THE INVENTION
[0003] Hepatitis C virus (HCV) is the major etiological agent of
post-transfusion and community-acquired non-A non-B hepatitis
worldwide. It is estimated that over 150 million people worldwide
are infected by the virus. A high percentage of carriers become
chronically infected and many progress to chronic liver disease,
so-called chronic hepatitis C. This group is in turn at high risk
for serious liver disease such as liver cirrhosis, hepatocellular
carcinoma and terminal liver disease leading to death.
[0004] The mechanism by which HCV establishes viral persistence and
causes a high rate of chronic liver disease has not been thoroughly
elucidated. It is not known how HCV interacts with and evades the
host immune system. In addition, the roles of cellular and humoral
immune responses in protection against HCV infection and disease
have yet to be established. Immunoglobulins have been reported for
prophylaxis of transfusion-associated viral hepatitis, however, the
Center for Disease Control does not presently recommend
immunoglobulins treatment for this purpose. The lack of an
effective protective immune response is hampering the development
of a vaccine or adequate post-exposure prophylaxis measures, so in
the near-term, hopes are firmly pinned on antiviral
interventions.
[0005] Various clinical studies have been conducted with the goal
of identifying pharmaceutical agents capable of effectively
treating HCV infection in patients afflicted with chronic hepatitis
C. These studies have involved the use of interferon-alpha, alone
and in combination with other antiviral agents. Such studies have
shown that a substantial number of the participants do not respond
to these therapies, and of those that do respond favorably, a large
proportion were found to relapse after termination of
treatment.
[0006] Until recently, interferon (IFN) was the only available
therapy of proven benefit approved in the clinic for patients with
chronic hepatitis C. However the sustained response rate is low,
and interferon treatment also induces severe side-effects (i.e.
retinopathy, thyroiditis, acute pancreatitis, depression) that
diminish the quality of life of treated patients. Recently,
interferon in combination with ribavirin has been approved for
patients non-responsive to IFN alone. However, the side effects
caused by IFN are not alleviated with this combination therapy.
[0007] Therefore, a need exists for the development of effective
antiviral agents for treatment of HCV infection that overcomes the
limitations of existing pharmaceutical therapies.
SUMMARY OF THE INVENTION
[0008] The present invention provides compounds, compositions and
methods that are useful for treating viral infections and
associated diseases, particularly HCV infections and associated
diseases. The compounds of the invention inhibit viral replication,
preferably HCV replication. The methods of the invention comprise
administering to an infected or susceptible host a therapeutically
or prophylactically effective amount of a compound as represented
by Formula 1, or a pharmaceutically acceptable salt or prodrug
thereof. ##STR2##
[0009] In Formula 1, X represents a covalent bond or is selected
from the group NR2, S, O, C.dbd.O, C(R2)(R'2), CF.sub.2, CCl.sub.2,
CR2OR'2, CR2NR'2, SO, and SO.sub.2; Y is selected from the group
substituted or unsubstituted alkyl, substituted or unsubstituted
heteroalkyl, substituted or unsubstituted aryl, and substituted or
unsubstituted heteroaryl; Z is selected from the group substituted
or unsubstituted aryl and substituted or unsubstituted
heteroaryl;
[0010] any two adjacent substituents of Y or Z may be taken
together to form a fused carbocyclic or heterocyclic ring of 5 to 7
members;
[0011] Y is selected from the group substituted or unsubstituted
alkyl, substituted or unsubstituted heteroalkyl, substituted or
unsubstituted aryl, and substituted or unsubstituted heteroaryl;
heteroaryl, cycloalkyl and aralkyl;
[0012] R2 is H, alkyl, alkenyl, heteroalkyl, cycloalkyl,
heterocycloalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl;
[0013] R3 is selected from the group H, OH, OR2, N(R2)(R'2) and
N(R2)-T-W where T represents a substituted or unsubstituted alkyl
or cycloalkyl group of 1-8 carbons; W is selected from the group
OH, N(R2)(R'2), CON(R2)(R'2), OCO N(R2)(R'2), NCON(R2)(R'2) and
CO.sub.2R2; A represents a substituted or unsubstituted aromatic or
heteroaromatic ring of 5 or 6 members;
[0014] the substituents X and R1C=are connected to A in a 1,2 1,3
or 1,4 spatial relationship; and
[0015] the substituents A and COR3 have an E (trans) configuration
with respect to the double bond to which they are attached.
DETAILED DESCRIPTION OF THE INVENTION
Abbreviations and Definitions
[0016] The abbreviations used herein are conventional, unless
otherwise defined.
[0017] The terms "treat", "treating" and "treatment" refer to a
method of alleviating or abrogating a disease and/or its attendant
symptoms.
[0018] The terms "prevent", "preventing" and "prevention" refer to
a method of "barring a subject from acquiring a disease. As used
herein, "prevent", "preventing" and "prevention" also include
reducing a subject's risk of acquiring a disease.
[0019] The term "therapeutically effective amount" refers to that
amount of the compound being administered sufficient to prevent
development of or alleviate to some extent one or more of the
symptoms of the disease being treated.
[0020] The term "viral infection" refers to the introduction of a
virus into cells or tissues, e.g., hepatitis C virus (HCV). In
general, the introduction of a virus is also associated with
replication. Viral infection may be determined by measuring virus
antibody titer in samples of a biological fluid, such as blood,
using, e.g., enzyme immunoassay. Other suitable diagnostic methods
include molecular based techniques, such as RT-PCR, direct hybrid
capture assay, nucleic acid sequence based amplification, and the
like. A virus may infect an organ, e.g., liver, and cause disease,
e.g., hepatitis, cirrhosis, chronic liver disease and
hepatocellular carcinoma.
[0021] "Flaviviridae virus", as used herein, refers to a virus of
the family Flaviviridae, which family includes the Flavivirus,
Pestivirus and Hepacivirus or hepatitis C-like virus genera.
Representative species of the genus Flavivirus include yellow fever
virus, tick-borne encephalitis virus, Rio Bravo virus, Japanese
encephalitis virus, Tyuleniy virus, Ntaya virus, Uganda S virus,
Dengue virus and Modoc virus. Representative species of the genus
Pestivirus include bovine diarrhea virus, border disease virus and
hog cholera virus. A representative species of the genus of
hepatitis C-like viruses is hepatitis C virus. Unassigned viruses
in the family Flaviviridae are included in the meaning of
Flaviviridae virus.
[0022] The term "modulate" refers to the ability of a compound to
increase or decrease the catalytic activity of a viral polymerase,
e.g. a viral RNA polymerase. A modulator preferably activates the
catalytic activity of a viral polymerase or more preferably
activates or inhibits the catalytic activity of a viral polymerase
depending on the concentration of the compound exposed to the viral
polymerase or most preferably inhibits the catalytic activity of a
viral polymerase.
[0023] The term "modify" refers to the act of altering, in whole or
in part, the structure of a molecule, e.g., a protein. Modification
may be covalent or noncovalent, and includes, but is not limited
to, aggregation, association, substitution, conjugation and/or
elimination of a chemical group. Modification may alter the
function or other properties (e.g., chemical, physical) of the
molecule.
[0024] The term "alkyl," by itself or as part of another
substituent, means, unless otherwise stated, a straight or branched
chain, or cyclic hydrocarbon radical, or combination thereof, which
may be fully saturated, mono- or polyunsaturated and can include
di- and multivalent radicals, having the number of carbon atoms
designated (i.e. C.sub.1-C.sub.8 means 1-8 eight carbons). Examples
of saturated hydrocarbon radicals include groups such as methyl,
ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl,
cyclohexyl, (cyclohexyl)ethyl, cyclopropylmethyl, homologs and
isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and
the like. An unsaturated alkyl group is one having one or more
double bonds or triple bonds. Examples of unsaturated alkyl groups
include vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl),
2,4-pentadienyl, 3 -(1,4-pentadienyl), ethynyl, I- and 3 -propynyl,
3 -butynyl, and the higher homologs and isomers. The term
"alkylene" by itself or as part of another substituent means a
divalent radical derived from an alkane, as exemplified by
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2--. A "lower alkyl" or "lower
alkylene" is a shorter chain alkyl or alkylene group, having eight
or fewer carbon atoms.
[0025] The terms "alkoxy", "alkylamino" and "alkylthio" refer to
those groups having an alkyl group attached to the remainder of the
molecule through an oxygen, nitrogen or sulfur atom, respectively.
Similarly, the term "dialkylamino" is used in a conventional sense
to refer to --NR'15R15'' wherein the R groups can be the same or
different alkyl groups.
[0026] The term "heteroalkyl," by itself or in combination with
another term, means, unless otherwise stated, a stable straight or
branched chain, or cyclic hydrocarbon radical, or combinations
thereof, fully saturated or containing from 1 to 3 degrees of
unsaturation, consisting of the stated number of carbon atoms and
from one to three heteroatoms selected from the group consisting of
O, N, and S, and wherein the nitrogen and sulfur atoms may
optionally be oxidized and the nitrogen heteroatom may optionally
be quaternized. The heteroatom(s) O, N and S may be placed at any
interior position of the heteroalkyl group. Examples include
--CH.sub.2--CH.sub.2--O--CH.sub.3,
--CH.sub.2--CH.sub.2--NH--CH.sub.3,
--CH.sub.2--CH.sub.2--N(CH.sub.3)--CH.sub.3,
--CH.sub.2--S--CH.sub.2--CH.sub.3,
--CH.sub.2--CH.sub.2--S(O)--CH.sub.3,
--CH.sub.2--CH.sub.2--S(O).sub.2--CH.sub.3,
--CH.dbd.CH--O--CH.sub.3, --Si(CH.sub.3).sub.3,
CH.sub.2--CH.dbd.N--OCH.sub.3, and
--CH.dbd.CH--N(CH.sub.3)--CH.sub.3. Up to two heteroatoms may be
consecutive, such as, for example, --CH.sub.2--NH--OCH.sub.3. Also
included in the term "heteroalkyl" are those radicals described in
more detail below as "heterocycloalkyl." The term "heteroalkylene"
by itself or as part of another substituent means a divalent
radical derived from heteroalkyl, as exemplified by
--CH.sub.2--CH.sub.2--S--CH.sub.2CH.sub.2-- and
--CH.sub.2--S--CH.sub.2CH.sub.2--NH--CH.sub.2--. For heteroalkylene
groups, heteroatoms can also occupy either or both of the chain
termini. Still further, for alkylene and heteroalkylene linking
groups, no orientation of the linking group is implied.
[0027] The terms "cycloalkyl" and "heterocycloalkyl", by themselves
or in combination with other terms, represent, unless otherwise
stated, cyclic versions of "alkyl" and "heteroalkyl", respectively.
Additionally, for heterocycloalkyl, a heteroatom can occupy the
position at which the heterocycle is attached to the remainder of
the molecule. Examples of cycloalkyl. include cyclopentyl,
cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the
like. Examples of heterocycloalkyl include 1-piperidinyl,
2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl,
tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl,
tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, and the
like.
[0028] The terms "halo" or "halogen," by themselves or as part of
another substituent, mean, unless otherwise stated, a fluorine,
chlorine, bromine, or iodine atom. Additionally, terms such as
"Fluoroalkyl," are meant to include monofluoroalkyl and
polyfluoroalkyl.
[0029] The term "aryl," employed alone or in combination with other
terms (e.g., aryloxy, arylthioxy, aralkyl) means, unless otherwise
stated, an aromatic substituent which can be a single ring or
multiple rings (up to three rings) which are fused together or
linked covalently. The term "heteroaryl" is meant to include those
aryl rings which contain from zero to four heteroatoms selected
from N, O, and S, wherein the nitrogen and sulfur atoms are
optionally oxidized, and the nitrogen atom(s) are optionally
quaternized. The "heteroaryl" groups can be attached to the
remainder of the molecule through a heteroatom. Non-limiting
examples of aryl and heteroaryl groups include phenyl, 1-naphthyl,
2-napthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,
3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl,
4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl,
4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl,
2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl,
4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl,
2-benzimidazolyl, 1-indolyl, 5-indolyl, 1-isoquinolyl,
5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and
6-quinolyl.
[0030] Substituents for each of the above noted aryl ring systems
are selected from the group of acceptable substituents described
below. The term "aralkyl" is meant to include those radicals in
which an aryl or heteroaryl group is attached to an alkyl group
(e.g., benzyl, phenethyl, pyridylmethyl and the like) or a
heteroalkyl group (e.g., phenoxymethyl, 2-pyridyloxymethyl,
3-(1-naphthyloxy)propyl, and the like).
[0031] Each of the above terms (e.g., "alkyl . . . heteroalkyl" and
"aryl") are meant to include both substituted and unsubstituted
forms of the indicated radical. Preferred substituents for each
type of radical are provided below.
[0032] Substituents for the alkyl and heteroalkyl radicals
(including those groups often referred to as alkylene, alkenyl,
heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl,
heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) can be a
variety of groups selected from: --OR', .dbd.O, .dbd.NR',
.dbd.N--OR', --NR'R''--SR', -halogen, --SiR'R''R, --OC(O)R',
--C(O)R', --CO.sub.2R', CONR'R'', --OC(O)NR'R''--NR'C(O)R',
--NR'--C(O)NR''R''', --NR'COOR'', --NH--C(NH.sub.2).dbd.NH,
--NR'C(NH.sub.2).dbd.N--H, --NH--C(NH.sub.2).dbd.NR', --S(O)R',
S(O).sub.2R', --S(O).sub.2NR'R'', --CN and --NO.sub.2 in a number
ranging from zero to (2N+1), where N is the total number of carbon
atoms in such radical. R', R'' and X'' each independently refer to
hydrogen, unsubstituted Cl-COalkyl and heteroalkyl, unsubstituted
aryl, aryl substituted with 1-3 halogens, unsubstituted alkyl,
alkoxy or thioalkoxy groups, or aryl-(C1 -C4)alkyl groups. When R'
and R'' are attached to the same nitrogen atom, they can be
combined with the nitrogen atom to form a 3-7 membered ring. For
example, --NR'R'' is meant to include 1-pyrrolidinyl and
4-morpholinyl. From the above discussion of substituents, one of
skill in the art will understand that the term "alkyl" is meant to
include groups such as haloalkyl (e.g., --CF.sub.3 and
--CH.sub.2CF.sub.3) and acyl (e.g., --C(O)CH.sub.3, --C(O)CF.sub.3,
--C(O)CH.sub.2OCH.sub.3, and the like).
[0033] Similarly, substituents for the aryl groups are varied and
are selected from: halogen, --OR, --OC(O)R, --NR'R'', --SR, --R',
--CN, --NO.sub.2, --CO.sub.2R', --CONR'R:', --C(O)R',
--OC(O)NR'R'', --NR''C(O)R', --NR''C(O).sub.2R',
--NR'--C(O)NR''R''', --NH--C(NH.sub.2).dbd.NH,
--NR'C(NH.sub.2).dbd.NH, --NH--C(NH.sub.2).dbd.NR', --S(O)R',
--S(O).sub.2R', --S(O).sub.2NR'R'', --N.sub.3, --CH(Ph).sub.2,
perfluoro(CI-C4)alkoxy, perfluoro(CI-C4)alkyl, in a number ranging
from zero to the total number of open valences on the aromatic ring
system; and where R', R'' and R''' are independently selected from
hydrogen, (C1-C8)alkyl and heteroalkyl, unsubstituted aryl,
(unsubstituted aryl)-(C1-C4)alkyl, and (unsubstituted
aryloxy-(C.sub.1-C.sub.4)alkyl.
[0034] Two of the substituents on adjacent atoms of the aryl ring
may optionally be replaced with a substituent of the formula
--S--C(O)--(CH.sub.2)q-R--, wherein S and R are independently
--NH--, --O--, --CH.sub.2-- or a single bond, and the subscript q
is an integer of from 0 to 2. Alternatively, two of the
substituents on adjacent atoms of the aryl ring may optionally be
replaced with a substituent of the formula -A-(CH.sub.2).sub.w-B--,
wherein A and B are independently --CH.sub.2--, --O--, --NH--,
--S--, --S(O)--, --S(O).sub.2--, --S(O).sub.2NR'-- or a single
bond, and w is an integer of from 1 to 3. One of the single bonds
of the new ring so formed may optionally be replaced with a double
bond. Alternatively, two of the substituents on adjacent atoms of
the aryl ring may optionally be replaced with a substituent of the
formula --(CH.sub.2).sub.w-G-(CH.sub.2).sub.w-- where w and w' are
independently integers of from 0 to 3, and G is --O--, --NR'--,
--S--, --S(O)--, --S(O).sub.2--, or --S(O).sub.2NR'--. The
substituent R' in --NR'-- and --S(O).sub.2NR'-- is selected from
hydrogen or unsubstituted (CI-C6)alkyl.
[0035] As used herein, the term "heteroatom" is meant to include
oxygen (O), nitrogen (N), ) and sulfur(S).
[0036] The term "pharmaceutically acceptable salts" is meant to
include salts of the active compounds which are prepared with
relatively nontoxic acids or bases, depending on the particular
substituents found on the compounds described herein. When
compounds of the present invention contain relatively acidic
functionalities, base addition salts can be obtained by contacting
the neutral form of such compounds with a sufficient amount of the
desired base, either neat or in a suitable inert solvent. Examples
of pharmaceutically acceptable base addition salts include sodium,
potassium, calcium, ammonium, organic amino, or magnesium salt, or
a similar salt. When compounds of the present invention contain
relatively basic functionalities, acid addition salts can be
obtained by contacting the neutral form of such compounds with a
sufficient amount of the desired acid, either neat or in a suitable
inert solvent. Examples of pharmaceutically acceptable acid
addition salts include those derived from inorganic acids like
hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic,
phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric,
monohydrogensulfuric, hydriodic, or phosphorous acids and the like,
as well as the salts derived from relatively nontoxic organic acids
like acetic, propionic, isobutyric, maleic, malonic, benzoic,
succinic, suberic, fumaric, mandelic, phthalic, benzenesulfonic,
p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like.
Also included are salts of amino acids such as arginate and the
like, and salts of organic acids like glucuronic or galactouronic
acids and the like (see, for example, Berge, S. M., et. al. (1977)
J. Pharm. Sci., 66:1-19). Certain specific compounds of the present
invention contain both basic and acidic functionalities that allow
the compounds to be converted into either base or acid addition
salts.
[0037] The neutral forms of the compounds may be regenerated by
contacting the salt with a base or acid and isolating the parent
compound in the conventional manner.
[0038] The parent form of the compound differs from the various
salt forms in certain physical properties, such as solubility in
polar solvents, but otherwise the salts are equivalent to the
parent form of the compound for the purposes of the present
invention.
[0039] In addition to salt forms, the present invention provides
compounds which are in a prodrug form. Prodrugs of the compounds
described herein are those compounds that readily undergo chemical
changes under physiological conditions to provide the compounds of
the present invention. Additionally, prodrugs can be converted to
the compounds of the present invention by chemical or biochemical
methods in an ex-vivo environment. For example, prodrugs can be
slowly converted to the compounds of the present invention when
placed in a transdermal patch reservoir with a suitable enzyme or
chemical reagent. Prodrugs are often useful because, in some
situations, they may be easier to administer than the parent drug.
They may, for instance, be bioavailable by oral administration
whereas the parent drug is not. The prodrug may also have improved
solubility in pharmacological compositions over the parent drug. A
wide variety of prodrug derivatives are known in the art, such as
those that rely on hydrolytic cleavage or oxidative activation of
the prodrug. An example, without limitation, of a prodrug would be
a compound of the present invention which is administered as an
ester (the "prodrug"), but then is metabolically hydrolyzed to the
carboxylic acid, the active entity. Additional examples include
peptidyl derivatives of a compound of the invention.
[0040] Certain compounds of the present invention can exist in
unsolvated forms as well as solvated forms, including hydrated
forms. In general, the solvated forms are equivalent to unsolvated
forms and are intended to be encompassed within the scope of the
present invention. Certain compounds of the present invention may
exist in multiple crystalline or amorphous forms. In general, all
physical forms are equivalent for the uses contemplated by the
present invention and are intended to be within the scope of the
present invention.
[0041] Certain compounds of the present invention possess
asymmetric carbon atoms (optical centers) or double bonds; the
racemates, diastereomers, geometric isomers and individual isomers
are all intended to be encompassed within the scope of the present
invention unless otherwise stated.
[0042] The compounds of the present invention may also contain
unnatural proportions of atomic isotopes at one or more of the
atoms that constitute such compounds. For example, the compounds
may be radiolabeled with radioactive isotopes, such as for example
tritium (.sup.3H), iodine-125 (.sup.125I) or carbon-14 (.sup.14C).
All isotopic variations of the compounds of the present invention,
whether radioactive or not, are intended to be encompassed within
the scope of the present invention.
Description of the Embodiments
[0043] General Viral polymerases are attractive targets for
antiviral drug development. For example, inhibitors of Viral RNA
polymerase activity have been described; see, for example, Jaen,
Juan, et. al., WO 0177091, Altamura et. al., WO 00/06529 and Bailey
et. al., WO 00/10573, which references are incorporated by
reference herein.
[0044] The HCV protein NS5B is an RNA dependent RNA polymerase,
see, e.g., Lohmann et al. (1997) J. Virol. 71:8416-8428, Behrens et
al. (1996) EMBO J 15:12-22 and Ishido et al. (1998) Biochem.
Biophys. Res. Comm. 244:35-40, which references are incorporated by
reference herein. The sequence of various genotypes of HCV NS5B are
known (Kato et al. (1990) Proc. Natl. Acad. Sci. USA. 87:9524-9528;
Webster, G., et al. (2000) Balliere's Clinical Gastroenterology 14,
229-240; van Doorn, L. J. (1994) J. of Medical Virology 43,
345-356; Houghton, M. (1996) Hepatitis C viruses Fields Virology:
Third Ed., edited by B. N. Fields, D. M. Knipe, P. M. Howley, et
al. Lippincoft-Raven Publishers, Philadelphia, pp. 1035-1058; Lau,
J. Y. et. al., J Infect Dis. 1995, 171(2), 281-9). However, NS5B
contains sequence motifs that are highly conserved among all the
RNA-dependent RNA polymerases characterized to date.
[0045] The present invention provides compounds having antiviral
activity. It is believed that the compounds of the invention will
block viral replication by specifically inhibiting the activity of
a viral polymerase. Viral RNA polymerase is required for the
transcription of genomic RNA, which process is required for
replication of the genome of an RNA virus. Therefore, inhibition of
viral RNA polymerase will inhibit viral replication.
[0046] Non-limiting examples of the embodiments are given in Table
1. TABLE-US-00001 TABLE 1 ##STR3## ##STR4## ##STR5## ##STR6##
##STR7## ##STR8## ##STR9## ##STR10## ##STR11## ##STR12## ##STR13##
##STR14## ##STR15## ##STR16## ##STR17## ##STR18## ##STR19##
##STR20## ##STR21## ##STR22##
Analysis of the Compounds
[0047] The subject compounds and compositions may be demonstrated
to have pharmacological activity, e.g, antiviral activity, in in
vitro and in vivo assays, as known in the art. See for example
Behrens, S. E., et. al EMBO J. 15:12-22; Lohmann, V., et. al.,
1997, J. Virol. 71:8416-8428; Ferrari, E., et al. 1999. J. Virol.
73:1649-1654; Bealieu, P. L. et. al., WO0204425 A2; Perni, R. B.
et. al., WO9833501; which references are incorporated by reference
herein.
[0048] The subject compounds and compositions are capable of
specifically inhibiting or suppressing a viral infection, e.g., an
HCV infection. An in vivo assessment of the antiviral activity of
the compounds of the invention may be made using an animal model of
viral infection, e.g., a primate model. Cell-based assays may be
performed using, e.g, a cell line directly infected with a virus.
