US 2003/0114457 A1Published application

2- [5- (5-carbamimidoyl-1H-heteroaryl)-6-hydroxybiphenyl-3-yl]-succinic acid derivatives as factor viia inhibitors

AssigneeAxys Pharmaceuticals, Inc.

InventorsHuiyong Hu, John Hendrix, Aleksandr Kolesnikov, Roopa Rai, William Dvorak Shrader, David Sperandio, Wendy Young, Steve Torkelson

Life of this patent

Estimating the term…

Abstract

The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders. Processes for preparing these inhibitors are also disclosed.

Claims35

Dependent claims

A compound of Formula I:

35
wherein:
X1, X2, X3, and X4 are independently —N— or —CR5— wherein R5 is hydrogen, alkyl, or halo with the proviso that not more than three of X1, X2, X3 and X4 are —N—;
R1 and R2 independently are hydrogen, alkyl, or halo;
R3 is —COOR9, -(alkylene)-COOR9, —CR8(COOR11)alkylene-COOR9, or a group of formula (a):
36
where:
n is 0 or 1;
R8 is hydrogen, alkyl, or hydroxy;
and
R10 is hydrogen or alkyl;
or
R8 and R10 together form a covalent bond;
R9 and R11 are independently hydrogen, alkyl, haloalkyl, aryl, or aralkyl;
R4 is hydrogen, alkyl, alkylthio, halo, hydroxy, hydroxyalkyl, alkoxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, or nitro;
R6 is hydrogen, alkyl, or halo;
R7 is hydrogen, alkyl, cycloalkyl, alkylthio, halo, hydroxy, nitro, cyano, alkoxy, haloalkoxy, carboxy, alkoxycarbonyl, acylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, carbamimidoyl, hydroxycarbamimidoyl, alkoxycarbamimidoyl, alkylsulfonylamino, alkoxysulfonylamino, alkylsulfonylaminoalkyl, alkoxysulfonylaminoalkyl, heterocycloalkylalkylaminocarbonyl, hydroxyalkoxyalkylaminocarbonyl, haloalkyl, cyanoalkyl, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonylalkyl, heterocycloalkyl, heterocycloalkylalkyl, oxoheterocycloalkylalkyl, aminosulfonylalkyl, heteroaryl, heteroaralkyl, ureido, alkylureido, dialkylureido, ureidoalkyl, alkylureidoalkyl, dialkylureidoalkyl, thioureido, thioureidoalkyl, —COR12 (where R12 is alkyl or haloalkyl), -(alkylene)-COR12 (where R12 is alkyl or haloalkyl), aminocarbonyl, aminocarbonylalkyl, —CONR14R15 (where R14 is hydrogen or alkyl and R15 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-CONR16R17 (where R16 is hydrogen or alkyl and R17 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), amino, alkylamino, dialkylamino, —NR18R19 (where R18 is hydrogen or alkyl and R19 is aryl, aralkyl, heteroaryl, or heteroaralkyl), aminoalkyl, -(alkylene)-NR20R21 (where R20 is hydrogen or alkyl and R21 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), aminosulfonyl, —SO2NR22R23 (where R22 is hydrogen or alkyl and R23 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, or R22 and R23 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-SO2NR24R25 (where R24 is hydrogen or alkyl and R25 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R24 and R25 together with the nitrogen atom to which they are attached from heterocycloamino), aminosulfonylamino, —NR26SO2NR27R28 (where R26 and R27 are independently hydrogen or alkyl, and R28 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R27 and R28 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-NR29SO2NR30R31 (where R29 and R30 are independently hydrogen or alkyl, and R31 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R30 and R31 together with the nitrogen atom to which they are attached from heterocycloamino), —CONH-(alkylene)-NR32R33 where R32 is hydrogen or alkyl and R33 is alkyl), or -(alkenylene)-R34 (where R34 is alkyl, alkoxy, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, acylamino, aminosulfonylamino, alkylaminosulfonylamino, alkylsulfonyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkylcarbonyl, aminocarbonyl, aminosulfonyl, —COR12, —CONR14R15, —NR18R19, —SO2NR22R23, or—NR26SO2NR27R28 where R12, R14, R15, R18 , R19, R22, R23, R26, R27, and R28 are as defined above);
and
R13 is hydrogen, hydroxy, (C1-10)alkoxy, —C(O)R35 where R35 is alkyl, aryl, haloalkyl, or cyanoalkyl, or —C(O)OR36 where R36 is alkyl, hydroxyalkyl, acyl, or haloalkyl;
and individual isomers, mixture of isomers, or a pharmaceutically acceptable salt thereof, provided that when R7 is hydrogen, alkyl, halo, nitro, alkoxy, haloalkyl, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, —NR18R19 (where R18 is hydrogen or alkyl and R19 is aryl or aralkyl), pyrrolidinylcarbonyl, —SO2NR22R23 (where R22 and R23 are alkyl), carbamimidoyl, alkylsulfonylamino, alkylthio, ureido or —NHC(S)NH2, and R3 is —COOR9, -(alkylene)-COOR9, —CR8(COOR11)alkylene-COOR9, or a group of formula (a) where n is 0 or 1;
R8 and R10 are independently hydrogen or alkyl, and R13 is hydrogen;
then R4 is hydroxy or hydroxyalkyl.

19 more elements

A compound selected from the group consisting of:

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-3′-(1,1-difluoro-methoxy)-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[3′-acetyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,3′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-3′-aminocarbonyl-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-3′-cyano-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-chloro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-2′-hydroxymethyl-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-indol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-carboxy-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′,5′-trihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-cyano-6-hydroxy-2′-methoxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-aminocarbonyl-6-hydroxy-2′-methoxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′,6′-trihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-nitro-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-2′-cyano-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(6-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-3′-hydroxymethyl-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-cyano-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-aminocarbonyl-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[3′-bromo-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′,6′-trihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-methylsulfonylamino-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-isopropyl-biphenyl-3-yl]-succinic acid;
2-[5′-aminomethyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-imidazol-2-yl-biphenyl-3-yl]-succinic acid;
2-[5′-amino-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureido-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-(2-morpholin-4-ylethylaminocarbonyl-biphenyl-3-yl]-succinic acid;
2-[3′-bromo-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-cyanomethylbiphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-(2-cyanoethyl)-6,2′-dihydroxybiphenyl-3-yl]-succinic acid;
2-[3′bromo-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-carboxymethyl-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-(2-carboxyethyl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[2′-acetyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[3′-bromo-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-aminocarbonylmethyl-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-indol-2-yl)-5′-aminocarbonyl-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-3′,5′-dichloro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-[2-(2-hydroxyethoxy)ethylaminocarbonyl]-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-4′,6′-dichloro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-dimethylaminosulfonylamino-biphenyl-3-yl]-succinic acid;
2-[3′-bromo-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-chloro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-(4-methyl-piperazin-1-ylcarbonyl)-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-(4-methyl-piperazin-1-ylmethyl)-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-carbamimidoyl-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-(2-dimethylaminoethylaminocarbonyl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-hydroxymethyl-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-methylureidomethylbiphenyl-3-yl]-succinic acid;
2-[3′-aminosulfonyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-dimethylaminosulfonyl-amino-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-6-fluoro-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-6-chloro-1H-indol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
diethyl 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinate;
2-[5-(5-carbamimidoyl-5-fluoro-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-2-methylsuccinic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid 1-ethyl ester;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid 4-ethyl ester;
(Z)-2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6-hydroxy-2′methoxy-biphenyl-3-yl]-but-2-enedioic acid