Cell-based assays for activity against a specific viral component,
e.g., a polymerase, may also be performed. Additionally,
biochemical or mechanism-based assays, e.g., transcription assays
using a purified protein, Northern blot, RT-PCR, etc., may be
performed.
[0049] The above-described assays are exemplary and not intended to
limit the scope of the invention. The skilled practitioner can
appreciate that modifications can be made to conventional assays to
develop equivalent assays that obtain the same result.
[0050] High throughput assays for the presence, absence,
quantification, or other properties of particular compounds are
well known to those of skill in the art. Such assays may be adapted
to identify compounds capable of modifying a viral RNA dependent
RNA polymerase protein, e.g., NS5B using functional protein.
Preferred assays thus detect enhancement or inhibition of HCV
RNA-dependent RNA activity.
Compositions
[0051] In view of the antiviral activity associated with the
compounds described above, the present invention further provides
pharmaceutical compositions comprising one or more of the above
compounds in combination with a pharmaceutically acceptable
excipient.
[0052] In one embodiment, the invention provides the subject
compounds combined with a pharmaceutically acceptable excipient
such as sterile saline or other medium, water, gelatin, an oil,
etc. to form pharmaceutically acceptable compositions. The
compositions and/or compounds may be administered alone or in
combination with any convenient carrier, diluent, etc. and such
administration may be provided in single or multiple dosages.
Useful carriers include solid, semi-solid or liquid media including
water and non-toxic organic solvents.
[0053] In another embodiment, the invention provides the subject
compounds in the form of a prodrug, which can be metabolically or
chemically converted to the subject compound by the recipient host.
A wide variety of prodrug derivatives are known in the art such as
those that rely on hydrolytic cleavage or oxidative activation of
the prodrug.
[0054] The compositions may be provided in any convenient form,
including tablets, capsules, lozenges, troches, hard candies,
powders, sprays, creams, suppositories, etc. As such, the
compositions, in pharmaceutically acceptable dosage units or in
bulk, may be incorporated into a wide variety of containers. For
example, dosage units may be included in a variety of containers
including capsules, pills, etc.
Methods of Use
[0055] In yet another aspect, the present invention provides novel
methods for the use of the foregoing compounds and compositions. In
particular, the invention provides novel methods for treating or
preventing viral infections, e.g., HCV infection. The invention
also provides novel methods for treating or preventing diseases
resulting from, in whole or in part, viral infections, preferably
diseases resulting from, in whole or in part, infection, such as
hepatitis C, cirrhosis, chronic liver disease and hepatocellular
carcinoma. The methods typically involve administering to a patient
an effective amount of one or more of the subject compounds or
compositions.
[0056] The compositions may be advantageously combined and/or used
in combination with other antiviral agents which are either
therapeutic or prophylactic agents, and different from the subject
compounds. The compositions may also be advantageously combined
and/or used in combination with agents that treat conditions often
associated with the viral infections that are sensitive to the
present compounds, such as anti-HIV agents or immunosuppressive
agents. In many instances, administration in conjunction with the
subject compositions enhances the efficacy of such agents.
Accordingly, the present compounds, when combined or administered
in combination with other antiviral agents, can be used in dosages
which are less than the expected amounts when used alone, or less
than the calculated amounts for combination therapy.
[0057] Exemplary treatment options for hepatitis C (HCV) include
interferons, e.g., interferon alfa-2b, interferon alfa-2a, and
interferon alfacon-1. Less frequent interferon dosing can be
achieved using pegylated interferon (interferon attached to a
polyethylene glycol moiety which significantly improves its
pharmacokinetic profile). Combination therapy with interferon
alfa-2b (pegylated and unpegylated) and ribavarin has also been
shown to be efficacious for some patient populations. Other agents
currently being developed include RNA replication inhibitors,
antisense agents, therapeutic vaccines, protease inhibitors,
helicase inhibitors and antibody therapy (monoclonal and
polyclonal).
[0058] The compounds and compositions of the present invention may
also be used with agents that enhance the bodys immune system,
including low-dose cyclophosphamide, thymostimulin, vitamins and
nutritional supplements (e.g., antioxidants, including vitamins A,
C, E, beta-carotene, zinc, selenium, glutathione, coenzyme Q-10 and
echinacea), and vaccines, e.g., the immunostimulating complex
(ISCOM), which comprises a vaccine formulation that combines a
multimeric 5 presentation of antigen and an adjuvant.
[0059] The compositions and compounds of the invention and the
pharmaceutically acceptable salts thereof can be administered in
any effective way such as via oral, parenteral or topical routes.
Generally, the compounds are administered in dosages ranging from
about 2 mg up to about 2,000 mg per day, although variations will
necessarily occur depending on the disease target, the patient, and
the route of administration. Preferred dosages are administered
orally in the range of about 0.05 mg/kg to about 20 mg/kg, more
preferably in the range of about 0.05 mg/kg to about 2 mg/kg, most
preferably in the range of about 0.05 mg/kg to about 0.2 mg per kg
of body weight per day.
Preparation of the Compounds
[0060] The compounds of this invention can be prepared by one or
more of the following schemes. ##STR23## ##STR24##
[0061] In Scheme 1, R1-3, A, X and Z are as defined above. The
reaction of I with II to give III, can be accomplished using
palladium catalyzed coupling chemistry well described in the art
(Bussalari, J. C., et. al., Org. Lett., 1999, 1, 965; Yeager, G.
W., et. al., Synthesis, 1991, 61; Hartwig, J. F., et. al., J. Org.
Chem., 1999, 64, 5575; Alonso, D. A., et. al., Org. Lett., 2000, 2,
1823; Huff, B. E., et. al. Org. Synth., 1997, 75, 53).
[0062] Thus, M1 is selected from the group F, Cl, Br, and I;
[0063] M2 is selected from the group B(OH).sub.2, Sn(R'2).sub.3,
NHR2 and OSO.sub.2CF.sub.3;
[0064] alternatively, when M2 is selected from the group F, Cl, Br,
and I;
[0065] M1 is selected from the group B(OH).sub.2, Sn(R'2).sub.3,
NHR2 and OSO.sub.2CF.sub.3.
[0066] The reaction of I with II may also be accomplished using
standard methodology when The reaction of I with II may also be
accomplished using standard methodology when M1 is an acid halide,
aryl halide, alkyl halide and the like and M2 is OH, SH, or NHR2,
or, as appropriate, when M2 is an acid halide aryl halide, alkyl
halide and the like and M1 is OH, SH, or NHR2.
[0067] In the reaction of III with IV to give the title compounds,
P represents a substituted phosphorous as found in Wittig,
Wittig-Horner, and the like, reagents. Examples of P include
dialkoxy phosphonate, dialkyl phosphinate and the like.
[0068] Conditions for the reaction of III with IV to give the
compounds of Formula 1 are also well known in the art. See for
example Moody, C. J., et. al., Chem. Commun. 1997, 2391; Beecher,
J. E., et. al., Tetrahedron Lett., (1998), 39, 3927; Dumas, M. et.
al., Tetrahedron Lett., (1989), 30, 5121; Schiavi, B. M., et. al.,
J. Org. Chem. (2002), 67, 620.
[0069] Scheme 2 represents the well-known azlactone synthesis. See
for example Herbst, R. M. et. al. in Organic Synthesis, Vol. 2,
p.1.
[0070] It is obvious to one of ordinary skill in the art that
further transformations of the products and intermediates of
Schemes 1 and 2 are readily achieved using methods common in the
art. These transformations include for example, ester, nitrile and
amide hydrolysis; ester, amide and nitrile reduction; primary and
secondary amine alkylation, acylation, aroylation; alcohol
acylation, aroylation and alkylation; and the like.
EXAMPLES
[0071] The following examples further illustrate the preparation
and analysis of compounds of the invention. The examples are
illustrative only and not intended to limit the scope of the
invention in any way. Reagents and solvents can be obtained from
commercial sources such as Aldrich Chemical Co. (Milwaukee, Wis.,
USA). All commercially obtained reagents are used as received
without further purification. Solvents are used as received or
dried over appropriate drying agents and distilled. Proton NMR
experiments are carried out on a Bruker 400 MHz spectrometer, and
chemical shifts are reported in ppm downfield from internal TMS.
Carbon NMR experiments are carried out on a Bruker 500 MHz
spectrometer, and chemical shifts are reported in ppm relative to
the central line of deuteriochloroform at 77.0 ppm. Low resolution
mass spectra (ESI) are obtained on a Micromass Platform C
spectrograph. Low resolution mass spectra (El) and high resolution
mass spectra (FAB), as well as IR spectra and elemental analyses
are conducted by the Pharmacia analytical laboratory. Flash column
chromatography is carried out on Biotage 40 prepacked columns,
while preparative TLC is carried out on Merck silica gel
F.sub.254-coated plates with 0.25 mm or 0.5 mm silica layers.
Unless otherwise noted, reactions are carried out in dry glassware
under a nitrogen atmosphere.
Example 1
(2Z)-2-(benzoylamino)-3-[5-(2-methylphenyl)-2-furyl]prop-2-enoic
acid
[0072] ##STR25##
[0073] a) As illustrated in Scheme 1, to a mixture of
5-bromo-2-furaldehyde (2.0 g, 11.4 mmol), tetrabutylammonium
bromide (3.7 g, 11.4 mmol), potassium carbonate (3.93 g, 28.5
mmol), 2-methylphenyl boronic acid (1.7 g, 12.5 mmol) and palladium
(II) acetate (55.2 mg, 0.23 mmol) is added water (20 mL). The
reaction mixture is then stirred vigorously for 16 hour at
25.degree. C. Once complete, the reaction mixture is poured into a
separatory funnel and diluted with water (50 mL) and ethyl acetate
(150 mL). The organic layer is separated and treated with 5.0 g of
activated charcoal for 30 min after which time the suspension is
filtered through a pad of celite and the filtrate concentrated to
afford the crude coupling product as a yellow oil. The crude
product is purified by column chromatography (5.fwdarw.10% ethyl
acetate in hexanes) to afford 1.8 g of
5-(2'-methylphenyl)-2-furaldehyde.
[0074] b) To a solution of
V-(benzyloxycarbonyl)-.alpha.-phosphonoglycine trimethyl ester
(20.0 g, 60.4 mmol) in methanol (300 mL) is added 10% Pd/C (200
mg). The flask is subsequently evacuated and treated with hydrogen
gas (3 atm) for 8 hours after which time the flask is evacuated and
filled with nitrogen. The reaction mixture is filtered through a
pad of celite and concentrated under reduced pressure to afford
11.3 g of .alpha.-phosphonoglycine trimethyl ester which is used
without further purification.
[0075] c) To a solution of .alpha.-phosphonoglycine trimethyl ester
(11.3 g, 57.4 mmol), prepared as described above, in
CH.sub.2Cl.sub.2 (200 mL) at 0.degree. C. is added triethylamine
(16.1 mL, 86.1 mmol) followed by benzoyl chloride (7.3 mL, 63.1
mmol). The reaction is stirred at 0.degree. C. for 1 hour and then
at 25.degree. C. for 12 hours. The reaction mixture is then poured
into a separatory funnel and washed saturated sodium bicarbonate
solution. The organic layer is dried over sodium sulfate before
being concentrated under reduced pressure. The crude product is
purified by column chromatography (50.fwdarw.100% ethyl acetate in
hexanes) to afford 13.9 g of N-benzoyl-.alpha.-phosphonoglycine
trimethyl ester.
[0076] d) To a solution of N-benzoyl-.alpha.-phosphonoglycine
trimethyl ester (200 mg, 0.66 mmol), prepared as described above,
in CH.sub.2Cl.sub.2 (5 mL) at 25.degree. C. is added
1,8-diazabicyclo[5.4.0]undec-7-ene (108 pi, 0.726 mmol) and the
reaction stirred for 10 minutes. A second solution of
5-(2'-methylphenyl)-2-furaldehyde (124 mg, 0.66 mmol), prepared as
described above, in CH.sub.2Cl.sub.2 (5 mL) is added and the
combined reaction mixture is stirred at 25.degree. C. for 2 hours.
Once complete, the reaction mixture is washed with 10% HCl and the
organic layer is dried over sodium sulfate and concentrated to
provide the crude product as an oil. This crude product is purified
by column chromatography (30% ethyl acetate in hexanes) to afford
104 mg of 1-methyl
(Z)-2-(benzoylamino)-3-[4-(2-methylphenoxy)phenyl]prop-2-enoate.
[0077] e) To a solution of 1-methyl
(Z)-2-(benzoylamino)-3-[4-(2-methylphenoxy)phenyl]prop-2-enoate
(104 mg, 0.29 mmol), prepared as described above, in dioxane (5 mL)
is added 1 N LiOH (5 mL). The reaction mixture is stirred at
25.degree. C. for 3 hours. The dioxane is then removed under
reduced pressure and the remaining reaction mixture poured into a
separatory funnel. The aqueous layer is washed with diethyl ether
and then acidified (pH=4) by treatment with 10% HCl causing a white
precipitate to develop. A portion of ethyl acetate (50 mL) is added
and the organic layer is separated, dried over sodium sulfate and
concentrated to afford 75 mg of
(Z)-2-(benzoylamino)-3-[5-(2-methylphenyl)-2-furyl]prop-2-enoic
acid which does not require a further purification.
Example 2
(2Z)-2-(benzoylamino)-3-(2'-chloro-fluoro-1,1'-biphenyl-3-yl)prop-2-enoic
acid
[0078] ##STR26##
[0079] a) To a solution of 2-bromo-4-fluorobenzaldehyde (2.0 g,
9.85 mmol) and 2-chlorophenylboronic acid (2.0 g, 12.1 mmol) in
ethylene glycol dimethyl ether (20 mL) is added 2N sodium carbonate
(19.7 mL) followed by tetrakis(triphenylphosphine) palladium (0)
(573 mg, 0.50 mmol). The reaction is subsequently stirred at
80.degree. C. for 4 hours under an argon atmosphere. Once complete,
the reaction mixture is poured into CH.sub.2Cl.sub.2 and water is
added. The organic layer is separated, dried over sodium sulfate
and concentrated to provide a crude oil. The crude product is
purified by column chromatography (10% ethyl acetate in hexanes) to
afford 1.25 g of 3-(2-chlorophenyl)-4-fluorobenzaldehyde.
[0080] b) A portion of 3-(2-chlorophenyl)-4-fluorobenzaldehyde,
prepared as described above, is subsequently converted to
Z-2-(benzoylamino)-3-(2'-chloro-6-fluoro-1,1'-biphenyl-3-yl)prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 3
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1,3-thiazol4-yl]prop-2-enoic
acid
[0081] ##STR27##
[0082] a) According to literature reference (Kelly, T. R.; Lang,
F., J. Org. Chem. 1996, 61, 4623-4633), ethyl bromopyruvate (10.0
mL, 79.7 mmol) and thiourea (5.5 g, 72.3 mmol) are combined neat in
a 100 mL flask and slowly heated to 100.degree. C. over a 1 hour
period. At approximately 70.degree. C. a vigorous reaction occurs
and the mixture becomes homogeneous. After reaching 100.degree. C.
the reaction is heated for an additional 20 minutes and then cooled
to room temperature. Upon cooling the reaction product solidifies
affording 19.0 grams of a crude ethyl 2-amino-4-thiazolecarboxylate
which is used without further purification.
[0083] b) Acording to literature reference (Kelly, T. R.; Lang, F.,
J. Org. Chem. 1996, 61, 4623-4633), crude ethyl
2-amino-4-thiazolecarboxylate (19.0 g, 111 mmol) is combined with
sodium bromide (46.7 g, 444 mmol) and copper (II) sulfate (52.4 g,
333 mmol). A portion of 9N sulfuric acid (225 mL) is then added and
the reaction mixture is cooled in an ice/salt bath. A solution of
sodium nitrate (8.35 g, 122 mmol) in water (100 mL) is added drop
wise to this reaction mixture over 30 minutes while maintaining the
reaction temperature at 0.degree. C. Once the addition is complete,
the reaction mixture is stirred at 0.degree. C. for 30 minutes and
at 25.degree. C. for an additional 1.5 hours. A portion of water
(300 mL) is then added and the reaction mixture extracted with
diethyl ether. Subsequently, the aqueous layer is made basic (pH 9)
by addition of 20% sodium hydroxide and then extracted a second
time with diethyl ether. The combined organic extracts are dried
over sodium sulfate and concentrated. The crude product is purified
by column chromatography (20% ethyl acetate in hexanes) to afford
5.06 g of ethyl 2-bromo-4-thiazolecarboxylate.
[0084] c) To a solution of ethyl 2-bromo-4-thiazolecarboxylate (2.0
g, 8.5 mmol), prepared as described above, in ethylene glycol
diethyl ether (15 mL) is added 2-chlorophenylboronic acid (1.73 9,
11.1 mmol), 2N sodium carbonate (17 mL) and
tetrakis(triphenylphosphine) palladium (0) (492 mg, 0.43 mmol). The
reaction is subsequently sealed and heated to 80.degree. C. for 3
hours under an argon atmosphere. Once complete, the reaction
mixture is poured into CH.sub.2Cl.sub.2 and of water is added. The
organic layer is separated, dried over sodium sulfate and
concentrated to provide a yellow oil. The crude product is purified
by column chromatography (10% ethyl acetate in hexanes) to afford
1.44 g of ethyl 2-(2-chlorophenyl)-4-thiazolecarboxylate.
[0085] d) To a solution of ethyl
2-(2-chlorophenyl)-4-thiazolecarboxylate (1.34 g, 5.0 mmol),
prepared as described above, in CH.sub.2Cl.sub.2 (20 mL) at
-78.degree. C. is added diisobutylaluminum hydride (10.5 mL of 1.0
M solution in toluene, 10.5 mmol) and the resulting reaction
mixture is stirred at -78.degree. C. for 1 hour after which time
sodium fluoride (1.5 g) and water (0.5 mL) are added and the
reaction mixture is allowed to warm to room temperature and
filtered. The filtrate is concentrated to provide the crude
reduction product which is purified by column chromatography (10%
ethyl acetate in hexanes) to afford 138 mg of
[2-(2-chlorophenyl)-1,3-thiazol-4-yl]carboxyaldehyde and 605 mg of
[2-(2-chlorophenyl)-1,3-thiazol-4-yl]methanol. The of
[2-(2-chlorophenyl)-1,3-thiazol-4-yl]carboxyaldehyde portion is
then used for subsequent steps while the
[2-(2-chlorophenyl)-1,3-thiazol-4-yl]methanol portion is converted
to [2-(2-chlorophenyl)-1,3-thiazol-4-yl]carboxyaldehyde via
standard oxidation conditions.
[0086] e) A portion of
[2-(2-chlorophenyl)-1,3-thiazol-4-yl]carboxyaldehyde, prepared as
described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 4
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1H-imidazol-5-yl]prop-2-enoic
acid
[0087] ##STR28##
[0088] a) According to literature reference (Huang, Y.; Luedtke, R.
R.; Freeman, R. A.; Wu, L.; Mach, R. H., Bioorg. Med. Chem. 2001,
9, 3113-3122), to a solution of hexamethyldisilazane (36.7 mL, 175
mmol) in of diethyl ether (300 mL) at 0.degree. C. is added n-butyl
lithium (114 mL of 1.6 M solution in hexanes, 182 mmol) and the
reaction mixture is stirred at 0.degree. C. for 30 minutes after
which time 2-chlorobenzonitrile (10.0 grams, 72.7 mmol) is added
and the reaction mixture is warmed to 25.degree. C. and stirred for
5 hours. Once complete, the reaction is poured into 2 N HCl and the
aqueous phase was washed twice with diethyl ether. This aqueous
phase is then made basic (pH =12) by addition of 6N sodium
hydroxide. Subsequently, the aqueous phase is extracted with
CH.sub.2Cl.sub.2 and the combined organic extracts are dried over
sodium sulfate and concentrated to provide a crude solid. The crude
product is then recrystallized from ethyl acetate to afford 5.4 g
of 2-chlorobenzenecarboximidamide. b) According to literature
reference (Huang, Y.; Luedtke, R. R.; Freeman, R. A.; Wu, L.; Mach,
R. H., Bioorg. Med. Chem. 2001, 9, 3113-3122), to a mixture of
2-chlorobenzenecarboximidamide (5.4 g, 34.8 mmol),
1,3-dihydroxyacetone dimmer (6.2 g, 34.8 mmol) and ammonium
chloride (7.5 g, 139 mmol) is added concentrated ammonium hydroxide
(40 mL). The reaction mixture is then heated to reflux for 30
minutes after which time it is cooled to room temperature and
poured into a ice/water mixture. This aqueous suspension is
extracted with CH.sub.2Cl.sub.2 and the combined organic extracts
are dried over sodium sulfate and concentrated to provide a crude
solid. The crude product is recrystallized from ethyl acetate to
afford 3.9 g of [2-(2-chlorophenyl)-1 H-imidazol-4-yl]methanol.
[0089] c) To a solution of
[2-(2-chlorophenyl)-1H-imidazol-4-yl]methanol (1.0 g, 4.81 mmol) in
CH.sub.2Cl.sub.2 (50 mL) at to 25.degree. C. is added sodium
bicarbonate (1.21 g, 14.4 mmol) followed by Dess-Martin periodinane
(2.29 g, 5.29 mmol). The reaction mixture is then stirred at to
25.degree. C. for 1 hour. Subsequently, the reaction mixture is
poured into a separatory funnel, diluted with CH.sub.2Cl.sub.2 and
washed with a saturated sodium sulfite solution. The organic layer
is dried over sodium sulfate and concentrated. The crude product is
purified by column chromatography (50% ethyl acetate in hexanes) to
afford 182 mg of
2-(2-chlorophenyl)-1H-imidazole-4-carbaldehyde.
[0090] d) A portion of
2-(2-chlorophenyl)-1H-imidazole-4-carbaldehyde, prepared as
described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1H-imidazol-5-yl]prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 5
(2Z)-2-(benzoylamino)-3-(5-phenyl-1,3-oxazol-2-yl)prop-2-enoic
acid
[0091] ##STR29##
[0092] a) According to reference (Synthesis 1984, 1048-1050), to a
solution of 5-phenyloxazole (1.5 g, 10.3 mmol) in THF:diethyl ether
(2:1, 50 mL) at -78.degree. C. is added n-butyl lithium (7.1 mL of
1.6 M solution in hexanes, 11.4 mmol). The reaction is stirred at
-78.degree. C. for 30 minutes after which time a solution of
N-methyl-2-pyridyl formamide (1.85 mL, 15.5 mmol) in THF (20 mL) is
added. The reaction mixture is stirred at -78.degree. C. for 30 min
and then at 25.degree. C. for 14 hours. It is quenched by addition
of water and extracted with ethyl acetate. The combined organic
layers are washed with 10% HCl, saturated sodium bicarbonate and
brine before being dried over sodium sulfate and concentrated. The
resulting oil is purified by column chromatography (5% ethyl
acetate in hexanes) to afford 246 mg of
5-phenyl-1,3-oxazole-2-carbaldehyde.
[0093] b) A portion of 5-phenyl-1,3-oxazole-2-carbaldehyde,
prepared as described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-(5-phenyl-1,3-oxazol-2-yl)prop-2-enoic acid
using steps (d) and (e) previously described for Example 1.
Example 6
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]prop-2-enoic
acid
[0094] ##STR30##
[0095] a) To a mixture of 4-fluorobenzaldehyde (2.5 g, 20.2 mmol),
2-bromophenol (3.5 g, 20.2 mmol) and potassium carbonate (3.35 g,
24.3 mmol) is added N,N-dimethylacetamide (20 mL) and the resulting
reaction mixture is heated to 150.degree. C. for 12 hours. Once
complete, the reaction is cooled to room temperature and diluted
with water prior to being extracted with ethyl acetate. The
combined extracts are washed with brine and dried over sodium
sulfate and concentrated. The resulting yellow oil is purified by
column chromatography (5% ethyl acetate in hexanes) to afford 2.1 g
of 4-(2-bromophenoxy)benzaldehyde.
[0096] b) A portion of 4-(2-bromophenoxy)benzaldehyde, prepared as
described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]prop-2-enoic acid
using steps (d) and (e) previously described for Example 1.
Example 7
(2Z)-2-(benzoylamino)-3-[3-(2-chlorophenoxy)phenyl]prop-2-enoic
acid
[0097] ##STR31##
[0098] a) To a mixture of 3-cyanophenyl boronic acid (2.84 g, 19.3
mmol), 2-chlorophenol (1.24 g, 9.64 mmol), copper (II) acetate
(1.75 g, 9.64 mmol) and 4 .ANG. molecular sieves is added
CH.sub.2Cl.sub.2 (30 mL). While stirring at 25.degree. C., pyridine
(3.89 mL, 48.2 mmol) of is added and the reaction mixture stirred
at 25.degree. C. for 48 hours. Once complete, the reaction is
filtered, and the resulting filtrate is concentrated to afford a
crude oil which is purified by column chromatography (5% ethyl
acetate in hexanes) to provide 1.92 g of
3-(2-chlorophenoxy)benzonitrile.
[0099] b) To a solution of 4-(2-chlorophenoxy)benzonitrile (1.92 g,
8.34 mmol) in toluene:CH.sub.2Cl.sub.2 (5:1, 100 mL) at -78.degree.
C. is added diisobutylaluminum hydride (13.4 mL of 1.0M solution in
toluene, 13.4 mmol). Once addition is complete, the reaction is
stirred at -78.degree. C. for 30 minutes and then at 25.degree. C.
for 2 hours. The reaction mixture is quenched by drop wise addition
of methanol (2 mL) followed by the addition of 10% HCl (10 mL).
After stirring at 25.degree. C. for 15 minutes, quenched reaction
mixture is extracted with chloroform and the combined organic
layers are dried over sodium sulfate and concentrated. The crude
product is purified by column chromatography (10% ethyl acetate in
hexanes) to afford 593 mg of 3-(2-chlorophenoxy)benzaldehyde.
[0100] c) A portion of 3-(2-chlorophenoxy)benzaldehyde, prepared as
described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-[3-(2-chlorophenoxy)phenyl]prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 8
(2Z)-2-(benzoylamino)-3-{4-[(4-methylbenzyl)oxy]phenyl)prop-2-enoic
acid
[0101] ##STR32##
[0102] a) To a solution of 4-hydroxybenzaldehyde (2.0 g, 13.9 mmol)
in acetone (80 mL) is added potassium carbonate (2.3 g, 16.7 mmol)
and 4-methyl benzyl bromide (2.57 g, 13.9 mmol). The reaction
mixture is stirred at 25.degree. C. for 12 hours after which time
the reaction solvent is removed by evaporation. The residue is
taken up in diethyl ether and transferred to a separatory funnel
wherein the organic layer is washed with water, 1 N sodium
hydroxide and brine before being dried over sodium sulfate and
concentrated. The resulting crude oil is purified by column
chromatography (5% ethyl acetate in hexanes) to 1.4 g of
4-[(4-methylbenzyl)oxy]benzaldehyde.
[0103] b) A portion of 4-[(4-methylbenzyl)oxy]benzaldehyde,
prepared as described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-{4-[(4-methylbenzyl)oxy]phenyl}prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 9
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorophenyl)amino]phenyl}prop-2-enoic
acid
[0104] ##STR33##
[0105] a) To a solution of 4-bromobenzonitrile (3.0 g, 16.4 mmol)
in toluene (40 mL) is added 2-chloroaniline (2.09 mL, 19.7 mmol),
cesium carbonate (7.5 9, 23.0 mmol), palladium (II) acetate (110
mg, 0.50 mmol) and S-BINAP (460 mg, 0.74 mmol). The reaction
mixture is then heated to 100.degree. C. for 12 hours under an
argon atmosphere. Once complete, the reaction is cooled to room
temperature, diluted with diethyl ether and filtered. The filtrate
is then concentrated and purified by column chromatography (6%
ethyl acetate in hexanes) to afford 1.35 g of
4-[(2-chlorophenyl)amino]benzonitrile.
[0106] b) To a solution of 4-[(2-chlorophenyl)amino]benzonitrile
(1.2 9, 5.24 mmol) in toluene:CH.sub.2Cl.sub.2 (5:1, 50 mL) at
-78.degree. C. is added diisobutylaluminum hydride (7.9 mL of 1.0 M
solution in toluene, 7.9 mmol). Once addition was complete, the
reaction is stirred at -78.degree. C. for 30 minutes and then at
25.degree. C. for 2 hours. The reaction mixture is quenched by drop
wise addition of methanol (2 mL) followed by the addition of 10%
HCl (10 mL). After stirring at 25.degree. C. for 15 minutes, the
quenched reaction mixture is extracted with chloroform and the
combined organic layers are dried over sodium sulfate and
concentrated. The crude product is purified by column
chromatography (15% ethyl acetate in hexanes) to afford 854 mg of
4-[(2-chlorophenyl)amino]benzaldehyde.
[0107] c) A portion of 4-[(2-chlorophenyl)amino]benzaldehyde,
prepared as described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorophenyl)amino]phenyl}prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 10
(2Z)-2-(benzoylamino)-3-(5-[(2-chlorophenyl)thio]-2-furyl}prop-2-enoic
acid
[0108] ##STR34##
[0109] a) To a solution of 2-chlorothiophenol (1.96 g, 13.6 mmol)
in THF (20 mL) at 0.degree. C. is slowly added sodium hydride (550
mg of 60% suspension in mineral oil, 13.7 mmol). After gas
evolution ceased, 5-bromo-2-furaldehyde (2.0 g, 11.4 mmol) is added
and the reaction mixture stirred at 0.degree. C. for 30 minutes and
then at 25.degree. C. for 1 hour. Once complete, the reaction is
quenched by addition of saturated ammonium chloride and extracted
with ethyl acetate. The combined organic extracts are dried over
sodium sulfate and concentrated. The resulting yellow oil is
purified by column chromatography (3% diethyl ether in hexanes) to
afford 1.3 g of 5-[(2-chlorophenyl)thio]-2-furylaldehyde.
[0110] b) A portion of 5-[(2-chlorophenyl)thio]-2-furylaldehyde,
prepared as described above, is subsequently converted to
(2Z)-2-(benzoylamino)-3-{5-[(2-chlorophenyl)thio]-2-furyl}prop-2-enoic
acid using steps (d) and (e) previously described for Example
1.
Example 11
(2Z)-2-(2-furoylamino)-3-(5-phenyl-2-furyl)prop-2-enoic acid
[0111] ##STR35##
[0112] a) As illustrated in Scheme 2, N-2-furoylglycine (131 mg,
0.776 mmol) is suspended in acetic anhydride (1 mL) and sodium
acetate (76 mg, 0.931 mmol) and 5-phenylfuraldehyde (170 mg, 1
mmol) are added. The reaction mixture is shaken at 60.degree. C.
for one hour, and cooled to 0.degree. C.. The resulting orange
solid is filtered and washed with ice water (75 mL) and heptane (50
mL). The solid is then dried under vacuum at 40.degree. C. to
afford 79 mg of
(4Z)-2-(2-furyl)-4-[(5-phenyl-2-furyl)methylene]-1,3-oxazol-5(4H)-one
which was used without further purification.
[0113] b) 1N NaOH (100 .mu.L) and H.sub.2O (500 .mu.L) is added to
a solution of
(4Z)-2-(2-furyl)-4-[(5-phenyl-2-furyl)methylene]-1,3-oxazol-5(4H)-one
(10 mg, 0.0327 mmol), prepared as described above, in acetone (1
mL). The reaction mixture is heated to 75.degree. C. for one hour
and then cooled to 25.degree. C.. The crude mixture is loaded onto
a QAX column, which was pre-treated with MeOH. After 2 minutes the
column is washed with MeOH and the product is eluted with 3%
HCl/MeOH. Subsequently, the column is washed with MeOH (2 mL) and
the combined washings are concentrated under reduced pressure to
provide 9.5 mg of
(2Z)-2-(2-furoylamino)-3-(5-phenyl-2-furyl)prop-2-enoic acid.
Example 12
N-{(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-hydroxybenzoyl)amino]prop-2-eno-
yl}glycine
[0114] ##STR36##
[0115] a) A suspension of 4-(2-bromophenoxy)benzaldehyde (0.35 g,
1.26 mmol), 2-hydroxy hippuric acid (0.22 g, 1.14 mmol) and sodium
acetate (0.12 g, 1.48 mmol) in acetic anhydride (1 mL) is heated to
60.degree. C. on an orbital shaker for one hour and is then cooled
to 0.degree. C. The reaction mixture is then concentrated under
reduced pressure at 45.degree. C. to afford a crude yellow solid.
This solid is washed with ice water (150 mL) and heptane (100 mL)
and then dried under vacuum at 40.degree. C. to provide 0.475 g of
2-{(4Z)-4-[4-(2-bromophenoxy)benzylidene]-5-oxo-4,5-dihydro-1,3-oxazol-2--
yl}phenyl acetate.
[0116] b) A portion of
2-{(4Z)-4-[4-(2-bromophenoxy)benzylidene]-5-oxo-4,5-dihydro-1,3-oxazol-2--
yl}phenyl acetate (0.10 g, 0.229 mmol), prepared as described
above, is suspended in DCM (10 mL) and treated with glycine ethyl
ester hydrochloride (67 m g, 0.48 mmol). The reaction is heated to
60.degree. C. for 4 hours and then concentrated. The resulting
solid is triturated with EtOAc to provide ethyl
N-{(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-hydroxybenzoyl)amino]prop-2-en-
oyl}glycinate, which is subsequently suspended in 1N NaOH (1 mL)
and ethanol (1 mL) and stirred at 25.degree. C. for 3 hours. The
ethanol is removed and several drops of concentrated HCl added and
a precipitate is formed. Filtration afforded 65 mg of
N-{(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-hydroxybenzoyl)amino]prop-2-en-
oyl}glycine.
Example 13
N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1-{[(2-hydroxyethyl)amino]carbonyl}et-
henyl)-2-hydroxybenzamide
[0117] ##STR37##
[0118] a) A suspension of 4-(2-chlorophenoxy)benzaldehyde (0.193 g,
0.83 mmol, 2-hydroxy hippuric acid (0.147 g, 0.75 mmol) and sodium
acetate (0.08 g, 0.975 mmol) in acetic anhydride (0.5 mL) is heated
to 60.degree. C. on an orbital shaker for one hour and is cooled to
room temperature. The reaction mixture is concentrated under
reduced pressure at 45.degree. C. to provide an orange solid. The
solid is washed with ice water (150 mL) and heptane (100 mL) and
dried under vacuum at 40.degree. C. to provide 0.32 g
2-{(4Z)-4-[4-(2-chlorophenoxy)benzylidene]-5-oxo-4,5-dihydro-1,3-oxazol-2-
-yl}phenyl acetate.
[0119] b)
2-{(4Z)-4-[4-(2-bromophenoxy)benzylidene]-5-oxo-4,5-dihydro-1,3-
-oxazol-2-yl}phenyl acetate (0.1 9, 0.23 mmol), prepared as
described above, was suspended in CH.sub.2Cl.sub.2 (10 mL) and was
treated with ethanol amine (40 .mu.L, 0.66 mmol). The reaction was
heated to 60.degree. C. for 3.5 hours and concentrated. The
magnesium sulfate and concentrated. The resulting residue was
suspended in acetone/1 N NaOH (3:1) and shaken for 1 hr. Acetone is
removed and the product extracted ethyl acetate. The organic layer
is dried over magnesium sulfate, concentrated and chromatographed
on a silica plug, eluting with heptane, 20% ethyl acetate/heptane,
50% ethyl acetate/heptane, ethyl acetate, and methanol (5 mL each).
The methanol fraction is concentrated and evaporated from Et.sub.2O
to provide 15 mg of
N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1-{[(2-hydroxyethyl)amino]carbonyl}e-
thenyl)-2-hydroxybenzamide as a yellow solid.
Example 14
[0120] Further examples of this invention include: [0121]
(2Z)-2-(benzoylamino)-3-{5-phenyl-2-furyl}prop-2-enoic acid; [0122]
(2Z)-2-(benzoylamino)-3-{5-[2-(trifluoromethyl)phenyl]-2-furyl}prop-2-eno-
ic acid; [0123]
(2Z)-2-(benzoylamino)-3-{5-[3-(trifluoromethyl)phenyl-2-furyl}prop-2-enoi-
c acid; [0124]
(2Z)-2-(benzoylamino)-3-{5-[4-(trifluoromethyl)phenyl]-2-furyl}prop-2-eno-
ic acid; [0125]
(2Z)-2-(benzoylamino)-3-(5-phenylthien-2-yl)prop-2-enoic acid;
[0126]
(2Z)-2-(benzoylamino)-3-[5-(4-fluorophenyl)-2-furyl]prop-2-enoic
acid; [0127]
(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)-2-furyl]prop-2-enoic
acid; [0128]
(2Z)-2-(benzoylamino)-3-[5-(3-chlorophenyl)-2-furyl]prop-2-enoic
acid; [0129]
(2Z)-2-(benzoylamino)-3-[5-(4-chlorophenyl)-2-furyl]prop-2-enoic
acid; [0130]
(2Z)-2-(benzoylamino)-3-[5-(3,4-dichlorophenyl)-2-furyl]prop-2-enoic
acid; [0131]
(2Z)-2-(benzoylamino)-3-{5-[4-(dimethylamino)phenyl]-2-furyl}prop-2-enoic
acid; [0132]
(2Z)-2-(benzoylamino)-3-{5-[4-(trifluoromethoxy)phenyl]-2-furyl}prop-2-en-
oic acid; [0133]
(2Z)-2-(benzoylamino)-3-[5-(1,1'-biphenyl-4-yl)-2-furyl]prop-2-enoic
acid; [0134]
(2Z)-2-(benzoylamino)-3-[5-(2-naphthyl)-2-furyl]prop-2-enoic acid;
[0135]
(2Z)-2-(benzoylamino)-3-[5-(3-fluorophenyl)-2-furyl]prop-2-enoic
acid; [0136]
(2Z)-2-(benzoylamino)-3-[5-(3-nitrophenyl)-2-furyl]prop-2-enoic
acid; [0137]
(2Z)-2-(benzoylamino)-3-[5-(2-nitrophenyl)-2-furyl]prop-2-enoic
acid; [0138] methyl
(2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)prop-2-enoate; [0139]
(2Z)-2-(benzoylamino)-3-[5-(4-cyanophenyl)-2-furyl]prop-2-enoic
acid; [0140]
(2Z)-2-(benzoylamino)-3-[5-(4-tert-butylphenyl)-2-furyl]prop-2-en-
oic acid; [0141]
(2Z)-3-{5-[4-(aminosulfonyl)phenyl]-2-furyl}-2-(benzoylamino)prop-2-enoic
acid; [0142]
(2Z)-2-(benzoylamino)-3-{5-[4-(methylthio)phenyl]-2-furyl}prop-2-enoic
acid; [0143]
(2Z)-3-[5-(1,3-benzodioxol-5-yl)-2-furyl]-2-(benzoylamino)prop-2-enoic
acid; [0144]
(2Z)-3-[5-(1-benzothien-2-yl)-2-furyl]-2-(benzoylamino)prop-2-enoic
acid; [0145]
(2Z)-2-(benzoylamino)-3-[5-(3,5-dibromophenyl)-2-furyl]prop-2-en-
oic acid; [0146]
(2Z)-2-(benzoylamino)-3-[5-(3-cyanophenyl)-2-furyl]prop-2-enoic
acid; [0147]
(2Z)-2-(benzoylamino)-3-{5-[4-(hydroxymethyl)phenyl]-2-furyl}prop-
-2-enoic acid; [0148]
(2Z)-2-(benzoylamino)-3-[5-(4-butylphenyl)-2-furyl]prop-2-enoic
acid; [0149]
(2Z)-2-(benzoylamino)-3-[5-(4-hydroxyphenyl)-2-furyl]prop-2-enoic
acid; [0150]
(2Z)-2-(benzoylamino)-3-{5-[4-(ethylsulfonyl)phenyl]-2-furyl}prop-2-enoic
acid; [0151]
(2Z)-2-(benzoylamino)-3-{5-[3-(trifluoromethoxy)phenyl]-2-furyl}prop-2-en-
oic acid; [0152]
(2Z)-2-(benzoylamino)-3-{5-[3-(hydroxymethyl)phenyl]-2-furyl}prop-2-enoic
acid; [0153]
(2Z)-3-[5-(1-benzofuran-2-yl)-2-furyl]-2-(benzoylamino)prop-2-enoic
acid; [0154]
(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-eno-
ic acid; [0155]
(2Z)-2-(benzoylamino)-3-(2'-chloro-1,1'-biphenyl-4-yl)prop-2-enoic
acid; [0156]
(2Z)-3-(1-benzofuran-2-yl)-2-(benzoylamino)prop-2-enoic acid;
[0157] (2Z)-2-(benzoylamino)-3-(1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0158]
(2Z)-2-(benzoylamino)-3-(5-phenyl-1,3-oxazol-2-yl)prop-2-enoic
acid; [0159]
(2Z)-2-(benzoylamino)-3-[5-(2,3-difluorophenyl)-2-furyl]prop-2-enoic
acid; [0160]
(2Z)-2-(benzoylamino)-3-[5-(2,3-dichlorophenyl)-2-furyl]prop-2-enoic
acid; [0161]
(2Z)-2-(benzoylamino)-3-[5-(2-methylphenyl)-2-furyl]prop-2-enoic
acid; [0162]
(2Z)-2-(benzoylamino)-3-[5-(2-ethoxyphenyl)-2-furyl]prop-2-enoic
acid; [0163]
(2Z)-3-{5-[3-(aminosulfonyl)phenyl]-2-furyl}-2-(benzoylamino)prop-2-enoic
acid; [0164]
(2Z)-2-(benzoylamino)-3-[5-(2-fluorophenyl)-2-furyl]prop-2-enoic
acid; [0165]
(2Z)-2-(benzoylamino)-3-[5-(2-methoxyphenyl)-2-furyl]prop-2-enoic
acid; [0166]
(2Z)-2-(benzoylamino)-3-[5-(2,3-dimethylphenyl)-2-furyl]prop-2-enoic
acid; [0167]
(2Z)-2-(benzoylamino)-3-[5-(2-methylphenyl)thien-2-yl]prop-2-enoic
acid; [0168]
(2Z)-3-[5-(2-aminophenyl)-2-furyl]-2-(benzoylamino)prop-2-enoic
acid; [0169] (2Z)-2-(benzoylamino)-3-(2-furyl)prop-2-enoic acid;
[0170] (2Z)-2-(benzoylamino)-3-(1,1'-biphenyl-4-yl)prop-2-enoic
acid; [0171]
(2Z)-2-(benzoylamino)-3-[5-(2,3-difluorophenyl)thien-2-yl]prop-2--
enoic acid; [0172]
(2Z)-2-(benzoylamino)-3-{5-[2-(trifluoromethoxy)phenyl]-2-furyl}prop-2-en-
oic acid; [0173]
(2Z)-2-(benzoylamino)-3-(4-phenylthien-2-yl)prop-2-enoic acid;
[0174]
(2Z)-2-(benzoylamino)-3-(5-pyridin-2-ylthien-2-yl)prop-2-enoic
acid; [0175]
(2Z)-2-(benzoylamino)-3-(5-phenylisoxazol-3-yl)prop-2-enoic acid;
[0176]
(2Z)-3-(5-phenyl-2-furyl)-2-[(pyridin-3-ylcarbonyl)amino]prop-2--
enoic acid; [0177]
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0178]
(2Z)-2-(2-furoylamino)-3-(5-phenyl-2-furyl)prop-2-enoic acid;
[0179]
(2Z)-2-[(3-methylbenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0180]
(2Z)-2-(benzoylamino)-3-[5-(2-fluorophenyl)thien-2-yl]prop-2-enoic
acid; [0181]
(2Z)-2-(benzoylamino)-3-[5-(2,5-difluorophenyl)thien-2-yl]prop-2--
enoic acid; [0182]
(2Z)-2-(benzoylamino)-3-{5-[2-(hydroxymethyl)phenyl]thien-2-yl}prop-2-eno-
ic acid; [0183]
(2Z)-2-(benzoylamino)-3-[5-(2-methoxyphenyl)thien-2-yl]prop-2-enoic
acid; [0184]
(2Z)-2-(benzoylamino)-3-(3-methyl-1-benzothien-2-yl)prop-2-enoic
acid; [0185]
(2Z)-2-[(2-methylbenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0186]
(2Z)-2-{[4-(acetylamino)benzoyl]amino}-3-(5-phenyl-2-furyl)prop-2-
-enoic acid; [0187]
(2Z)-2-[(4-methylbenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0188]
(2Z)-2-[(4-nitrobenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0189]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(pyridin-3-ylcarbonyl)amino]prop-
-2-enoic acid; [0190]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-hydroxybenzoyl)amino]prop-2-e-
noic acid; [0191]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-(2-furoylamino)prop-2-enoic
acid; [0192]
(2Z)-3-[5-(2-chlorophenyl)thien-2-y]-2-[(3-methylbenzoyl)amino]p-
rop-2-enoic acid; [0193]
(2Z)-2-(benzoylamino)-3-(5-phenyl-1,3-thiazol-2-yl)prop-2-enoic
acid; [0194]
(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)-1,3-thiazol-2-yl]prop-
-2-enoic acid; [0195]
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1,3-thiazol-5-yl]prop-2-enoic
acid; [0196]
(2Z)-2-(benzoylamino)-3-[4-(2-chlorophenyl)-1,3-thiazol-2-yl]prop-2-enoic
acid; [0197]
(2Z)-2-(benzoylamino)-3-[4-phenyl-5-(trifluoromethyl)thien-2-yl]prop-2-en-
oic acid; [0198]
(2Z)-2-[(4-aminobenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0199]
(2Z)-3-[5-(2-chlorophenyl)thien-2-a]-2-[(4-nitrobenzoyl)amino]pro-
p-2-enoic acid; [0200]
(2Z)-2-[(4-aminobenzoyl)amino]-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-eno-
ic acid; [0201]
(2Z)-3-[5-(2-chlorophenyl)thien-2-a]-2-[(2-methylbenzoyl)amino]prop-2-eno-
ic acid; [0202]
(2Z)-2-{[4-(acetylamino)benzoyl]amino}-3-[5-(2-chlorophenyl)thien-2-yl]pr-
op-2-enoic acid; [0203]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-methylbenzoyl)amino]prop-2-en-
oic acid; [0204]
(2Z)-2-[(2,5-dihydroxybenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0205]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2,5-dihydroxybenzoyl)amino]prop-
-2-enoic acid ; [0206]
(2Z)-2-(beta-alanylamino)-3-(5-phenyl-2-furyl)prop-2-enoic acid
trifluoroacetate; [0207]
(2Z)-2-[(3-hydroxybenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0208]
(2Z)-2-[(4-hydroxybenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0209]
(2Z)-2-(benzoylamino)-3-{5-[2-chloro-5-(trifluoromethyl)phenyl-2-furyl}pr-
op-2-enoic acid; [0210]
(2Z)-2-(benzoylamino)-3-{5-[2,6-dichloro-4-(trifluoromethyl)phenyl]-2-fur-
yl}prop-2-enoic [0211]
(2Z)-2-(benzoylamino)-3-(2'-chloro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0212]
(2Z)-2-(benzoylamino)-3-(1,1'-biphenyl-2-yl)prop-2-enoic acid;
[0213]
(2Z)-2-[(3,5-dihydroxybenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-e-
noic acid; [0214]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-hydroxybenzoyl)amino]prop-2-e-
noic acid; [0215]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(3-hydroxybenzoyl)amino]prop-2-e-
noic acid; [0216]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(3,5-dihydroxybenzoyl)amino]prop-
-2-enoic acid; [0217]
(2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]prop-2-enoic
acid; [0218]
(2Z)-2-(benzoylamino)-3-[4-(trifluoromethyl)phenyl]prop-2-enoic
acid; [0219] methyl
(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoate;
[0220]
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-[5-(2-methylphenyl)thien-2-yl]-
prop-2-enoic acid; [0221]
(2Z)-3-[5-(2,3-difluorophenyl)thien-2-yl]-2-[(2-hydroxybenzoyl)amino]prop-
-2-enoic acid; [0222]
(2Z)-2-[(3-nitrobenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0223]
(2Z)-2-[(3-aminobenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0224]
(2Z)-2-[(2-aminobenzoyl)amino]-3-(5-phenyl-2-furyl)prop-2-enoic
acid; [0225]
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-fluoro-1,1'-biphenyl-3-yl)pr-
op-2-enoic acid; [0226]
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-methoxy-1,1'-biphenyl-3-yl)prop-2-en-
oic acid; [0227]
(2Z)-2-(benzoylamino)-3-(2'-chloro-5,6-dimethoxy-1,1'-biphenyl-3-yl)prop--
2-enoic acid; [0228]
(2Z)-2-(benzoylamino)-3-(2',3'-difluoro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0229]
(2Z)-2-(benzoylamino)-3-(2'-chloro-4-fluoro-1,1'-biphenyl-3-yl)prop-2-eno-
ic acid; [0230]
(2Z)-2-(benzoylamino)-3-(2'-chloro-4-methoxy-1,1'-biphenyl-3-yl)prop-2-en-
oic acid; [0231]
(2Z)-3-(2'-chloro-6-fluoro-1,1'-biphenyl-3-yl)-2-[(2-hydroxybenzoyl)amino-
]prop-2-enoic acid; [0232]
(2Z)-2-(benzoylamino)-3-[4-chloro-3-(trifluoromethyl)phenyl]prop-2-enoic
acid; [0233] (2Z)-2-(benzoylamino)-3-(3-phenoxyphenyl)prop-2-enoic
acid; [0234] 2-(benzoylamino)-3,3-diphenylacrylic acid; [0235]
(2Z)-2-[(3-aminobenzoyl)amino]-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-eno-
ic acid; [0236]
(2Z)-2-[(2-aminobenzoyl)amino]-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-eno-
ic acid; [0237]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-nitrobenzoyl)amino]prop-2-eno-
ic acid; [0238]
(2Z)-3-(2'-chloro-1,1'-biphenyl-3-yl)-2-[(2-hydroxybenzoyl)amino]prop-2-e-
noic acid; [0239]
(2Z)-2-(benzoylamino)-3-(4-methyl-2-phenyl-1,3-thiazol-5-yl)prop-2-enoic
acid; [0240]
(2Z)-2-(benzoylamino)-3-[6-(2-chlorophenyl)pyridin-2-yl]prop-2-enoic
acid; [0241] (2Z)-2-(benzoylamino)-3-[2-(2-chlorophenyl)-1
H-imidazol-5-yl]prop-2-enoic acid; [0242]
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-hydroxy-1,1'-biphenyl-3-yl)prop-2-en-
oic acid; [0243]
(2Z)-2-(benzoylamino)-3-(1-methyl-1H-indol-2-yl)prop-2-enoic acid;
[0244] (2Z)-2-(benzoylamino)-3-(3-pyridin-2-ylphenyl)prop-2-enoic
acid; [0245]
(2Z)-2-(benzoylamino)-3-(3-pyridin-3-ylphenyl)prop-2-enoic acid;
[0246] (2Z)-2-(benzoylamino)-3-(3-pyridin-4-ylphenyl)prop-2-enoic
acid; [0247] (2Z)-2-(benzoylamino)-3-(4-phenoxyphenyl)prop-2-enoic
acid; [0248] (2Z)-2-(benzoylamino)-3-(2-phenoxyphenyl)prop-2-enoic
acid; [0249]
(2Z)-2-(benzoylamino)-3-[5-(phenylethynyl)thien-2-yl]prop-2-enoic
acid; [0250]
3-{5-[(Z)-2-(benzoylamino)-2-carboxyethenyl]-2-furyl}thiophene-2-carboxyl-
ic acid; [0251]
(2Z)-2-(benzoylamino)-3-{5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-
thien-2yl}prop-2-enoic acid; [0252]
(2Z)-2-(benzoylamino)-3-{5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-
thien-2-yl}prop-2-enoic acid; [0253]
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-{[(2-hydroxyethyl)amino]carbony-
l}ethenyl)benzamide; [0254]
N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-(morpholin-4-ylcarbonyl)ethenyl-
]benzamide; [0255]
(2Z)-2-(benzoylamino)-3-(2',4'-dichloro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0256]
(2Z)-2-(benzoylamino)-3-(2',5'-dichloro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0257]
(2Z)-2-(benzoylamino)-3-(2',4-dichloro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0258]
(2Z)-2-(benzoylamino)-3-[5-(2,5-dichlorophenyl)-2-furyl]prop-2-enoic
acid; [0259]
(2Z)-2-(benzoylamino)-3-{5-[2-chloro-4-(trifluoromethyl)phenyl]-2-furyl}p-
rop-2-enoic acid; [0260]
(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)pyridin-3-yl]prop-2-enoic
acid; [0261]
(2Z)-2-(benzoylamino)-3-(2-methyl-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0262]
2-[(Z)-2-(benzoylamino)-2-carboxyethenyl]-5-(4-chlorophenyl)-3-en-
oic acid; [0263]
(2Z)-2-(benzoylamino)-3-[4-(2-chlorophenoxy)phenyl]prop-2-enoic
acid; [0264] methyl
(2Z)-2-(benzoylamino)-3-[2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]prop-2-e-
noate; [0265]
(2Z)-2-(benzoylamino)-3-[2'-(trifluoromethyl)-1,1'-biphenyl-3-yl]prop-2-e-
noic acid; [0266]
N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-(piperidin-1-ylcarbonyl)ethenyl-
]benzamide; [0267]
N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-(piperazin-1-ylcarbonyl)ethenyl-
]benzamide; [0268] methyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoyl}gly-
cinate; [0269] methyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoyl}-be-
ta-alaninate; [0270]
(2Z)-2-(benzoylamino)-3-[4-(phenylthio)phenyl]prop-2-enoic acid;
[0271]
(2Z)-2-(benzoylamino)-3-[4-(phenylsulfonyl)phenyl]prop-2-enoic
acid;
[0272]
(2Z)-2-(benzoylamino)-3-(2-hydroxy-1,1'-biphenyl-3-yl)prop-2-enoi-
c acid; [0273]
(2Z)-2-(benzoylamino)-3-[4-phenoxy-2-(trifluoromethyl)phenyl]prop-2-enoic
acid; [0274]
(2Z)-2-(benzoylamino)-3-[4-phenoxy-3-(trifluoromethyl)phenyl]prop-2-enoic
acid; [0275]
(2Z)-2-(benzoylamino)-3-(3-cyano-4-phenoxyphenyl)prop-2-enoic acid;
[0276]
3-{5-[(Z)-2-(benzoylamino)-2-carboxyethenyl]-2-furyl}-4-methylthi-
ophene-2-carboxylic acid; [0277]
(2Z)-2-(benzoylamino)-3-[4-(benzyloxy)phenyl]prop-2-enoic acid;
[0278] (2Z)-2-(benzoylamino)-3-(2-morpholin-4-ylphenyl)prop-2-enoic
acid; [0279]
3'-[(Z)-2-(benzoylamino)-2-carboxyethenyl]-1,1'-biphenyl-2-carbox-
ylic acid; [0280] (2Z)-2-(benzoylamino)-3-(2'-cyano-1
1'-biphenyl-3-yl)prop-2-enoic acid; [0281]
N-{(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoyl}-be-
ta-alanine; [0282]
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-{[(3-hydroxypropyl)amino]carbon-
yl}ethenyl)benzamide; [0283]
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-{[(4-hydroxybutyl)amino]carbony-
l}ethenyl)benzamide; [0284]
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-{[(2,3-dihydroxypropyl)amino]ca-
rbonyl}ethenyl)benzamide; [0285]
N-{(Z)-1-{[bis(2-hydroxyethyl)amino]carbonyl}-2-[5-(2-chlorophenyl)thien--
2-yl]ethenyl}benzamide; [0286] ethyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoyl}gly-
cinate; [0287]
N-{(2Z)-2-(benzoylamino)-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-enoyl}gly-
cine; [0288] (2Z)-3-[4-(1
H-benzimidazol-1-yl)phenyl]-2-(benzoylamino)prop-2-enoic acid;
[0289]
(2Z)-2-(benzoylamino)-3-[4-(2-fluorophenoxy)phenyl]prop-2-enoic
acid; [0290]
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]prop-2-enoic
acid; [0291]
(2Z)-2-(benzoylamino)-3-[4-(2-chlorophenoxy)-3-methylphenyl]prop-2-enoic
acid; [0292]
(2Z)-2-(benzoylamino)-3-[4-(2-chlorophenoxy)-3-nitrophenyl]prop-2-enoic
acid; [0293]
(2Z)-2-(benzoylamino)-3-(3-pyrimidin-5-ylphenyl)prop-2-enoic acid;
[0294]
(2Z)-2-(benzoylamino)-3-[4-(2-cyanophenoxy)phenyl]prop-2-enoic
acid; [0295]
(2Z)-2-(benzoyamino)-3-[4-(2-chlorophenoxy)-2-(trifluoromethyl)phenyi]pro-
p-2-enoic acid;
[0296]
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorophenyl)thio]phenyl}prop-2-en-
oic acid; [0297]
2-{5-[(Z)-2-(benzoylamino)-2-carboxyethenyl]thien-2-yl}benzoic
acid; [0298]
(2Z)-2-(benzoylamino)-3-[5-(2-cyanophenyl)thien-2-yl]prop-2-enoic
acid; [0299]
(2Z)-2-(benzoylamino)-3-(3'-formyl-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0300]
N-[(Z)-1-[(2-hydroxyethyl)amino]carbonyl}-2-(5-phenyl-2-furyl)eth-
enyl]benzamide; [0301]
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1-{[(2-hydroxyethyl)amino]carbony-
l}ethenyl)-2-hydroxybenzamide; [0302]
N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1-{[(2-hydroxyethyl)amino]carbonyl}e-
thenyl)benzamide; [0303]
(2Z)-3-{4-[(2-chlorophenyl)thio]phenyl}-2-[(2-hydroxybenzoyl)amino]prop-2-
-enoic acid; [0304]
N-((Z)-2-{4-[(2-chlorophenyl)thio]phenyl}-1-{[(2-hydroxyethyl)amino]carbo-
nyl}ethenyl)benzamide; [0305]
N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1-{[(2-hydroxyethyl)amino]carbonyl}e-
thenyl)-2-hydroxybenzamide; [0306]
N-((Z)-2-{4-[(2-chlorophenyl)thio]phenyl}-1-{[(2-hydroxyethyl)amino]carbo-
nyl}ethenyl)-2-hydroxybenzamide; [0307]
(2Z)-2-(benzoylamino)-3-[4-(3-chlorophenoxy)phenyl]prop-2-enoic
acid; [0308]
(2Z)-2-(benzoylamino)-3-[3-chloro-4-(2-chlorophenoxy)phenyl]prop--
2-enoic acid; [0309]
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorobenzyl)oxy]phenyl}prop-2-enoic
acid; [0310]
(2Z)-2-(benzoylamino)-3-{5-[(2-chlorophenyl)thio]-2-furyl}prop-2-
-enoic acid; [0311]
(2Z)-2-(benzoylamino)-3-{5-[(2-chlorophenyl)thio]thien-2-yl}prop-2-enoic
acid; [0312]
(2Z)-2-(benzoylamino)-3-[4-(2-phenylethoxy)phenyl]prop-2-enoic
acid; [0313]
(2Z)-2-(benzoylamino)-3-[4-(2,3-dichlorophenoxy)phenyl]prop-2-eno-
ic acid; [0314]
(2Z)-2-(benzoylamino)-3-{4-[(2-bromophenyl)thio]phenyl}prop-2-enoic
acid; [0315]
(2Z)-2-(benzoylamino)-3-[4-(2-methoxyphenoxy)phenyl]prop-2-enoic
acid; [0316]
(2Z)-2-(benzoylamino)-3-[4-(2-ethylphenoxy)phenyl]prop-2-enoic
acid; [0317]
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-fluorophenoxy)phenyl]prop-2-
-enoic acid; [0318]
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-5-fluorophenoxy)phenyl]prop-2-enoic
acid; [0319]
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-chlorophenoxy)phenyl]prop-2-enoic
acid; [0320]
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)-3-fluorophenyl]prop-2-enoic
acid; [0321]
(2Z)-2-(benzoylamino)-3-{5-[(2-bromophenyl)thio]-2-furyl}prop-2-enoic
acid; [0322]
N-{(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-hydroxybenzoyl)amino]prop-2-en-
oyl}glycine; [0323]
N-{(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]prop-2-enoyl}glycine-
; [0324]
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1-{[(2-hydroxyethyl)amino]c-
arbonyl}ethenyl)benzamide; [0325]
(2Z)-3-(2'-amino-1,1'-biphenyl-3-yl)-2-(benzoylamino)prop-2-enoic
acid; [0326]
(2Z)-2-(benzoylamino)-3-(2'-hydroxy-1,1'-biphenyl-3-yl)prop-2-eno-
ic acid; [0327]
(2Z)-2-(benzoylamino)-3-(2'-nitro-1,1'-biphenyl-3-yl)prop-2-enoic
acid; [0328]
(2Z)-2-(benzoylamino)-3-[5-(2-nitrophenyl)thien-2-yl]prop-2-enoic
acid; [0329]
(2Z)-3-[5-(2-aminophenyl)thien-2-yl]-2-(benzoylamino)prop-2-enoic
acid; [0330]
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorophenyl)amino]phenyl}prop-2-e-
noic acid; [0331]
(2Z)-2-(benzoylamino)-3-[4-(2-methylphenoxy)phenyl]prop-2-enoic
acid; [0332]
(2Z)-2-(benzoylamino)-3-[4-(2-isopropoxyphenoxy)phenyl]prop-2-eno-
ic acid; [0333]
(2Z)-2-(benzoylamino)-3-[4-(2-iodophenoxy)phenyl]prop-2-enoic acid;
[0334]
(2Z)-2-(benzoylamino)-3-{5-[(2-bromophenyi)thio]thien-2-yl}prop-2-
-enoic acid; [0335]
(2Z)-2-(benzoylamino)-3-{2-[(2-bromophenyl)thio]-1,3-thiazol-4-yl}prop-2--
enoic acid; [0336]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-methoxybenzoyl)amino]prop-2-e-
noic acid; [0337]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-{[4-(trifluoromethyl)benzoyl]amin-
o}prop-2-enoic acid; [0338]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(3,4,5-trimethoxybenzoyl)amino]p-
rop-2-enoic acid; [0339]
(2Z)-2-[(4-chlorobenzoyl)amino]-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-en-
oic acid; [0340]
(2Z)-2-[(4-bromobenzoyl)amino]-3-[5-(2-chlorophenyl)thien-2-yl]prop-2-eno-
ic acid; [0341]
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-{[3-(trifluoromethyl)benzoyl]amin-
o}prop-2-enoic acid; [0342] methyl
3'-[(1Z)-2-(benzoylamino)-3-methoxy-3-oxoprop-1-enyl]-1,1'-biphenyl-2-car-
boxylate; [0343] methyl
(2Z)-2-(benzoylamino)-3-(2'-cyano-1,1'-biphenyl-3-yl)prop-2-enoate;
[0344] methyl
2-{5-[(1Z)-2-(benzoylamino)-3-methoxy-3-oxoprop-1-enyl]thien-2-yl}benzoat-
e; [0345] methyl
(2Z)-2-(benzoylamino)-3-[5-(2-nitrophenyl)thien-2-yl]prop-2-enoate;
[0346] methyl
(2Z)-2-(benzoylamino)-3-(2'-nitro-1,1'-biphenyl-3-yl)prop-2-enoate;
[0347] methyl
(2Z)-3-[2'-(acetyloxy)-1,1'-biphenyl-3-yl]-2-(benzoylamino)prop-2-enoate;
[0348] N-[4-(2-bromophenoxy)phenyl]benzamide; [0349]
(2Z)-2-(benzoylamino)-3-{4-[2-chloro-3-(trifluoromethyl)phenoxy]phenyl}pr-
op-2-enoic acid; [0350]
(2Z)-2-(benzoylamino)-3-{4-[2-(methylthio)phenoxy]phenyl}prop-2-enoic
acid; [0351]
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-cyanophenoxy)phenyl]prop-2-enoic
acid; [0352]
(2Z)-2-(benzoylamino)-3-[4-(2-bromobenzoyl)phenyl]prop-2-enoic
acid; [0353]
(2Z)-2-(benzoylamino)-3-{4-[(2-chlorophenyl)(methyl)amino]phenyl}-
prop-2-enoic acid; [0354]
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-methylphenoxy)phenyl]prop-2-enoic
acid; [0355]
(2Z)-2-(benzoylamino)-3-[4-(2-cyclopentylphenoxy)phenyl]prop-2-enoic
acid; [0356]
(2Z)-2-(benzoylamino)-3-{4-[2-(trifluoromethoxy)phenoxy]phenyl}prop-2-eno-
ic acid; [0357]
(2Z)-2-(benzoylamino)-3-[4-(1,1'-biphenyl-2-yloxy)phenyl]prop-2-enoic
acid; [0358]
(2Z)-2-(benzoylamino)-3-[4-(2,3-difluorophenoxy)phenyl]prop-2-enoic
acid; [0359]
(2Z)-2-(benzoylamino)-3-[4-(2-isopropylphenoxy)phenyl]prop-2-eno-
ic acid; [0360]
(2Z)-2-(benzoylamino)-3-[4-(2-chloro-4-methoxyphenoxy)phenyl]prop-2-enoic
acid; [0361]
(2Z)-2-(benzoylamino)-3-[4-(2-nitrophenoxy)phenyl]prop-2-enoic
acid; [0362] (2Z)-2-(benzoylamino)-3-{4-[(
1-bromo-2-naphthyl)oxy]phenyl}prop-2-enoic acid; [0363]
(2Z)-2-(benzoylamino)-3-(4-{[4-nitro-2-(trifluoromethyl)cyclohexa-1,5-die-
n-1-yl]oxy}phenyl)prop-2-enoic acid; [0364]
(2Z)-3-(4-{[4-amino-2-(trifluoromethyl)cyclohexa-1,5-dien-1-yl]oxy}phenyl-
)-2-(benzoylamino)prop-2-enoic acid; [0365]
(2Z)-2-(benzoylamino)-3-{4-[2-(trifluoromethyl)phenoxy]phenyl}prop-2-enoi-
c acid; [0366]
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-hydroxybenzoyl)amino]prop-2-enoic
acid; [0367]
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-[4-(2-iodophenoxy)phenyl]prop-2-enoic
acid; [0368]
2-hydroxy-N-{(Z)-1-{[(2-hydroxyethyl)amino]carbonyl}-2-[4-(2-iodophenoxy)-
phenyl]ethenyl}benzamide; [0369]
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)-3-nitrophenyl]prop-2-enoic
acid; [0370]
(2Z)-2-(benzoylamino)-3-[4-(phenoxymethyl)phenyl]prop-2-enoic acid;
[0371]
(2Z)-2-(benzoylamino)-3-[4-(pyridin-2-ylmethoxy)phenyl]prop-2-eno-
ic acid; [0372]
(2Z)-2-(benzoylamino)-3-{4-[(2-fluorobenzyl)oxy]phenyl}prop-2-enoic
acid; [0373]
(2Z)-2-(benzoylamino)-3-(4-{[3-(trifluoromethyl)benzyl]oxy}pheny-
l)prop-2-enoic acid [0374]
(2Z)-3-[3-amino-4-(2-bromophenoxy)phenyl]-2-(benzoylamino)prop-2-enoic
acid; [0375] methyl
(2Z)-2-(benzoylamino)-3-[4-(2-bromophenoxy)phenyl]prop-2-enoate;
[0376]
2-[({(Z)-2-[4-(2-bromophenoxy)phenyl]-1-carboxyethenyl}amino)carbonyl]ben-
zoic acid; [0377]
(2Z)-2-(benzoylamino)-3-{4-[(4-cyanobenzyl)oxy]phenyl}prop-2-enoic
acid; [0378]
(2Z)-2-(benzoylamino)-3-[4-(pyridin-3-ylmethoxy)phenyl]prop-2-eno-
ic acid; [0379]
(2Z)-2-(benzoylamino)-3-[4-(pyridin-4-ylmethoxy)phenyl]prop-2-enoic
acid; [0380]
(2Z)-2-(benzoylamino)-3-(4-{[4-(trifluoromethyl)benzyl]oxy}pheny-
l)prop-2-enoic acid; [0381]
(2Z)-2-(benzoylamino)-3-{4-[(4-fluorobenzyl)oxy]phenyl}prop-2-enoic
acid; [0382]
(2Z)-2-(benzoylamino)-3-{4-[(3-nitrobenzyl)oxy]phenyl}prop-2-eno-
ic acid; [0383]
(2Z)-2-(benzoylamino)-3-{4-[(4-methylbenzyl)oxy]phenyl}prop-2-enoic
acid; [0384]
(2Z)-2-(benzoylamino)-3-{4-[(4-chlorobenzyl)oxy]phenyl}prop-2-en-
oic acid; [0385]
N-{(Z)-1-(aminocarbonyl)-2-[4-(2-bromophenoxy)phenyl]ethenyl}benzamide;
[0386] (2Z)-2-(benzoylamino)-3-[3-(benzyloxy)phenyl]prop-2-enoic
acid; [0387]
(2Z)-2-[benzoyl(methyl)amino]-3-[4-(2-bromophenoxy)phenyl]prop-2--
enoic acid; [0388]
(2Z)-2-(benzoylamino)-3-[3-(4-chlorophenoxy)phenyl]prop-2-enoic
acid; [0389]
(2Z)-2-(benzoylamino)-3-[3-(4-methylphenoxy)phenyl]prop-2-enoic
acid; [0390]
(2Z)-2-(benzoylamino)-3-[3-(4-methoxyphenoxy)phenyl]prop-2-enoic
acid; [0391]
(2Z)-2-(benzoylamino)-3-{3-[(2-chlorobenzyl)oxy]phenyl}prop-2-eno-
ic acid; [0392]
(2Z)-2-(benzoylamino)-3-{4-[(3-methoxybenzyl)oxy]phenyl}prop-2-enoic
acid; [0393]
(2Z)-2-(benzoylamino)-3-{4-[(3-chlorobenzyl)oxy]phenyl}prop-2-enoic
acid; [0394]
(2Z)-2-(benzoylamino)-3-(4-{[3-(trifluoromethoxy)benzyl]oxy}phen-
yl)prop-2-enoic acid; [0395]
(2Z)-2-(benzoylamino)-3-[3-(2-chlorophenoxy)phenyl]prop-2-enoic
acid; [0396]
(2Z)-2-(benzoylamino)-3-[3-(2-bromophenoxy)phenyl]prop-2-enoic
acid; [0397]
(2Z)-2-(benzoylamino)-3-[3-(2-chloro-4-nitrophenoxy)phenyl]prop-2-enoic
acid; [0398]
(2Z)-2-(benzoylamino)-3-{4-[(3-methylbenzyl)oxy]phenyl}prop-2-enoic
acid; [0399]
(2Z)-2-(benzoylamino)-3-[4-(2-tert-butylphenoxy)phenyl]prop-2-en-
oic acid; [0400]
(2Z)-2-(benzoylamino)-3-(4-[(3-fluorobenzyl)oxy]phenyl}prop-2-enoic
acid; [0401]
(2Z)-2-(benzoylamino)-3-{4-[(3-cyanobenzyl)oxy]phenyl}prop-2-eno-
ic acid; [0402]
(2Z)-2-(benzoylamino)-3-{3-[3-(trifluoromethyl)phenoxy]phenyl}prop-2-enoi-
c acid; [0403]
(2Z)-2-(benzoylamino)-3-[3-(4-tert-butylphenoxy)phenyl]prop-2-enoic
acid.
Example 15
[0403] Evaluation of Polymerase Activity
[0404] Compounds of the present invention are evaluated for
inhibition of HCV NS5b RNA dependent RNA polymerase activity in
assays comprised of a suitable buffer (e.g. 20 mM Tris-HCl pH 7.6),
primed or unprimed RNA templates, GTP, ATP, CTP, and UTP,
MnCl.sub.2 or MgCl.sub.2, and reducing agent such as 10 mM
dithiothreitol or 2-mercaptoethanol. The assay buffer may contain
salts such as ammonium acetate, KCl, or NaCl, and nonionic or
zwitterionic detergents such as Tween or CHAPS. The incorporation
of nucleotides into the complementary RNA strand may be monitored
by the incorporation of radiolabeled NTP (e.g. .sup.3H labeled
GTP). Suitable RNA templates for de novo initiation in the presence
of 20-50 .mu.M GTP or ATP are the homopolymers poly rC and poly rU,
respectively. Heteropolymer RNA templates with 1-3 cytidine (C)
bases or 1-3 uridine (U) bases at the 3' terminus of the template
may also be used for de novo initiation. Primed RNA templates such
as poly rC primed with oligo rG or oligo dG, and poly rA primed
with oligo rU may also be used to detect polymerase activity. The
primers may be any length greater than 10 bases. A biotin residue
may be added to the 5' end of the template or the 5' end of the
primer to capture the template and the newly synthesized,
complementary strand on avidin coated spheres. One embodiment of
this technology consists of a mixture of NS5b polymerase, a poly rC
RNA template primed with 5' biotinylated oligo rG, 20 mM Tris HCl
pH 7.6, 100 mM ammonium acetate, 10 mM dithiothreitol, 2 mM CHAPS,
1 mM MgCl.sub.2, and 150-200 nM .sup.3H labeled GTP. Test compounds
(inhibitors) may be incorporated in the reaction mixture with up to
10% DMSO. The reaction is run for various times (1-180 minutes) at
22-37.degree. C., and stopped by the addition of 10-140 mM EDTA.
Scintillation Proximity Assay avidin-coated beads (Amersham
Pharmacia Biotech) are added to capture the ds RNA product; or the
reaction mixtures may be transferred to avidin coated Flash Plates
(Perkin Elmer Life Sciences). The incorporation of radiolabeled GTP
into the complementary strand is measured in 96, 384, or 1536 well
plates in scintillation counters such as the Wallac Microbeta and
Packard TopCount.
[0405] A substantial number of the compounds exhibited IC50 values
ranging from less than 1 to about 30 .mu.M or more. In Table 2, the
inhibitory activity of representative examples is provided.
Activity is listed in Table 2 as +++ if the concentration for 50%
inhibition is <10 .mu.M, ++ if activity is 11-30 .mu.M and + if
activity is >30 .mu.M. TABLE-US-00002 TABLE 2 NS5B Inhibitory
Compound Activity 1 +++ 2 +++ 3 ++ 4 +++ 5 ++ 6 ++ 7 + 8 +++ 9 +++
10 +++ 11 + 12 + 13 +++ 14 ++ 15 ++ 16 +++ 17 + 18 +++ 19 + 20
+
[0406] Yet other compounds of this invention are illustrated in
Table 3. TABLE-US-00003 Compound Number Structure Name 1. ##STR38##
(2Z)-2-(benzoylamino)-3-[5-(2- chlorophenyl)thien-2-yl]prop-2-enoic
acid; 2. ##STR39## (2Z)-3-(5-phenyl-2-furyl)-2-[(pyridin-3-
ylcarbonyl)amino]prop-2-enoic acid; 3. ##STR40##
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 4. ##STR41## (2Z)-2-(2-furoylamino)-3-(5-phenyl-2-
furyl)prop-2-enoic acid; 5. ##STR42##
(2Z)-2-[(3-methylbenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 6. ##STR43## (2Z)-2-{[4-(acetylamino)benzoyl]amino}-3-
(5-phenyl-2-furyl)prop-2-enoic acid; 7. ##STR44##
(2Z)-2-[(4-methylbenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 8. ##STR45## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(pyridin-3-ylcarbonyl)amino]prop-2-enoic acid; 9. ##STR46##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-
hydroxybenzoyl)amino]prop-2-enoic acid; 10. ##STR47##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-(2-
furoylamino)prop-2-enoic acid; 11. ##STR48##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
methylbenzoyl)amino]prop-2-enoic acid; 12. ##STR49##
(2Z)-2-[(4-aminobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 13. ##STR50## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
nitrobenzoyl)amino]prop-2-enoic acid; 14. ##STR51##
(2Z)-2-[(4-aminobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 15. ##STR52##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-
methylbenzoyl)amino]prop-2-enoic acid; 16. ##STR53##
(2Z)-2-{[4-(acetylamino)benzoyl]amino}-3-
[5-(2-chlorophenyl)thien-2-yl]prop-2-enoic acid; 17. ##STR54##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
methylbenzoyl)amino]prop-2-enoic acid; 18. ##STR55##
(2Z)-2-[(2,5-dihydroxybenzoyl)amino]-3-
(5-phenyl-2-furyl)prop-2-enoic acid; 19. ##STR56##
(2Z)-3-[5-(2-chlorophenyi)thien-2-yl]-2-
[(2,5-dihydroxybenzoyl)amino]prop-2- enoic acid; 20. ##STR57##
(2Z)-2-[(3-hydroxybenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 21. ##STR58## (2Z)-2-[(4-hydroxybenzoyl)amino]-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 22. ##STR59##
(2Z)-2-[(3,5-dihydroxybenzoyl)amino]-3-
(5-phenyl-2-furyl)prop-2-enoic acid; 23. ##STR60##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
hydroxybenzoyl)amino]prop-2-enoic acid; 24. ##STR61##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(3-
hydroxybenzoyl)amino]prop-2-enoic acid; 25. ##STR62##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(3,5-dihydroxybenzoyl)amino]prop-2- enoic acid; 26. ##STR63##
(2Z)-2-[(3-nitrobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 27. ##STR64## (2Z)-2-[(3-aminobenzoyl)amino]-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 28. ##STR65##
(2Z)-2-[(2-aminobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 29. ##STR66## (2Z)-2-[(3-aminobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 30. ##STR67##
(2Z)-2-[(2-aminobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 31. ##STR68##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-
nitrobenzoyl)amino]prop-2-enoic acid; 32. ##STR69##
(2Z)-3-(2'-chloro-1,1'-biphenyl-3-yl)-2-[(2-
hydroxybenzoyl)amino]prop-2-enoic acid; 33. ##STR70##
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl) benzamide; 34. ##STR71##
N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- (morpholin-4-
ylcarbonyl)ethenyl]benzamide; 35. ##STR72##
N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- (piperidin-1-
ylcarbonyl)ethenyl]benzamide; 36. ##STR73## methyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoyl}- beta-alaninate; 37.
##STR74## N-{(2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoyl}- beta-alanine; 38. ##STR75##
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- {[(3-
hydroxypropyl)amino]carbonyl}ethenyl) benzamide; 39. ##STR76##
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- {[(4-
hydroxybutyl)amino]carbonyl}ethenyl) benzamide; 40. ##STR77##
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- {[(2,3-
dihydroxypropyl)amino]carbonyl}ethenyl) benzamide; 41. ##STR78##
N-{(Z)-1-{[bis(2- hydroxyethyl)amino]carbonyl}-2-[5-(2-
chlorophenyl)thien-2- yl]ethenyl}benzamide; 42. ##STR79## ethyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2- chlorophenyl)thien-2-yl]prop-2-
enoyl}glycinate; 43. ##STR80## N-{(2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2- enoyl}glycine; 44. ##STR81##
N-[(Z)-1-{[(2- hydroxyethyl)amino]carbonyl}-2-(5-
phenyl-2-furyl)ethenyl]benzamide; 45. ##STR82##
N-((Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2- hydroxybenzamide; 46.
##STR83## N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl) benzamide; 47. ##STR84##
(2Z)-3-{4-[(2-chlorophenyl)thio]phenyl)-2-
[(2-hydroxybenzoyl)amino]prop-2-enoic acid; 48. ##STR85##
N-((Z)-2-{4-[(2-chlorophenyl)thio]phenyl)- 1-{[(2-
hydroxyethyl)amino]carbonyl}ethenyl) benzamide; 49. ##STR86##
N-((Z)-2-[4-(2-chlorophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2- hydroxybenzamide; 50.
##STR87## N-((Z)-2-{4-[(2-chlorophenyl)thio]phenyl)- 1-{[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2- hydroxybenzamide; 51.
##STR88## N-{(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2-hydroxybenzoyl)amino]prop-2- enoyl}glycine; 52. ##STR89##
N-{(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)phenyl]prop-2-
enoyl}glycine; 53. ##STR90## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1-
{[(2- hydroxyethyl)amino]carbonyl}ethenyl) benzamide; 54. ##STR91##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
methoxybenzoyl)amino]prop-2-enoic acid; 55. ##STR92##
(2Z)-2-[(4-chlorobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 56. ##STR93##
(2Z)-2-[(4-bromobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 57. ##STR94##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-{[3-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 58. ##STR95##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
hydroxybenzoyl)amino]prop-2-enoic acid; 59. ##STR96##
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 60. ##STR97##
2-hydroxy-N-{(Z)-1-{[(2- hydroxyethyl)amino]carbonyl}-2-[4-(2-
iodophenoxy)phenyl]ethenyl}benzamide; 61. ##STR98##
2-[({(Z)-2-[4-(2-bromophenoxy)phenyl]-1-
carboxyethenyl}amino)carbonyl]benzoic acid; 62. ##STR99##
N-[(E)-2-bromo-2-[5-(2- chlorophenyl)thien-2-yl]-1-(piperidin-1-
ylcarbonyl)ethenyl]benzamide; 63. ##STR100##
2-hydroxy-N-((Z)-1-{[(2- hydroxyethyl)amino]carbonyl}-2-{4-[(3-
methoxybenzyl)oxy]phenyl}ethenyl) benzamide; 64. ##STR101##
N-((Z)-{[(2- hydroxyethyl)amino]carbonyl}-2-{4-[(3-
methoxybenzyl)oxy]phenyl}ethenyl) benzamide; 65. ##STR102##
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-{4-
[(3-methoxybenzyl)oxy]phenyl}prop-2- enoic acid; 66. ##STR103##
(2Z)-2-[(2-bromobenzoyl)amino]-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 67. ##STR104##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
fluorobenzoyl)amino]prop-2-enoic acid; 68. ##STR105##
(2Z)-2-[(2-fluorobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 69. ##STR106## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(2,4-difluorobenzoyl)amino]prop-2-enoic acid; 70. ##STR107##
(2Z)-2-[(2,6-difluorobenzoyl)amino]-3-{4-
[(3-methoxybenzyl)oxy]phenyl}prop-2- enoic acid; 71. ##STR108##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2,6-difluorobenzoyl)amino]prop-2-enoic acid; 72. ##STR109##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(pentafluorobenzoyl)amino]prop-2-enoic acid; 73. ##STR110##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
chlorobenzoyl)amino]prop-2-enoic acid; 74. ##STR111##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2,4-dichlorobenzoyl)amino]prop-2-enoic acid; 75. ##STR112##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
fluorobenzoyl)amino]prop-2-enoic acid; 76. ##STR113##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(2-
fluorobenzoyl)amino]prop-2-enoic acid; 77. ##STR114##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2,4-difluorobenzoyl)amino]prop-2-enoic acid; 78. ##STR115##
(2Z)-2-[(2-fluorobenzoyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl)prop-2-enoic acid; 79. ##STR116##
(2Z)-2-[(2-bromobenzoyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 80. ##STR117##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- {[(6-chloropyridin-3-
yl)carbonyl]amino}prop-2-enoic acid;
81. ##STR118## (2Z)-2-[(2,4-difluorobenzoyl)amino]-3-{4-
[(3-methoxybenzyl)oxy]phenyl}prop-2- enoic acid; 82. ##STR119## 83.
##STR120## 2-fluoro-N-((Z)-1-{[(2-
hydroxyethyl)amino]carbonyl)-2-{4-[(3-
methoxybenzyl)oxy]phenyl}ethenyl) benzamide; 84. ##STR121##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-3- fluorobenzamide; 85.
##STR122## N-((Z)-2-(4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2- chlorobenzamide; 86.
##STR123## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-6- chloronicotinamide; 87.
##STR124## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2- fluorobenzamide; 88.
##STR125## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyethyl)amino]carbonyl}ethenyl)-2,4- difluorobenzamide; 89.
##STR126## N-{(Z)-(anilinocarbonyl-2-[4-(2-
bromophenoxy)phenyl]ethenyl}-2- fluorobenzamide; 90. ##STR127##
N-{(Z)-2-[4-(2-bromophenoxy)phenyl]-1-
[(pyridin-2-ylamino)carbonyl]ethenyl}-2- fluorobenzamide; 91.
##STR128## N-[(Z)-2-[4-(2-bromophenoxy)phenyl]-1- ({[2-
(dimethylamino)ethyl]amino}carbonyl) ethenyl]-3-fluorobenzamide;
92. ##STR129## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1-
{[(4-morpholin-4- ylphenyl)amino]carbonyl}ethenyl)benzamide; 93.
##STR130## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(4-
hydroxyphenyl)amino]carbonyl}ethenyl) benzamide; 94. ##STR131##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(pyridin-2-
ylmethyl)amino]carbonyl}vinyl)benzamide 95. ##STR132##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
fluorobenzyl)amino]carbonyl}vinyl) benzamide 96. ##STR133##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(3-
fluorobenzyl)amino]carbonyl}vinyl) benzamide 97. ##STR134##
2-({(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)phenyl]prop-2-
enoyl}amino)benzoic acid; 98. ##STR135##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(2-
hydroxyphenyl)amino]carbonyl}vinyl) benzamide; 99. ##STR136##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(3-
hydroxyphenyl)amino]carbonyl}vinyl) benzamide; 100. ##STR137##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(pyridin-4-
ylmethyl)amino]carbonyl}vinyl)benzamide; 101. ##STR138##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(pyridin-3-
ylmethylamino]carbonyl}vinyl)benzamide; 102. ##STR139##
N-{(Z)-2-[4-(2-bromophenoxy)phenyl]-1- [(pyridin-3-
ylamino)carbonyl]vinyl}benzamide; 103. ##STR140##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1- {[(1-
naphthylmethyl)amino]carbonyl}vinyl) benzamide; 104. ##STR141##
(2Z)-2-(benzoylamino)-3-{5-[2-
(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 105.
##STR142## (2Z)-2-(benzoylamino)-3-{5-[3-
(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 106.
##STR143## (2Z)-2-(benzoylamino)-3-{5-[4-
(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 107.
##STR144## (2Z)-2-(benzoylamino)-3-(5-phenylthien-
2-yl)prop-2-enoic acid; 108. ##STR145##
(2Z)-2-(benzoylamino)-3-[5-(4- fluorophenyl)-2-furyl]prop-2-enoic
acid; 109. ##STR146## (2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)-2-furyl]prop-2-enoic acid; 110. ##STR147##
(2Z)-2-(benzoylamino)-3-[5-(3- chlorophenyl)-2-furyl]prop-2-enoic
acid; 111. ##STR148## (2Z)-2-(benzoylamino)-3-[5-(4-
chlorophenyl)-2-furyl]prop-2-enoic acid; 112. ##STR149##
(2Z)-2-(benzoylamino)-3-[5-(3,4-
dichlorophenyl)-2-furyl]prop-2-enoic acid; 113. ##STR150##
(2Z)-2-(benzoylamino)-3-{5-[4-
(dimethylamino)phenyl]-2-furyl)prop-2- enoic acid; 114. ##STR151##
(2Z)-2-(benzoylamino)-3-{5-[4-
(trifluoromethoxy)phenyl]-2-furyl}prop-2- enoic acid; 115.
##STR152## (2Z)-2-(benzoylamino)-3-[5-(1,1'-biphenyl-
4-yl)-2-furyl]prop-2-enoic acid; 116. ##STR153##
(2Z)-2-(benzoylamino)-3-[5-(2-naphthyl)- 2-furyl]prop-2-enoic acid;
117. ##STR154## (2Z)-2-(benzoylamino)-3-[5-(3-
fluorophenyl)-2-furyl]prop-2-enoic acid; 118. ##STR155##
(2Z)-2-(benzoylamino)-3-[5-(3- nitrophenyl)-2-furyl]prop-2-enoic
acid; 119. ##STR156## (2Z)-2-(benzoylamino)-3-[5-(2-
nitrophenyl)-2-furyl]prop-2-enoic acid; 120. ##STR157## methyl
(2Z)-2-(benzoylamino)-3-(5- phenyl-2-furyl)prop-2-enoate; 121.
##STR158## (2Z)-2-(benzoylamino)-3-[5-(4-
cyanophenyl)-2-furyl]prop-2-enoic acid; 122. ##STR159##
(2Z)-2-(benzoylamino)-3-[5-(4-tert-
butylphenyl)-2-furyl]prop-2-enoic acid; 123. ##STR160##
(2Z)-3-{5-[4-(aminosulfonyl)phenyl]-2-
furyl}-2-(benzoylamino)prop-2-enoic acid; 124. ##STR161##
(2Z)-2-(benzoylamino)-3-{5-[4-
(methylthio)phenyll-2-furyl}prop-2-enoic acid; 125. ##STR162##
(2Z)-2-(benzoylamino)-3-(5-bromo-2- furyl)prop-2-enoic acid; 126.
##STR163## (2Z)-3-[5-(1,3-benzodioxol-5-yl)-2-furyl]-2-
(benzoylamino)prop-2-enoic acid; 127. ##STR164##
(2Z)-3-{5(1-benzothien-2-yl)-2-furyl]-2- (benzoylamino)prop-2-enoic
acid; 128. ##STR165## (2Z)-2-(benzoylamino)-3-[5-(3,5-
dibromophenyl)-2-furyl]prop-2-enoic acid; 129. ##STR166##
(2Z)-2-(benzoylamino)-3-[5-(3- cyanophenyl)-2-furyl]prop-2-enoic
acid; 130. ##STR167## (2Z)-2-(benzoylamino)-3-{5-[4-
(hydroxymethyl)phenyl]-2-furyl}prop-2- enoic acid; 131. ##STR168##
(2Z)-2-(benzoylamino)-3-[5-(4- butylphenyl)-2-furyl]prop-2-enoic
acid; 132. ##STR169## (2Z)-2-(benzoylamino)-3-[5-(4-
hydroxyphenyl)-2-furyl]prop-2-enoic acid; 133. ##STR170##
(2Z)-2-(benzoylamino)-3-{5-[4-
(ethylsulfonyl)phenyl]-2-furyl}prop-2-enoic acid; 134. ##STR171##
(2Z)-2-(benzoylamino)-3-[5-[3-
(trifluoromethoxy)phenyl]-2-furyl)prop-2- enoic acid; 135.
##STR172## (2Z)-2-(benzoylamino)-3-{5-[3-
(hydroxymethyl)phenyl]-2-furyl}prop-2- enoic acid; 136. ##STR173##
(2Z)-3-[5(1-benzofuran-2-yl)-2-furyl]-2- (benzoylamino)prop-2-enoic
acid; 137 ##STR174## (2Z)-2-(benzoylamino)-3-(2'-chloro-1,1'-
biphenyl-4-yl)prop-2-enoic acid; 138. ##STR175##
(2Z)-3-(1-benzofuran-2-yl)-2- (benzoylamino)prop-2-enoic acid; 139.
##STR176## (2Z)-2-(benzoylamino)-3-(1,1'-biphenyl-3-
yl)prop-2-enoic acid; 140. ##STR177##
(2Z)-2-(benzoylamino)-3-(5-phenyl-1,3- oxazol-2-yl)prop-2-enoic
acid; 141. ##STR178## (2Z)-2-(benzoylamino)-3-[5-(2,3-
difluorophenyl)-2-furyl]prop-2-enoic acid; 142. ##STR179##
(2Z)-2-(benzoylamino)-3-[5-(2,3-
dichlorophenyl)-2-furyl]prop-2-enoic acid; 143. ##STR180##
(2Z)-2-(benzoylamino)-3-[5-(2- methylphenyl)-2-furyl]prop-2-enoic
acid; 144. ##STR181## (2Z)-2-(benzoylamino)-3-[5-(2-
ethoxyphenyl)-2-furyl]prop-2-enoic acid; 145. ##STR182##
(2Z)-3-{5-[3-(aminosulfonyl)phenyl]-2-
furyl}-2-(benzoylamino)prop-2-enoic acid; 146. ##STR183##
(2Z)-2-(benzoylamino)-3-[5-(2- fluorophenyl)-2-furyl]prop-2-enoic
acid; 147. ##STR184## (2Z)-2-(benzoylamino)-3-[5-(2-
methoxyphenyl)-2-furyl]prop-2-enoic acid; 148. ##STR185##
(2Z)-2-(benzoylamino)-3-[5-(2,3-
dimethylphenyl)-2-furyl]prop-2-enoic acid; 149. ##STR186##
(2Z)-2-(benzoylamino)-3-[5-(2- methylphenyl)thien-2-yl]prop-2-enoic
acid; 150. ##STR187## (2Z)-3-[5-(2-aminophenyl)-2-furyl]-2-
(benzoylamino)prop-2-enoic acid; 151. ##STR188##
(2Z)-2-(benzoylamino)-3-(2-furyl)prop-2- enoic acid; 152.
##STR189## (2Z)-2-(benzoylamino)-3-(1,1'-biphenyl-4-
yl)prop-2-enoic acid; 153. ##STR190##
(2Z)-2-(benzoylamino)-3-[5-(2,3-
difluorophenyl)thien-2-yl]prop-2-enoic acid; 154. ##STR191##
(2Z)-2-(benzoylamino)-3-{5-[2-
(trifluoromethoxy)phenyl]-2-furyl}prop-2- enoic acid; 155.
##STR192## (2Z)-2-(benzoylamino)-3-(4-phenylthien-
2-yl)prop-2-enoic acid; 156. ##STR193##
(2Z)-2-(benzoylamino)-3-(5-pyridin-2- ylthien-2-yl)prop-2-enoic
acid; 157. ##STR194## (2Z)-2-(benzoylamino)-3-(5-
phenylisoxazol-3-yl)prop-2-enoic acid; 158. ##STR195##
(2Z)-2-(benzoylamino)-3-[5-(2- fluorophenyl)thien-2-yl]prop-2-enoic
acid; 159. ##STR196## (2Z)-2-(benzoylamino)-3-[5-(2,5-
difluorophenyl)thien-2-yl]prop-2-enoic acid; 160. ##STR197##
(2Z)-2-(benzoylamino)-3-{5-[2-
(hydroxymethyl)phenyl]thien-2-yl}prop-2- enoic acid; 161.
##STR198## (2Z)-2-(benzoylamino)-3-[5-(2-
methoxyphenyl)thien-2-yl]prop-2-enoic acid; 162. ##STR199##
(2Z)-2-(benzoylamino)-3-(3-methyl-1- benzothien-2-yl)prop-2-enoic
acid; 163. ##STR200## (2Z)-2-[(2-methylbenzoyl)amino]-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 164. ##STR201##
(2Z)-2-[(4-nitrobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid;
165. ##STR202## (2Z)-2-(benzoylamino)-3-(5-phenyl-1,3-
thiazol-2-yl)prop-2-enoic acid; 166. ##STR203##
(2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)-1,3-thiazol-2-yl]prop-2- enoic acid; 167. ##STR204##
(2Z)-2-(benzoylamino)-3-[2-(2-
chlorophenyl)-1,3-thiazol-5-yl]prop-2- enoic acid; 168. ##STR205##
(2Z)-2-(benzoylamino)-3-[4-(2-
chlorophenyl)-1,3-thiazol-2-yl]prop-2- enoic acid; 169. ##STR206##
(2Z)-2-(benzoylamino)-3-[4-phenyl-5-
(trifluoromethyl)thien-2-yl]prop-2-enoic acid; 170. ##STR207##
(2Z)-2-(beta-alanylamino)-3-(5-phenyl-2- furyl)prop-2-enoic acid
trifluoroacetate; 171. ##STR208##
(2Z)-2-(benzoylamino)-3-{5-[2-chloro-5-
(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 172.
##STR209## (2Z)-2-(benzoylamino)-3-{5-[2,6-dichloro-
4-(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 173.
##STR210## (2Z)-2-(benzoylamino)-3-(2'-chloro-1,1'-
biphenyl-3-yl)prop-2-enoic acid; 174. ##STR211##
(2Z)-2-(benzoylamino)-3-[2-(2-
chlorophenyl)-1,3-thiazol-4-yl]prop-2- enoic acid; 175. ##STR212##
(2Z)-2-(benzoylamino)-3-[4- (trifluoromethyl)phenyl]prop-2-enoic
acid; 176. ##STR213## methyl (2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoate; 177. ##STR214##
(2Z)-2-[(2-hydroxybenzoyl)amino]-3-[5-(2-
methylphenyl)thien-2-yl]prop-2-enoic acid; 178. ##STR215##
(2Z)-3-[5-(2,3-difluorophenyl)thien-2-yl]-2-
[(2-hydroxybenzoyl)amino]prop-2-enoic acid; 179. ##STR216##
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-
fluoro-1,1-biphenyl-3-yl)prop-2-enoic acid; 180. ##STR217##
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-
methoxy-1,1'-biphenyl-3-yl)prop-2-enoic acid; 181. ##STR218##
(2Z)-2-(benzoylamino)-3-(2'-chloro-5,6-
dimethoxy-1,1'-biphenyl-3-yl)prop-2-enoic acid; 182. ##STR219##
(2Z)-2-(benzoylamino)-3-(2,3-difluoro-
1,1'-biphenyl-3-yl)prop-2-enoic acid; 183. ##STR220##
(2Z)-2-(benzoylamino)-3-(2-chloro-4-
fluoro-1,1'-biphenyl-3-yl)prop-2-enoic acid; 184. ##STR221##
(2Z)-2-(benzoylamino)-3-(2-chloro-4-
methoxy-1,1'-biphenyl-3-yl)prop-2-enoic acid; 185. ##STR222##
(2Z)-3-(2-chloro-6-fluoro-1,1'-biphenyl-3-
yl)-2-[(2-hydroxybenzoyl)amino]prop-2- enoic acid; 186. ##STR223##
(2Z)-2-(benzoylamino)-3-[4-chloro-3-
(trifluoromethyl)phenyl]prop-2-enoic acid; 187. ##STR224##
(2Z)-2-(benzoylamino)-3-(3- phenoxyphenyl)prop-2-enoic acid; 188.
##STR225## (2Z)-2-(benzoylamino)-3-(4-methyl-2-
phenyl-1,3-thiazol-5-yl)prop-2-enoic acid; 189. ##STR226##
(2Z)-2-(benzoylamino)-3-[6-(2-
chlorophenyl)pyridin-2-yl]prop-2-enoic acid; 190. ##STR227##
(2Z)-2-(benzoylamino)-3-[2-(2-
chlorophenyl)-1H-imidazol-5-yl]prop-2- enoic acid; 191. ##STR228##
(2Z)-2-(benzoylamino)-3-(2'-chloro-6-
hydroxy-1,1'-biphenyl-3-yl)prop-2-enoic acid; 192. ##STR229##
(2Z)-2-(benzoylamino)-3-(1-methyl-1H- indol-2-yl)prop-2-enoic acid;
193. ##STR230## (2Z)-2-(benzoylamino)-3-(3-pyridin-2-
ylphenyl)prop-2-enoic acid; 194. ##STR231##
(2Z)-2-(benzoylamino)-3-(3-pyridin-3- ylphenyl)prop-2-enoic acid;
195. ##STR232## (2Z)-2-(benzoylamino)-3-(3-pyridin-4-
ylphenyl)prop-2-enoic acid; 196. ##STR233##
(2Z)-2-(benzoylamino)-3-(4- phenoxyphenyl)prop-2-enoic acid; 197.
##STR234## 3-{5-[(Z)-2-(benzoylamino)-2-
carboxyethenyl]-2-furyl}thiophene-2- carboxylic acid; 198.
##STR235## (2Z)-2-(benzoylamino)-3-{5-[1-methyl-3-
(trifluoromethyl)-1H-pyrazol-5-yl]thien-2- yl}prop-2-enoic acid;
199. ##STR236## (2Z)-2-(benzoylamino)-3-{5-[1-methyl-5-
(trifluoromethyl)-1H-pyrazol-3-yl]thien-2- yl}prop-2-enoic acid;
200. ##STR237## (2Z)-2-(benzoylamino)-3-(2,4-dichloro-
1,1'-biphenyl-3-yl)prop-2-enoic acid; 201. ##STR238##
(2Z)-2-(benzoylamino)-3-(2',5'-dichloro-
1,1'-biphenyl-3-yl)prop-2-enoic acid; 202. ##STR239##
(2Z)-2-(benzoylamino)-3-(2',4-dichloro-
1,1'-biphenyl-3-yl)prop-2-enoic acid; 203. ##STR240##
(2Z)-2-(benzoylamino)-3-[5-(2,5-
dichlorophenyl)-2-furyl]prop-2-enoic acid; 204. ##STR241##
(2Z)-2-(benzoylamino)-3-{5-[2-chloro-4-
(trifluoromethyl)phenyl]-2-furyl}prop-2- enoic acid; 205.
##STR242## (2Z)-2-(benzoylamino)-3-[5-(2-
chlorophenyl)pyridin-3-yl]prop-2-enoic acid; 206. ##STR243##
(2Z)-2-(benzoylamino)-3-(2-methyl-1,1'- biphenyl-3-yl)prop-2-enoic
acid; 207. ##STR244## 2-[(Z)-2-(benzoylamino)-2-
carboxyethenyl]-5-(4-chlorophenyl)-3- furoic acid; 208. ##STR245##
(2Z)-2-(benzoylamino)-3-[4-(2- chlorophenoxy)phenyl]prop-2-enoic
acid; 209. ##STR246## (2Z)-2-(benzoylamino)-3-[2'-
(trifluoromethyl)-1,1'-biphenyl-3-yl]prop-2- enoic acid; 210.
##STR247## N-[(Z)-2-[5-(2-chlorophenyl)thien-2-yl]-1- (piperazin-1-
ylcarbonyl)ethenyl]benzamide; 211. ##STR248## methyl
N-{(2Z)-2-(benzoylamino)-3-[5-(2- chlorophenyl)thien-2-yl]prop-2-
enoyl}glycinate; 212. ##STR249## (2Z)-2-(benzoylamino)-3-[4-
(phenylthio)phenyl]prop-2-enoic acid; 213. ##STR250##
(2Z)-2-(benzoylamino)-3-[4- (phenylsulfonyl)phenyl]prop-2-enoic
acid; 214. ##STR251## (2Z)-2-(benzoylamino)-3-(2-hydroxy-1,1'-
biphenyl-3-yl)prop-2-enoic acid; 215. ##STR252##
(2Z)-2-(benzoylamino)-3-[4-phenoxy-2-
(trifluoromethyl)phenyl]prop-2-enoic acid; 216. ##STR253##
(2Z)-2-(benzoylamino)-3-[4-phenoxy-3-
(trifluoromethyl)phenyl]prop-2-enoic acid; 217. ##STR254##
(2Z)-2-(benzoylamino)-3-(3-cyano-4- phenoxyphenyl)prop-2-enoic
acid; 218. ##STR255## 3-{5-[(Z)-2-(benzoylamino)-2-
carboxyethenyl]-2-furyl}-4- methylthiophene-2-carboxylic acid; 219.
##STR256## (2Z)-2-(benzoylamino)-3-[4-
(benzyloxy)phenyl]prop-2-enoic acid; 220. ##STR257## 221.
##STR258## (2Z)-2-(benzoylamino)-3-(2-morpholin-4-
ylphenyl)prop-2-enoic acid; 222. ##STR259##
3'-[(Z)-2-(benzoylamino)-2-
carboxyethenyl]-1,1'-biphenyl-2-carboxylic acid; 223. ##STR260##
(2Z)-2-(benzoylamino)-3-(2'-cyano-1,1'- biphenyl-3-yl)prop-2-enoic
acid; 224. ##STR261## (2Z)-3-[4-(1H-benzimidazol-1-yl)phenyl]-
2-(benzoylamino)prop-2-enoic acid; 225. ##STR262##
(2Z)-2-(benzoylamino)-3-[4-(2- fluorophenoxy)phenyl]prop-2-enoic
acid; 226. ##STR263## (2Z)-2-(Benzoylamino)-3-[4-(2-
bromophenoxy)phenyl]-2-propenoic acid (uninverted GAS name
09/27/02) or V00074604 or V00080919 or (2Z)-2-
(benzoylamino)-3-[4-(2- bromophenoxy)phenyl]prop-2-enoic acid; 227.
##STR264## (2Z)-2-(benzoylamino)-3-[4-(2-
chlorophenoxy)-3-methylphenyl]prop-2- enoic acid; 228. ##STR265##
(2Z)-2-(benzoylamino)-3-[4-(2- chlorophenoxy)-3-nitrophenyl]prop-2-
enoic acid; 229. ##STR266## (2Z)-2-(benzoylamino)-3-(3-pyrimidin-5-
ylphenyl)prop-2-enoic acid; 230. ##STR267##
(2Z)-2-(benzoylamino)-3-[4-(2- cyanophenoxy)phenyl]prop-2-enoic
acid; 231. ##STR268## (2Z)-2-(benzoylamino)-3-[4-(2-
chlorophenoxy)-2- (trifluoromethyl)phenyl]prop-2-enoic acid; 232.
##STR269## (2Z)-2-(benzoylamino)-3-{4-[(2-
chlorophenyl)thio]phenyl}prop-2-enoic acid; 233. ##STR270##
2-{5-[(Z)-2-(benzoylamino)-2- carboxyethenyl]thien-2-yl}benzoic
acid; 234. ##STR271## (2Z)-2-(benzoylamino)-3-[5-(2-
cyanophenyl)thien-2-yl]prop-2-enoic acid; 235. ##STR272##
(2Z)-2-(benzoylamino)-3-(3'-formyl-1,1'- biphenyl-3-yl)prop-2-enoic
acid; 236. ##STR273## (2Z)-2-(benzoylamino)-3-[4-(3-
chlorophenoxy)phenyl]prop-2-enoic acid; 237. ##STR274##
(2Z)-2-(benzoylamino)-3-[3-chloro-4-(2-
chlorophenoxy)phenyl]prop-2-enoic acid; 238. ##STR275##
(2Z)-2-(benzoylamino)-3-{4-[(2-
chlorobenzyl)oxy]phenyl}prop-2-enoic acid; 239. ##STR276##
(2Z)-2-(benzoylamino)-3-{5-[(2-
chlorophenyl)thio]-2-furyl}prop-2-enoic acid; 240. ##STR277##
(2Z)-2-(benzoylamino)-3-{5-[(2-
chlorophenyl)thio]thien-2-yl)prop-2-enoic acid; 241. ##STR278##
(2Z)-2-(benzoylamino)-3-[4-(2- phenylethoxy)phenyl]prop-2-enoic
acid; 242. ##STR279## (2Z)-2-(benzoylamino)-3-[4-(2,3-
dichlorophenoxy)phenyl]prop-2-enoic acid; 243. ##STR280##
(2Z)-2-(benzoylamino)-3-{4-[(2-
bromophenyl)thio]phenyl}prop-2-enoic acid; 244. ##STR281##
(2Z)-2-(benzoylamino)-3-[4-(2- methoxyphenoxy)phenyl]prop-2-enoic
acid; 245. ##STR282## (2Z)-2-(benzoylamino)-3-[4-(2-
ethylphenoxy)phenyl]prop-2-enoic acid; 246. ##STR283##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-
fluorophenoxy)phenyl]prop-2-enoic acid; 247. ##STR284##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-5-
fluorophenoxy)phenyl]prop-2-enoic acid; 248. ##STR285##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-
chlorophenoxy)phenyl]prop-2-enoic acid; 249. ##STR286##
(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)-3-fluorophenyl]prop-2-
enoic acid; 250. ##STR287## (2Z)-2-(benzoylamino)-3-{5-[(2-
bromophenyl)thio]-2-furyl}prop-2-enoic acid; 251. ##STR288##
(2Z)-3-(2-amino-1,1'-biphenyl-3-yl)-2- (benzoylamino)prop-2-enoic
acid; 252. ##STR289## (2Z)-2-(benzoylamino)-3-(2-hydroxy-1,1'-
biphenyl-3-yl)prop-2-enoic acid; 253. ##STR290##
(2Z)-2-(benzoylamino)-3-(2'-nitro-1,1'- biphenyl-3-yl)prop-2-enoic
acid; 254. ##STR291## (2Z)-2-(benzoylamino)-3-[5-(2-
nitrophenyl)thien-2-yl]prop-2-enoic acid; 255. ##STR292##
(2Z)-3-[5-(2-aminophenyl)thien-2-yl]-2- (benzoylamino)prop-2-enoic
acid; 256. ##STR293## (2Z)-2-(benzoylamino)-3-{4-[(2-
chlorophenyl)amlno]phenyl}prop-2-enoic acid; 257. ##STR294##
(2Z)-2-(benzoylamino)-3-[4-(2- methylphenoxy)phenyl]prop-2-enoic
acid; 258. ##STR295## (2Z)-2-(benzoylamino)-3-[4-(2-
isopropoxyphenoxy)phenyl]prop-2-enoic acid; 259. ##STR296##
(2Z)-2-(benzoylamino)-3-[4-(2- iodophenoxy)phenyl]prop-2-enoic
acid; 260. ##STR297## (2Z)-2-(benzoylamino)-3-{5-[(2-
bromophenyl)thio]thien-2-yl}prop-2-enoic acid; 261. ##STR298##
(2Z)-2-(benzoylamino)-3-{2-[(2-
bromophenyl)thio]-1,3-thiazol-4-yl}prop-2- enoic acid; 262.
##STR299## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-{[4-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 263. ##STR300##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(3,4,5-trimethoxybenzoyl)amino]prop-2- enoic acid; 264. ##STR301##
(2Z)-2-(benzoylamino)-3-{4-[2-chloro-3-
(trifluoromethyl)phenoxy]phenyl}prop-2- enoic acid; 265. ##STR302##
(2Z)-2-(benzoylamino)-3-{4-[2-
(methylthio)phenoxy]phenyl}prop-2-enoic acid; 266. ##STR303##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-4-
cyanophenoxy)phenyl]prop-2-enoic acid; 267. ##STR304##
(2Z)-2-(benzoylamino)-3-[4-(2- bromobenzoyl)phenyl]prop-2-enoic
acid; 268. ##STR305## (2Z)-2-(benzoylamino)-3-{4-[(2-
chlorophenyl)(methyl)amino]phenyl}prop- 2-enoic acid; 269.
##STR306## (2Z)-2-(benzoylamino)-3-(4-(2-bromo-4-
methylphenoxy)phenyl]prop-2-enoic acid; 270. ##STR307##
(2Z)-2-(benzoylamino)-3-[4-(2-
cyclopentylphenoxy)phenyl]prop-2-enoic acid; 271. ##STR308##
(2Z)-2-(benzoylamino)-3-{4-[2-
(trifluoromethoxy)phenoxy]phenyl}prop-2- enoic acid; 272.
##STR309## (2Z)-2-(benzoylamino)-3-[4-(1,1'-biphenyl-
2-yloxy)phenyl]prop-2-enoic acid; 273. ##STR310##
(2Z)-2-(benzoylamino)-3-[4-(2,3-
difluorophenoxy)phenyl]prop-2-enoic acid; 274. ##STR311##
(2Z)-2-(benzoylamino)-3-[4-(2- isopropylphenoxy)phenyl]prop-2-enoic
acid; 275. ##STR312## (2Z)-2-(benzoylamino)-3-[4-(2-chloro-4-
methoxyphenoxy)phenyl]prop-2-enoic acid; 276. ##STR313##
(2Z)-2-(benzoylamino)-3-[4-(2- nitrophenoxy)phenyl]prop-2-enoic
acid; 277. ##STR314## (2Z)-2-(benzoylamino)-3-{4-[(1-bromo-2-
naphthyl)oxy]phenyl}prop-2-enoic acid; 278. ##STR315##
(2Z)-2-(benzoylamino)-3-(4-{[4-nitro-2-
(trifluoromethyl)cyclohexa-1,5-dien-1- yl]oxy}phenyl)prop-2-enoic
acid; 279. ##STR316## (2Z)-3-(4-{[4-amino-2-
(trifluoromethyl)cyclohexa-1,5-dien-1-
yl]oxy}phenyl)-2-(benzoylamino)prop-2- enoic acid; 280. ##STR317##
(2Z)-2-(benzoylamino)-3-{4-[2-
(trifluoromethyl)phenoxy]phenyl}prop-2- enoic acid; 281. ##STR318##
(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)-3-nitrophenyl]prop-2-
enoic acid; 282. ##STR319## (2Z)-2-(benzoylamino)-3-[4-
(phenoxymethyl)phenyl]prop-2-enoic acid; 283. ##STR320##
(2Z)-2-(benzoylamino)-3-[4-(pyridin-2-
ylmethoxy)phenyl]prop-2-enoic acid; 284. ##STR321##
(2Z)-2-(benzoylamino)-3-{4-[(2-
fluorobenzyl)oxy]phenyl}prop-2-enoic acid; 285. ##STR322##
(2Z)-2-(benzoylamino)-3-(4-{[3-
(trifiuoromethyl)benzyl]oxy}phenyl)prop-2- enoic acid; 286.
##STR323## (2Z)-3-[3-amino-4-(2- bromophenoxy)phenyl]-2-
(benzoylamino)prop-2-enoic acid; 287. ##STR324## methyl
(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)phenyl]prop-2-enoate;
288. ##STR325## (2Z)-2-(benzoylamino)-3-{4-[(4-
cyanobenzyl)oxy]phenyl}prop-2-enoic acid; 289. ##STR326##
(2Z)-2-(benzoylamino)-3-[4-(pyridin-3-
ylmethoxy)phenyl]prop-2-enoic acid; 290. ##STR327##
(2Z)-2-(benzoylamino)-3-[4-(pyridin-4-
ylmethoxy)phenyl]prop-2-enoic acid; 291. ##STR328##
(2Z)-2-(benzoylamino)-3-(4-{[4-
(trifluoromethyl)benzyl]oxy}phenyl)prop-2- enoic acid; 292.
##STR329## (2Z)-2-(benzoylamino)-3-{4-[(4-
fluorobenzyl)oxy]phenyl}prop-2-enoic acid; 293. ##STR330##
(2Z)-2-(benzoylamino)-3-{4-[(3- nitrobenzyl)oxy]phenyl}prop-2-enoic
acid; 294. ##STR331## (2Z)-2-(benzoylamino)-3-{4-[(4-
methylbenzyl)oxy]phenyl}prop-2-enoic acid; 295. ##STR332##
(2Z)-2-(benzoylamino)-3-{4-[(4-
chlorobenzyl)oxy]phenyl}prop-2-enoic acid; 296. ##STR333##
N-[(1Z)-1-(aminocarbonyl)-2-[4-(2-
bromophenoxy)phenyl]ethenyl]benzamide 297. ##STR334##
(2Z)-2-(benzoylamino)-3-[3- (benzyloxy)phenyl]prop-2-enoic acid;
298. ##STR335## (2Z)-2-[benzoyl(methyl)amino]-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 299. ##STR336##
(2Z)-2-(benzoylamino)-3-[3-(4- chlorophenoxy)phenyl]prop-2-enoic
acid; 300. ##STR337## (2Z)-2-(benzoylamino)-3-[3-(4-
methylphenoxy)phenyl]prop-2-enoic acid; 301. ##STR338##
(2Z)-2-(benzoylamino)-3-[3-(4- methoxyphenoxy)phenyl]prop-2-enoic
acid; 302. ##STR339## (2Z)-2-(benzoylamino)-3-{3-[(2-
chlorobenzyl)oxy]phenyl}prop-2-enoic acid; 303. ##STR340##
(2Z)-2-(benzoylamino)-3-{4-((3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 304. ##STR341##
(2Z)-2-(benzoylamino)-3-{4-[(3-
chlorobenzyl)oxy]phenyl}prop-2-enoic acid; 305. ##STR342##
(2Z)-2-(benzoylamino)-3-(4-{[3-
(trifluoromethoxy)benzyl]oxy}phenyl)prop- 2-enoic acid; 306.
##STR343## (2Z)-2-(benzoylamino)-3-[3-(2-
chlorophenoxy)phenyl]prop-2-enoic acid; 307. ##STR344##
(2Z)-2-(benzoylamino)-3-[3-(2- bromophenoxy)phenyl]prop-2-enoic
acid; 308. ##STR345## (2Z)-2-(benzoylamino)-3-[3-(2-chloro-4-
nitrophenoxy)phenyl]prop-2-enoic acid; 309. ##STR346## 2-{[(2-
phenoxyphenyl)amino]carbonyl}benzoic acid; 310. ##STR347##
(2Z)-2-(benzoylamino)-3-{4-[(3-
methylbenzyl)oxy]phenyl}prop-2-enoic acid; 311. ##STR348##
(2Z)-2-(benzoylamino)-3-[4-(2-tert-
butylphenoxy)phenyl]prop-2-enoic acid; 312. ##STR349##
(2Z)-2-(benzoylamino)-3-{4-[(3-
fluorobenzyl)oxy]phenyl}prop-2-enoic acid; 313. ##STR350##
(2Z)-2-(benzoylamino)-3-{4-[(3- cyanobenzyl)oxy]phenyl}prop-2-enoic
acid; 314. ##STR351## (2Z)-2-(benzoylamino)-3-{3-[3-
(trifluoromethyl)phenoxy]phenyl}prop-2- enoic acid; 315. ##STR352##
(2Z)-2-(benzoylamino)-3-[3-(4-tert-
butylphenoxy)phenyl]prop-2-enoic acid; 316. ##STR353##
(2Z)-3-[4-(2-amino-6- chlorophenoxy)phenyl]-2-
(benzoylamino)prop-2-enoic acid; 317. ##STR354##
(2Z)-2-(benzoylamino)-3-[4-(2,6-
dichlorophenoxy)phenyl]prop-2-enoic acid; 318. ##STR355##
(2Z)-2-(benzoylamino)-3-[4-(2-chloro-6-
nitrophenoxy)phenyl]prop-2-enoic acid; 319. ##STR356##
(2Z)-2-(benzoylamino)-3-[4-(3- methoxyphenoxy)phenyl]prop-2-enoic
acid; 320. ##STR357## methyl (2Z)-3-[5-(2-aminophenyl)thien-2-
yl]-2-(benzoylamino)prop-2-enoate; 321. ##STR358##
N-[(E)-2-bromo-2-(2-methoxyphenyl)-1-
(piperidin-1-ylcarbonyl)ethenyl]-4- nitrobenzamide; 322. ##STR359##
3-({4-[(Z)-2-(benzoylamino)-2-
carboxyethenyl]phenoxy}methyl)benzoic acid; 323. ##STR360##
(2Z)-2-(benzoylamino)-3-{4-[(3,5-
dimethoxybenzyl)oxy]phenyl}prop-2-enoic acid; 324. ##STR361##
(2E)-2-(benzoylamino)-3-bromo-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 325. ##STR362##
(2Z)-2-(benzoylamino)-3-[4-(2-chloro-6-
fluorophenoxy)phenyl]prop-2-enoic acid; 326. ##STR363##
N-benzoyl-O-(2-bromophenyl)tyrosine; 327. ##STR364##
(2Z)-2-(benzoylamino)-3-[3-(2-chloro-6-
nitrophenoxy)phenyl]prop-2-enoic acid; 328. ##STR365##
(2Z)-3-[3-(2-amino-6- chlorophenoxy)phenyl]-2-
(benzoylamino)prop-2-enoic acid; 329. ##STR366##
(2Z)-2-(benzoylamino)-3-[5-(2- bromophenoxy)-2-nitrophenyl]prop-2-
enoic acid; 330. ##STR367##
(2Z)-3-{4-[(3-aminobenzyl)oxy]phenyl}-2- (benzoylamino)prop-2-enoic
acid; 331. ##STR368## (2Z)-2-{[(5-bromopyridin-3-
yl)carbonyl]amino}-3-[5-(2- chlorophenyl)thien-2-yl]prop-2-enoic
acid; 332. ##STR369## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(2,4-dichlorobenzoyl)amino]prop-2-enoic acid; 333. ##STR370##
(2Z)-2-({[3-(2,6-dichlorophenyl)-5-
methylisoxazol-4-yl]carbonyl}amino)-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 334. ##STR371##
(2Z)-2-[(2,4-difluorobenzoyl)amino]-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 335. ##STR372##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-6-
nitrophenoxy)phenyl]prop-2-enoic acid; 336. ##STR373##
(2Z)-3-[4-(2-amino-6- bromophenoxy)phenyl]-2-
(benzoylamino)prop-2-enoic acid; 337. ##STR374##
(2Z)-2-(benzoylamino)-3-[4-(2,6-
difluorophenoxy)phenyl]prop-2-enoic acid; 338. ##STR375##
(2Z)-2-(benzoylamino)-3-[4-(2-bromo-6-
fluorophenoxy)phenyl]prop-2-enoic acid; 339. ##STR376##
(2Z)-2-(benzoylamino)-3-[4-(2-fluoro-6-
methoxyphenoxy)phenyl]prop-2-enoic acid; 340. ##STR377## methyl
(2Z)-2-(benzoylamino)-3-[4-(2-
chloro-6-fluorophenoxy)phenyl]prop-2- enoate; 341. ##STR378##
N-{(Z)-1-(aminocarbonyl)-2-[4-(2-chloro-6-
fluorophenoxy)phenyl]ethenyl}benzamide; 342. ##STR379##
(2Z)-2-(benzoylamino)-3-{4-[(2,6-
dichlorophenyl)thio]phenyl)prop-2-enoic acid; 343. ##STR380##
(2Z)-3-[3-(2-aminophenoxy)phenyl]-2- (benzoylamino)prop-2-enoic
acid; 344. ##STR381## (2Z)-2-(benzoylamino)-3-[3-(2-
nitrophenoxy)phenyl]prop-2-enoic acid; 345. ##STR382##
(2Z)-2-(benzoylamino)-3-(2- naphthyl)prop-2-enoic acid; 346.
##STR383## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(pentafluorobenzoyl)amino]prop-2-enoic acid; 347. ##STR384##
(2Z)-2-{[(2,5-dichlorothien-3- yl)carbonyl]amino}-3-(5-phenyl-2-
furyl)prop-2-enoic acid; 348. ##STR385## (2Z)-2-{[3,5-
bis(trifluoromethyl)benzoyl]amino}-3-[5-
(2-chlorophenyl)thien-2-yl]prop-2-enoic acid; 349. ##STR386##
(2Z)-2-{[3,5- bis(trifluoromethyl)benzoyl]amino}-3-[4-
(2-bromophenoxy)phenyl]prop-2-enoic acid; 350. ##STR387##
(2Z)-2-[(5-nitro-2-furoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 351. ##STR388## (2Z)-2-[(2-chlorobenzoyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 352. ##STR389##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(5-
nitro-2-furoyl)amino]prop-2-enoic acid; 353. ##STR390##
(2Z)-2-[(3-bromobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 354. ##STR391## (2Z)-2-[(2,5-dimethyl-3-furoyl)amino]-3-
(5-phenyl-2-furyl)prop-2-enoic acid; 355. ##STR392##
(2Z)-3-{4-[(3-methoxybenzyl)oxy]phenyl}-
2-{[2-(trifluoromethyl)benzoyl]amino)prop- 2-enoic acid;
[0407] TABLE-US-00004 356. ##STR393##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-{[2-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 357. ##STR394##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(5-
nitro-2-furoyl)amino]prop-2-enoic acid; 358. ##STR395##
(2Z)-2-[(3-bromobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 359. ##STR396##
(2Z)-2-[(1-benzothien-2- ylcarbonyl)amino]-3-(5-phenyl-2-
furyl)prop-2-enoic acid; 360. ##STR397##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 361. ##STR398##
(2Z)-2-{[(6-chloropyridin-3- yl)carbonyl]amino}-3-(5-phenyl-2-
furyl)prop-2-enoic acid; 362. ##STR399##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(2,5-dimethyl-3-furoyl)amino]prop-2- enoic acid; 363. ##STR400##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2- {[(6-chtoropyridin-3-
yl)carbonyl]amino}prop-2-enoic acid; 364. ##STR401##
(2Z)-2-[(2,4-dichlorobenzoyl)aminol-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 365. ##STR402##
(2Z)-2-[(2-chlorobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 366. ##STR403## (2Z)-2-[(1-benzothien-2-
ylcarbonyl)amino]-3-[5-(2- chlorophenyi)thien-2-yl]prop-2-enoic
acid; 367. ##STR404## (2Z)-2-[(3-chlorobenzoyl)amino]-3-[5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 368. ##STR405##
(2Z)-2-[(2-chlorobenzoyl)amino]-3-(5-(2-
chlorophenyl)thien-2-yl]prop-2-enoic acid; 369. ##STR406##
(2Z)-2-[(2-bromobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 370. ##STR407## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(2,5-dichlorothien-3- yl)carbonyl]amino}prop-2-enoic acid; 371.
##STR408## (2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
{[(2,5-dichlorothien-3- yl)carbonyl]amino}prop-2-enoic acid; 372.
##STR409## (2Z)-2-[(2,6-difluorobenzoyl)amino]-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 373. ##STR410##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(4-
cyanobenzoyl)amino]prop-2-enoic acid; 374. ##STR411##
(2Z)-3-(5-phenyl-2-furyl)-2-{[2-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 375. ##STR412##
(2Z)-2-{[3,5- bis(trifluoromethyl)benzoyl]amino}-3-(5-
phenyl-2-furyl)prop-2-enoic acid; 376. ##STR413##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4-
cyanobenzoyl)amino]prop-2-enoic acid; 377. ##STR414##
(2Z)-2-[(3-chlorobenzoyl)amino]-3-(5- phenyl-2-furyl)prop-2-enoic
acid; 378. ##STR415## (2Z)-3-(5-(2-chlorophenyl)thien-2-yl]-2-[(3-
fluorobenzoyl)amino]prop-2-enoic acid; 379. ##STR416##
(2Z)-2-{[(5-bromopyridin-3- yl)carbonyl]amino}-3-(5-phenyl-2-
furyl)prop-2-enoic acid; 380. ##STR417## (2Z)-2-[(1-benzothien-2-
ylcarbonyl)amino]-3-[4-(2- bromophenoxy)phenyi]prop-2-enoic acid;
381. ##STR418## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2,6-dimethoxybenzoyl)amino]prop-2- enoic acid; 382. ##STR419##
(2Z)-2-{[(6-chloropyridin-3- yl)carbonyl]amino}-3-{4-[(3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 383. ##STR420##
(2Z)-2-{[(6-bromopyridin-3- yl)carbonyl]amino}-3-{4-[(3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 384. ##STR421##
(2Z)-2-[(1-benzothien-2- ylcarbonyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 385. ##STR422##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
[(2,6-difiuorobenzoyl)amino]prop-2-enoic acid; 386. ##STR423##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-
({[3-(2,6-dichlorophenyl)-5-
methylisoxazol-4-yl]carbonya}amino)prop- 2-enoic acid; 387.
##STR424## (2Z)-2-[(3-bromobenzoyl)amino]-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 388. ##STR425##
(2Z)-2-(benzoylamino)-3-[4-(2-chloro-6-
methylphenoxy)phenyl]prop-2-enoic acid; 389. ##STR426##
(2Z)-2-(benzoylamino)-3-[4-(2-chloro-5-
methoxyphenoxy)phenyl]prop-2-enoic acid; 390. ##STR427##
(2Z)-2-(benzoylamino)-3-[4-(2,3,6-
trifluorophenoxy)phenyl]prop-2-enoic acid; 391. ##STR428##
(2Z)-2-(benzoylamino)-3-[4-(6-chloro-2-
fluoro-3-methylphenoxy)phenyl]prop-2- enoic acid; 392. ##STR429##
(2Z)-2-(benzoylamino)-3-{4-[(3-
ethoxybenzyl)oxy]phenyl}prop-2-enoic acid; 393. ##STR430##
(2Z)-2-(benzoylamino)-3-{4-[(2-fluoro-5-
methoxybenzyl)oxy]phenyl}prop-2-enoic acid; 394. ##STR431##
(2Z)-2-(benzoylamino)-3-{4-[(3- bromobenzyl)oxy]phenyl}prop-2-enoic
acid; 395. ##STR432## (2Z)-2-(benzoylamino)-3-{4-[(2-cyano-
1,1'-biphenyl-4-yl)methoxy]phenyl}prop-2- enoic acid; 396.
##STR433## (2Z)-2-(benzoylamino)-3-{4-[(3,4-
difluorobenzyl)oxy]phenyl}prop-2-enoic acid; 397. ##STR434##
(2Z)-2-(benzoylamino)-3-[4-(2,5-
difluorophenoxy)phenyl]prop-2-enoic acid; 398. ##STR435##
(2Z)-2-(benzoylamino)-3-[4-(2-fluoro-5-
methylphenoxy)phenyl]prop-2-enoic acid; 399. ##STR436##
(2Z)-2-(benzoylamino)-3-[4-(2- bromophenoxy)phenyl]but-2-enoic
acid; 400. ##STR437## (2Z)-2-(benzoylamino)-3-(4-{[3-(1H-
pyrrol-1-yl)benzyl]oxy}phenyl)prop-2- enoic acid; 401. ##STR438##
(2Z)-2-(benzoylamino)-3-(4-{[4-(1,2,3-
thiadiazol-4-yl)benzyl]oxy}phenyl)prop-2- enoic acid; 402.
##STR439## (2Z)-2-(benzoylamino)-3-(4-{[3-
(difluoromethoxy)benzyl]oxy}phenyl)prop- 2-enoic acid; 403.
##STR440## (2Z)-3-[4-(1,3-benzodioxol-4-
ylmethoxy)phenyl]-2-(benzoylamino)prop- 2-enoic acid; 404.
##STR441## (2Z)-2-(benzoylamino)-3-(4-{[4-(1H-1,2,4-
triazol-1-yl)benzyl]oxy}phenyl)prop-2- enoic acid; 405. ##STR442##
N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1-
{[hydroxy(methyl)amino]carbonyl}ethenyl) benzamide; or V00086354
406. ##STR443## [({(2Z)-2-(benzoylamino)-3-[4-(2-
bromophenoxy)phenyl]prop-2- enoyl}amino)oxy]acetic acid; 407.
##STR444## N-[(Z)-2-[4-(2-bromophenoxy)phenyl]-1-
(hydrazinocarbonyl)ethenyl]benzamide; or V00086355 408. ##STR445##
N-((Z)-2-(4-(2-bromophenoxy)phenyl]-1-
{[(methylsulfonyl)amino]carbonyl}ethenyl) benzamide; or V00086363
409. ##STR446## N-((Z)-2-[4-(2-bromophenoxy)phenyl]-1-
{[(phenylsulfonyl)amino]carbonyl)ethenyl) benzamide; 410.
##STR447## (2Z)-2-(benzoylamino)-3-[4-(2-chloro-3,6-
difluorophenoxy)phenyllprop-2-enoic acid; 411. ##STR448##
(2Z)-2-(benzoylamino)-3-(4-{[3-
(methoxymethoxy)benzyl]oxylphenyl)prop- 2-enoic acid 412.
##STR449## N-{(Z)-1- {[(aminosulfonyl)amino]carbonyl}-2-[4-(2-
bromophenoxy)phenyl]ethenyl}benzamide; or V00086468 413. ##STR450##
N-{(Z)-1-{[(benzyloxy)amino]carbonyl}-2- [4-(2-
bromophenoxy)phenyl]ethenyl}benzamide; 414. ##STR451##
N-{(Z)-2-[4-(2-bromophenoxy)phenyl]-1-
[(methoxyamino)carbonyl]ethenyl}benzamide; 415. ##STR452##
(2Z)-2-(benzoylamino)-3-{4-[(3-
hydroxybenzyl)oxy]phenyl}prop-2-enoic acid; 416. ##STR453##
N-((Z)-1-(aminocarbonyl)-2-{4-[(3-
methoxybenzyl)oxy]phenyl)ethenyl) benzamide; 417. ##STR454##
(2Z)-2-[(tert-butoxycarbonyl)amino]-3-[4-
(2-chlorophenoxy)phenyl]prop-2-enoic acid; 418. ##STR455##
N-{(Z)-1- {[(aminosulfonyl)amino]carbonyl}-2-[4-(2-
iodophenoxy)phenyl]ethenyl}benzamide; 419. ##STR456##
N-((Z)-2-[4-(2-iodophenoxy)phenyl]-1-
{[(methylsulfonyl)amino]carbonyl)ethenyl) benzamide; 420.
##STR457## N-[(Z)-2-[4-(2-iodophenoxy)phenyl]-1- ({[(4-
nitrophenyl)sulfonyl]amino}carbonyl) ethenyl]benzamide; 421.
##STR458## N-[(Z)-2-[4-(2-iodophenoxy)phenyl]-1- ({[(3-
nitrophenyl)sulfonyl]amino}carbonyl) ethenyl]benzamide; 422.
##STR459## N-[(Z)-2-[4-(2-bromophenoxy)phenyl]-1- ({[(4-
chlorophenyl)sulfonyl]amino}carbonyl) ethenyl]benzamide; 423.
##STR460## 2-hydroxyethyl (2Z)-2-(benzoylamino)-3-
[4-(2-bromophenoxy)phenyl]prop-2- enoate; 424. ##STR461##
(2Z)-2-[(3-fluorobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 425. ##STR462##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-[(3-
fluorobenzoyl)amino]prop-2-enoic acid; 426. ##STR463##
(2Z)-2-[(3-fluorobenzoyl)amino]-3-[4-(2-
fluorophenoxy)phenyl]prop-2-enoic acid; 427. ##STR464##
(2Z)-3-[4-(2-chloro-6- fluorophenoxy)phenyl]-2-[(3-
fluorobenzoyl)amino]prop-2-enoic acid; 428. ##STR465##
(2Z)-3-[4-(2-chloro-6- methylphenoxy)phenyl]-2-[(3-
fluorobenzoyl)amino]prop-2-enoic acid; 429. ##STR466##
(2Z)-2-[(3-chlorobenzoyl)amino]-3-[4-(2-
chlorophenoxy)phenyl]prop-2-enoic acid; 430. ##STR467##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
chlorobenzoyl)aminolprop-2-enoic acid; 431. ##STR468##
(2Z)-2-[(3-chlorobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 432. ##STR469##
(2Z)-2-[(3-chlorobenzoyl)amino]-3-[4-(2-
chloro-6-fluorophenoxy)phenyl]prop-2- enoic acid; 433. ##STR470##
(2Z)-2-[(2-fluorobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 434. ##STR471##
(2Z)-3-[4-(2-chloro-6- fluorophenoxy)phenyl]-2-[(2-
fluorobenzoyl)amino]prop-2-enoic acid; 435. ##STR472##
(2Z)-3-[4-(2-chloro-6- methylphenoxy)phenyl]-2-[(2-
fluorobenzoyl)amino]prop-2-enoic acid; 436. ##STR473##
(2Z)-2-[(3-aminobenzoyl)amino]-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 437. ##STR474##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(cyclohexylcarbonyl)amino]prop-2-enoic acid;
438. ##STR475## (2Z)-2-[(cyclohexylcarbonyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 439. ##STR476##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
cyanobenzoyl)amino]prop-2-enoic acid; 440. ##STR477##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
methoxybenzoyl)amino]prop-2-enoic acid; 441. ##STR478##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
nitrobenzoyl)amino]prop-2-enoic acid; 442. ##STR479##
(2Z)-2-(benzoylamino)-3-[4-(2-cyano-6-
fluorophenoxy)phenyl]prop-2-enoic acid; 443. ##STR480##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-
[(thien-2-ylcarbonyl)amino]acrylic acid; 444. ##STR481##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-
[(thien-2-ylacetyl)amino]acrylic acid; 445. ##STR482##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2- [(phenylacetyl)amino]acrylic
acid; 446. ##STR483## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-
[(phenoxyacetyl)amino]acrylic acid; 447. ##STR484##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-
{[(2E)-3-phenylprop-2-enoyl]amino}prop- 2-enoic acid; 448.
##STR485## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-
(lactoylamino)prop-2-enoic acid; 449. ##STR486##
(2Z)-2-[(4-carboxybutanoyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 450. ##STR487##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(thien-2-ylcarbonyl)amino]prop-2-enoic acid; 451. ##STR488##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(3-
methylbenzoyl)amino]prop-2-enoic acid; 452. ##STR489##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(4-
nitrobenzoyl)amino]prop-2-enoic acid; 453. ##STR490##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(4-
methylbenzoyl)amino]prop-2-enoic acid; 454. ##STR491##
(2Z)-2-{[(1-acetylpiperidin-4- yl)carbonyl]amino}-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 455. ##STR492##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(1- methyl-1H-pyrrol-2-
yl)carbonyl]amino}prop-2-enoic acid; 456. ##STR493##
(2Z)-2-[(1,3-benzodioxol-5- ylcarbonyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 457. ##STR494##
(2Z)-2-[(cyclopropylcarbonyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 458. ##STR495##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(3-
phenylpropanoyl)amino]prop-2-enoic acid; 459. ##STR496##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-iodophenoxy)phenyl]prop-2-enoic acid; 460. ##STR497## sodium
(2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]acrylate; 461. ##STR498##
(2Z)-2-(glycoloylamino)-3-[4-(2- iodophenoxy)phenyl]prop-2-enoic
acid; 462. ##STR499## (2Z)-2-[(2-hydroxy-2-
methylpropanoyl)amino]-3-[4-(2- iodophenoxy)phenyl]prop-2-enoic
acid; 463. ##STR500## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(2-
phenylbutanoyl)amino]prop-2-enoic acid; 464. ##STR501##
(2Z)-2-[(1-adamantylcarbonyl)amino]-3-
[4-(2-iodophenoxy)phenyl]prop-2-enoic acid; 465. ##STR502##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2- ({[(1S,2S)-2-
phenylcyclopropyl]carbonyl}amino)prop-2- enoic acid; 466.
##STR503## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[hydroxy(phenyl)acetyl]amino}prop-2- enoic acid; 467. ##STR504##
(1S,3R)-3-[({(Z)-1-carboxy-2-[4-(2-
iodophenoxy)phenyl]ethenyl}amino) carbonyl]-2-ethyl-3-hydroxy-1,2-
dimethylcyclopentanecarboxylic acid; 468. ##STR505##
(2Z)-2-{[(benzyloxy)acetyl]amino}-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 469. ##STR506##
(2Z)-2-[(1-benzothien-2- ylcarbonyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 470. ##STR507##
(2Z)-2-[(4-cyanobenzoyl)amino]-3-(4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 471. ##STR508##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(2-
nitrobenzoyl)amino]prop-2-enoic acid; 472. ##STR509##
(2Z)-2-[(1,1'-biphenyl-4- ylcarbonyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 473. ##STR510##
(2Z)-2-[(4-fluorobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 474. ##STR511##
(2Z)-2-[(4-chlorobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 475. ##STR512##
(2Z)-2-[(4-bromobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 476. ##STR513##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-[(4-
methoxybenzoyl)amino]prop-2-enoic acid; 477. ##STR514##
(2Z)-2-(2-furoylamino)-3-[4-(2- iodophenoxy)phenyl]prop-2-enoic
acid; 478. ##STR515## (2Z)-2-[(4-tert-butylbenzoyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 479. ##STR516##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-(1- naphthoylamino)prop-2-enoic
acid; 480. ##STR517## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-(2-
naphthoylamino)prop-2-enoic acid; 481. ##STR518##
NH(2Z)-2-[(3-carboxypropanoyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 482. ##STR519##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-
[(thien-2-ylcarbonyl)amino]prop-2-enoic acid; 483. ##STR520##
(2Z)-3-[4-(2-fluorophenoxy)phenyl]-2-
[(thien-2-ylcarbonyl)amino]prop-2-enoic acid; 484. ##STR521##
(2Z)-2-[(1-adamantylcarbonyl)amino]-3-
[4-(2-bromophenoxy)phenyl]prop-2-enoic acid; 485. ##STR522##
(2Z)-2-[(4-iodobenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 486. ##STR523##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4-
methylbenzoyl)amino]prop-2-enoic acid; 487. ##STR524##
(2Z)-2-[(4-ethylbenzoyl)amino]-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 488. ##STR525##
(2Z)-2-[(3-fluoro-4-methylbenzoyl)amino]-
3-[4-(2-iodophenoxy)phenyl]prop-2-enoic acid; 489. ##STR526##
(2Z)-2-[(5-carboxypentanoyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 490. ##STR527##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2- {[(3,4.5-trichlorothien-2-
yl)carbonyl]amino}prop-2-enoic acid; 491. ##STR528##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4-
chlorobenzoyl)amino]prop-2-enoic acid; 492. ##STR529##
(2Z)-2-((4-bromobenzoyl)amino]-3-[4-(2-
bromophenoxy)phenyl]prop-2-enoic acid; 493. ##STR530##
(2Z)-2-(benzoylamino)-3-[3-fluoro-4-(2-
fluorophenoxy)phenyl]prop-2-enoic acid; 494. ##STR531##
(2Z)-2-[(3-fluorobenzoyl)amino]-3-[3-
fluoro-4-(2-fluorophenoxy)phenyl]prop-2- enoic acid; 495.
##STR532## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 496. ##STR533## sodium
(2Z)-3-[4-(2- bromophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylate; 497. ##STR534##
(2Z)-2-{[4-(dimethylamino)benzoyl]amino}-3-[4-(2-
iodophenoxy)phenyl]prop-2-enoic acid; 498. ##STR535##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(1-
methylcyclohexyl)carbonyljamino}prop-2- enoic acid; 499. ##STR536##
(2Z)-2-[(cyclopentylcarbonyl)amino]-3-[4-
(2-iodophenoxy)phenyl]prop-2-enoic acid; 500. ##STR537##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- (hexanoylamino)prop-2-enoic
acid; 501. ##STR538## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(3,3-dimethylbutanoyl)amino]prop-2- enoic acid; 502. ##STR539##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- (butyrylamino)prop-2-enoic
acid; 503. ##STR540## (2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]prop-2-enoic acid; 504. ##STR541##
(2Z)-2-[(3,3-dimethylbutanoyl)amino]-3-
[4-(2-iodophenoxy)phenyl]prop-2-enoic acid; 505. ##STR542##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(3,4-dichlorobenzoyl)amino]prop-2-enoic acid; 506. ##STR543##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
methylbutanoyl)amino]prop-2-enoic acid; 507. ##STR544##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
hydroxy-2-methylbenzoyl)amino]prop-2- enoic acid; 508. ##STR545##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[4-
(trifluoromethyl)benzoyl]amino}prop-2- enoic acid; 509. ##STR546##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(3-
methylthien-2-yl)carbonyl]amino)prop-2- enoic acid; 510. ##STR547##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(3,4-difluorobenzoyl)amino]prop-2-enoic acid; 511. ##STR548##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
methylpentanoyl)amino]prop-2-enoic acid; 512. ##STR549##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- (pentanoylamino)prop-2-enoic
acid; 513. ##STR550## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
cyclohexylpropanoyl)amino]prop-2-enoic acid; 514. ##STR551##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-[(3-
cyclohexylpropanoyl)amino]prop-2-enoic acid; 515. ##STR552##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(cyclopentylacetyl)amino]prop-2-enoic acid; 516. ##STR553##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-((2-
ethylhexanoyl)amino]prop-2-enoic acid; 517. ##STR554##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- (pent-4-enoylam
ino)prop-2-enoic acid; 518. ##STR555##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
((3,5,5-trimethylhexanoyl)amino]prop-2- enoic acid; 519. ##STR556##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
{4-((3-methoxybenzyl)oxy]phenyl}prop-2- enoic acid; 520. ##STR557##
sodium (2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl}acrylate; 521. ##STR558## V00116684
522. ##STR559## V00116682 523. ##STR560## V00116736 or
(2Z)-3-[4-(2- bromophenoxy)phenyl]-2-{[(4-
chlorophenyl)acetyl]amino}acrylic acid; or V00116736 524.
##STR561## V00116637 525. ##STR562## V00116735 526. ##STR563##
V00116612 527. ##STR564## V00116739 528. ##STR565## V00116636 529.
##STR566## V00116660 or (2Z)-3-[4-(2- bromophenoxy)phenyl]-2-{[(4-
methylcyclohexyl)acetyl]amino}acrylic acid; 530. ##STR567##
V00116620 531. ##STR568## V00116614 532. ##STR569##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(1-
naphthylacetyl)amino]acrylic acid; or V00116661 533. ##STR570##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4-
cyclohexylbutanoyl)amino]acrylic acid; or V00116623 534. ##STR571##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(cycloheptylcarbonyl)amino]acrylic acid; or V00116630 535.
##STR572## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[4-
(trifluoromethyl)phenyl]acetyllamino)acrylic acid; or V00116641
536. ##STR573## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(5-methylthien-2- yl)carbonyl]amino)acrylic acid; 537. ##STR574##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4- butylbenzoyl)amino]acrylic
acid; or V00116733 538. ##STR575##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
methylpentanoyl)amino]acrylic acid; or V00116693 539. ##STR576##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(4-
ethoxybenzoyl)amino]acrylic acid; or V00116738 540. ##STR577##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- {[(4-tert-
butylcyclohexyl)carbonyl]amino}acrylic acid; or V00116692 541.
##STR578## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2- {[(4-
methylcyclohexyl)carbonyl]amino}acrylic acid; or V00116679 542.
##STR579## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(1-methyl-1H-indol-3- yl)acetyl]amino)acrylic acid; or V00116691
543. ##STR580## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
propylpentanoyl)amino]acrylic acid; or V00116624 544. ##STR581##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-isopropylphenyl)acetyl]amino}acrylic acid; or V00116663 545.
##STR582## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({3-
[3-(trifluoromethyl)phenyl]propanoyl}amino)acrylic acid; or
V00116646 546. ##STR583## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3- methylcyclohexyl)carbonyl]amino}acrylic acid; or V00116694
547. ##STR584## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2- ({[1-(4-
chlorophenyl)cyclopentyl]carbonyl}amino) acrylic acid; 548.
##STR585## (2Z)-3-[4-(2-bromophenoxy)-3- fluorophenyl]-2-[(3-
fluorobenzoyl)amino]acrylic acid; 549. ##STR586##
(2Z)-3-[4-(2-chloro-6- fluorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 550. ##STR587##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(5-
thien-2-ylpentanoyl)amino]acrylic acid; or V00116671 551.
##STR588## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[2-
(trifluoromethyl)phenyl]acetyllamino)acrylic acid; or V00116644
552. ##STR589## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2- {[(2,3,6-
trichlorophenyl)acetyl]amino}acrylic acid; or V00116621 553.
##STR590## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[(4-
propylcyclohexyl)carbonyl]amino}acrylic acid; or V001166711 554.
##STR591## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2- [(2,3-dihydro-1
H-inden-2- ylacetyl)amino]acrylic acid; or V00116705 555.
##STR592## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[1-(4-
chlorophenyl)cyclobutyl]carbonyl}amino) acrylic acid; or V00116653
556. ##STR593## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2,2-dimethylpent-4-enoyl)amino]acrylic acid; or V00116667 557.
##STR594## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3- fluoro-5-
(trifluoromethyl)benzoyl]amino}acrylic acid; or V00116734 558.
##STR595## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(2,3-difluorophenyl)acetyl]amino)acrylic acid; or V00116657 559.
##STR596## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(1-methyl-1H-indol-2- yl)carbonyl]amino}acrylic acid; or
V00116645 560. ##STR597## (2Z)-2-{((4-chlorophenyl)acetyl]amino}-3-
[4-(2-iodophenoxy)phenyl]acrylic acid; 561. ##STR598## V00116676 or
(2Z)-3-[4-(2- bromophenoxy)phenyl]-2-{[2-(4- chlorophenoxy)-2-
methylpropanoyl]amino}acrylic acid; or V00116676 562. ##STR599##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(cyclohexylacetyl)amino]acrylic acid; or V00116643 563. ##STR600##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-{[(4-
chlorophenyl)acetyl]amino}acrylic acid; 564. ##STR601##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-methylphenyl)acetyl]amino}acrylic acid; 565. ##STR602##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-bromophenyl)acetyl]amino}acrylic acid; 566. ##STR603##
(2Z)-2-{[(4-bromophenyl)acetyl]amino)-3-
[4-(2-iodophenoxy)phenyl]acrylic acid; 567. ##STR604##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[1-(4-
methylphenyl)cyclopropyl]carbonyl}amino) acrylic acid; or V00116670
568. ##STR605## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-
(4-fluorophenyl)propanoyl]amino}acrylic acid; 569. ##STR606##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{(3-
(4-chlorophenyl)propanoyl]amino}acrylic acid; 570. ##STR607##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-(3-
methoxyphenyl)propanoyl]amino)acrylic acid; 571. ##STR608##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-
(4-methylphenyl)propanoyl]amino)acrylic acid; 572. ##STR609##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-(4-
methoxyphenyl)propanoyl]amino}acrylic acid; 573. ##STR610##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({3-[3-
(trifluoromethoxy)phenyl]propanoyl}amino) acrylic acid; 574.
##STR611## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(4-
methylcyclohexyl)acetyl]amino}acrylic acid; 575. ##STR612##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-{[(4-
methylcyclohexyl)acetyl]amino}acrylic acid; 576. ##STR613##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
cyclopentylhexanoyl)amino]acrylic acid; or V00116617 577.
##STR614## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3-methyloctahydropentalen-1- yl)carbonyl]amino}acrylic acid;
578. ##STR615## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2-
(6-chloro-2,3-dihydro-1H-inden-5- yl)butanoyl]amino}acrylic acid;
579. ##STR616## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-
chloro-2-fluoro-6- (trifluoromethyl)benzoyl]amino}acrylic acid; or
V00116704 580. ##STR617## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(2-phenoxyphenyl)acetyl]amino}acrylic acid; 581. ##STR618##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2- methyl-2-(2-
naphthyloxy)propanoyl]amino}acrylic acid; 582. ##STR619##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(tricyclo[3.2.1.0.sup.2,4]oct-3- ylcarbonyl)amino]acrylic acid;
583. ##STR620## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[4-
(2,3-dihydro-1H-inden-1- yl)butanoyl]amino}acrylic acid; 584.
##STR621## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
[(2',3'-dihydrospiro[cyclopentane-1,1'-
inden]-3-ylacetyl)amino]acrylic acid; 585. ##STR622##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[4-
(cyclopentyloxy)benzoyl]amino}acrylic acid; 586. ##STR623##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(3-
phenylpentanoyl)amino]acrylic acid; 587. ##STR624##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-phenoxyphenyl)acetyl]amino}acrylic acid; or V00116652 588.
##STR625## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2-
(phenylthio)benzoyl]amino}acrylic acid; 589. ##STR626##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- {[(4-fluorophenyl)acetyl]am
ino}acrylic acid; 590. ##STR627##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-iodophenyl)acetyl]amino}acrylic acid; 591. ##STR628##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[4-
(methylthio)phenyl]acetyl}amino)acrylic acid; 592. ##STR629##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-({[4-
(trifluoromethoxy)phenyl]acetyl}amino) acrylic acid; 593.
##STR630## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3-chlorophenyl)acetyl]amino}acrylic acid; 594. ##STR631##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3-bromophenyl)acetyl]amino}acrylic acid; 595. ##STR632##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-methoxyphenyl)acetyl]amino}acrylic acid; 596. ##STR633##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-methylcyclohexyl)acetyl]amino}acrylic acid; or V00116660 597.
##STR634## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(4-methylcyclohexyl)acetyl]amino}acrylic acid; or V00116660 598.
##STR635## (2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(4-
methylcyclohexyl)acetyl]amino}acrylic acid; 599. ##STR636##
(2Z)-3-[4-(2-iodophenoxy)phenyl]-2-{[(4-
methylcyclohexyl)acetyl]amino}acrylic acid; 600. ##STR637##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3,5-dimethylphenyl)acetyl]amino}acrylic acid; or V00116651 601.
##STR638## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2-
(2-methyl-2,3-dihydro-1-benzofuran-5- yl)propanoyl]amino}acrylic
acid; 602. ##STR639## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(2-chloroquinolin-4- yl)carbonyl]amino}acrylic acid; 603.
##STR640## (2Z)-2-[(1-benzothien-4-ylacetyl)amino]-3-
[4-(2-bromophenoxy)phenyl]acrylic acid; 604. ##STR641##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[(2-
methylcyclohexyl)carbonyl]amino}acrylic acid; or V00116669 605.
##STR642## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[2-
methyl-2-(2-methyl-2,3-dihydro-1-
benzofuran-5-yl)propanoyl]amino}acrylic acid; 606. ##STR643##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
({[4-(3-methylphenyl)-1,3-thiazol-2- yl]carbonyl)amino)acrylic
acid;
607. ##STR644## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(1-methyl-3-phenyl-1H-pyrazol-5- yl)carbonyl]amino}acrylic acid;
608. ##STR645## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(3-iSopropyl-1- methylcyclopentyl)carbonyl]amino}acrylic acid;
609. ##STR646## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(5-methyl-2-phenyl-1,3-oxazol-4- yl)carbonyl]amino}acrylic acid;
610. ##STR647## (2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-{[3-
(4-fluorophenyl)propanoyl]amino)acrylic acid; 611. ##STR648##
(2Z)-2-{[3-(4- fluorophenyl)propanoyl]amino}-3-[4-(2-
iodophenoxy)phenyl]acrylic acid; 612. ##STR649##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-{[3-
(4-chlorophenyl)propanoyl]amino}acrylic acid; 613. ##STR650##
(2Z)-2-{[3-(4- chlorophenyl)propanoyl]amino)-3-[4-(2-
iodophenoxy)phenyl]acrylic acid; 614. ##STR651##
(2Z)-3-{4-[(2-bromophenyl)thio]phenyl]-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 615. ##STR652##
(2Z)-3-[5-(2-chlorophenyl)thien-2-yl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 616. ##STR653##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-methylphenoxy)phenyl]acrylic acid; 617. ##STR654## sodium
(2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-[4-(2-
methylphenoxy)phenyl]acrylate; 618. ##STR655##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
{4-[2-(methylthio)phenoxy]phenyl}acrylic acid; 619. ##STR656##
sodium (2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-{4-[2-
(methylthio)phenoxylphenyl}acrylate; 620. ##STR657##
(2Z)-3-[4-(2-chloro-6- methylphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 621. ##STR658##
(2Z)-3-[4-(2-chlorophenoxy)phenyl]-2-({[1-(4-
chlorophenyl)cyclopentyl]carbonyl}amino) acrylic acid; 622.
##STR659## (2Z)-2-({[1-
(4-chlorophenyl)cyclopentyl]carbonyl}amino)-
3-[4-(2-iodophenoxy)phenyl]acrylic acid; 623. ##STR660##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
({[3-(4-chlorophenyl)-5-methylisoxazol-4- yl]carbonyl}amino)acrylic
acid; 624. ##STR661## (2Z)-2-{[(1,3-benzothiazol-2-
yloxy)acetyl]amino}-3-[4-(2- bromophenoxy)phenyl]acrylic acid; 625.
##STR662## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-
{[(1-phenyl-1H-pyrrol-2- yl)carbonyl]amino}acrylic acid; 626.
##STR663## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-{[3-
(2,3-dihydro-1H-inden-1- yl)propanoyl]amino}acrylic acid; 627.
##STR664## (2Z)-N-(aminosulfonyl)-3-[4-(2-
bromophenoxy)phenyl]-2-[(3- cyclopentylpropanoyl)amino]acrylamide;
628. ##STR665## (2Z)-3-[4-(2-bromo-4- fluorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 629. ##STR666## sodium
(2Z)-3-[4-(2-bromo-4- fluorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylate; 630. ##STR667##
(2Z)-3-[4-(2-bromo-5- fluorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 631. ##STR668##
(2Z)-3-[3-(2-chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 632. ##STR669##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[(2
6-dichlorophenyl)thio]phenyl}acrylic acid; 633. ##STR670##
(2Z)-3-{5-[(2-bromophenyl)thio]thien-2-yl}-
2-[(3-cyclopentylpropanoyl)amino]acrylic acid; 634. ##STR671##
(2Z)-3-(2'-chloro-4-fluoro-1,1'-biphenyl-3- yl)-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 635. ##STR672##
(2Z)-3-[2-(2-chlorophenyl)-1,3-thiazol-5- yl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 636. ##STR673##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- (5-phenyl-2-furyl)acrylic
acid; 637. ##STR674## (2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
(5-phenylthien-2-yl)acrylic acid; 638. ##STR675##
(2Z)-3-[5-(2-chlorophenyl)-2-furyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 639. ##STR676##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-methoxyphenoxy)phenyl]acrylic acid; 640. ##STR677##
(2Z)-3-[4-(2-bromophenoxy)phenyl]-2- [(2,3-dihydro-1-benzofuran-5-
ylcarbonyl)amino]acrylic acid; 641. ##STR678## methyl
(2Z)-2-({[1-(4- chlorophenyl)cyclopentyl]carbonyl}amino)-
3-[4-(2-iodophenoxy)phenyl]acrylate; 642. ##STR679##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[2-
(trifluoromethoxy)phenoxy]phenyl}acrylic acid; 643. ##STR680##
(2Z)-3-[4-(2-bromo-4- chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 644. ##STR681##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-ethylphenoxy)phenyl]acrylic acid; 645. ##STR682##
(2Z)-3-[4-(2-bromo-4- cyanophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 646. ##STR683##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- (4-phenoxyphenyl)acrylic
acid; 647. ##STR684## (2Z)-3-[4-(2-bromophenoxy)phenyl]-2-[(2-
ethoxybenzoyl)amino]acrylic acid; or V00116680 648. ##STR685##
(2Z)-3-[4-(2-bromo-4- methylphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 649. ##STR686##
O-(2-chlorophenyl)-N-(3- cyclopentylpropanoyl)tyrosine; 650.
##STR687## (2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-isopropoxyphenoxy)phenyl]acrylic acid; 651. ##STR688##
(2Z)-3-[3-chloro-4-(2- chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 652. ##STR689##
(2Z)-3-[4-(2-chlorophenoxy)-3- methylphenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 653. ##STR690##
(2Z)-3-[4-(2-chlorophenoxy)-3- nitrophenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 654. ##STR691##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,3-dichlorophenoxy)phenyl]acrylic acid; 655. ##STR692##
(2Z)-3-{4-[2-chloro-3- (trifluoromethyl)phenoxy]phenyl}-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 656. ##STR693##
(2Z)-3-[4-(2-chlorophenoxy)-2- (trifluoromethyl)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 657. ##STR694##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- [4-phenoxy-2-
(trifluoromethyl)phenyl]acrylic acid; 658. ##STR695##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,4-dibromophenoxy)phenyl]acrylic acid; 659. ##STR696##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- (4-hydroxyphenyl)acrylic
acid; 660. ##STR697## 4-{(Z)-2-carboxy-2-[(3-
cyclopentylpropanoyl)amino]vinyl}benzoic acid; 661. ##STR698##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,3-difluorophenoxy)phenyl]acrylic acid; 662. ##STR699##
(2Z)-3-[3-bromo-4-(2- bromophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 663. ##STR700##
(2Z)-3-[4-(1,1'-biphenyl-2-yloxy)phenyl]-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 664. ##STR701##
(2Z)-3-[4-(4-chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 665. ##STR702##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- (1-naphthyl)acrylic acid;
666. ##STR703## (2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
(2-naphthyl)acrylic acid; 667. ##STR704##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[2-
(trifluoromethyl)phenoxy]phenyl}acrylic acid; 668. ##STR705##
sodium (2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-{4-[2-
(trifluoromethyl)phenoxy]phenyl}acrylate; 669. ##STR706##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[2-fluoro-3-
(trifluoromethyl)phenoxy]phenyl}acrylic acid; 670. ##STR707##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,3-dimethoxyphenoxy)phenyl]acrylic acid; 671. ##STR708##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-isobutylphenoxy)phenyl]acrylic acid; 672. ##STR709##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
{4-[(2,2-dimethyl-2,3-dihydro-1- benzofuran-7-yl)oxy]phenyl}acrylic
acid; 673. ##STR710## (2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-morpholin-4- ylphenoxy)phenyl]acrylic acid; 674. ##STR711##
(2Z)-3-{4-[(3-chlorobenzyl)oxyjphenyl}-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 675. ##STR712## sodium
(2Z)-3-{4-[(3- chlorobenzyl)oxy]phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylate; 676. ##STR713##
(2Z)-3-[4-(2-chloro-4- methoxyphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 677. ##STR714##
(2Z)-3-[4-(2-cyclopentylphenoxy)phenyl]-
2-[(3-cyclopentylpropanoyl)amino]acrylic acid; 678. ##STR715##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2-nitrophenoxy)phenyl]acrylic acid; 679. ##STR716##
(2Z)-3-[4-(2-tert-butylphenoxy)phenyl]-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 680. ##STR717##
(2Z)-3-{4-[(2-chlorophenyl)amino]phenyl}-
2-[(3-cyclopentylpropanoyl)amino]acrylic acid; 681. ##STR718##
(2Z)-3-{4-[(2- chlorophenyl)(methyl)amino]phenyl}-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 682. ##STR719##
(2Z)-3-[4-(4-chloro-2- methylphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 683. ##STR720##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- [4-(4-fluoro-2-
methylphenoxy)phenyl]acrylic acid; 684. ##STR721##
4-(4-{(Z)-2-carboxy-2-[(3-
cyclopentylpropanoyl)amino]vinyl}phenoxy)-3-methoxybenzoic acid;
685. ##STR722## (2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,4-dichlorophenoxy)phenyl]acrylic acid; 686. ##STR723##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
[4-(2,3-dimethylphenoxy)phenyl]acrylic acid; 687. ##STR724## sodium
(2Z)-2-[(3- cyclopentylpropanoyl)amino]-3-[4-(2,3-
dimethylphenoxy)phenyl]acrylate; 688. ##STR725##
(2Z)-2-(benzoylamino)-3-{4-[(2- oxocyclohexyl)oxy]phenyl]acrylic
acid;
689. ##STR726## (2Z)-2-(benzoylamino)-3-{4-[(2-
hydroxycyclohexyl)oxy]phenyl}acrylic acid; 690. ##STR727##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
{4-[(2-oxocyclohexyl)oxy]phenyl]acrylic acid; 691. ##STR728##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[(2-
hydroxycyclohexyl)oxy]phenyl}acrylic acid; 692. ##STR729##
(2Z)-2-(benzoylamino)-3-[4- (cyclohexyloxy)phenyl]acrylic acid;
693. ##STR730## (2Z)-3-[4-(cyclohexyloxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 694. ##STR731##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- {4-[4-nitro-2-
(trifluoromethyl)phenoxy]phenyl}acrylic acid; 695. ##STR732##
(2Z)-3-{4-[4-amino-2- (trifluoromethyl)phenoxy]phenyl}-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 696. ##STR733## sodium
(2Z)-3-{4-[4-amino-2- (trifluoromethyl)phenoxy]phenyl}-2-[(3-
cyclopentylpropanoyl)amino]acrylate; 697. ##STR734##
(2Z)-3-[4-(4-cyano-2- methoxyphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 698. ##STR735##
(2Z)-3-{4-[(3-chloropyridin-2- yl)oxy]phenyl}-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 699. ##STR736##
(2Z)-3-(4-{[3-chloro-5-
(trifluoromethyl)pyridin-2-yl]oxy}phenyl)-2-
[(3-cyclopentylpropanoyl)amino]acrylic acid; 700. ##STR737##
(2Z)-3-{4-[(3-cyanopyridin-2- yl)oxy]phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 701. ##STR738##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3- [4-(2-methoxy-4-
methylphenoxy)phenyl]acrylic acid; 702. ##STR739##
(2Z)-3-[4-(4-bromo-2- chlorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 703. ##STR740##
(2Z)-3-[4-(2-tert-butyl-4- methylphenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 704. ##STR741##
(2Z)-3-[4-(2-chloro-4- fluorophenoxy)phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 705. ##STR742##
(2Z)-3-{4-[(3-bromopyridin-2- yl)oxy]phenyl]-2-[(3-
cyclopentylpropanoyl)amino]acrylic acid; 706. ##STR743##
(2Z)-3-[6-(2-bromophenoxy)pyridin-3-yl]-
2-[(3-cyclopentylpropanoyl)amino]acrylic acid; 707. ##STR744##
(2Z)-2-[(3-cyclopentylpropanoyl)amino]-3-
(6-phenoxypyridin-3-yl)acrylic acid; 708. ##STR745##
(2Z)-2-(benzoylamino)-3-{4-[(3-
bromopyridin-2-yl)oxy]phenyl}acrylic acid; 709. ##STR746##
(2Z)-2-(benzoylamino)-3-[6-(2- bromophenoxy)pyridin-3-yl]acrylic
acid; 710. ##STR747## methyl (2Z)-2-[(3-
cyclopentylpropanoyl)amino]-3-{4-[(3-
methoxybenzyl)oxy]phenyl}acrylate 711. ##STR748## methyl
(2Z)-2-{[3-(acetyloxy)-2- methylbenzoyl]amino}-3-[4-(2-
bromophenoxy)phenyl]acrylate
* * * * *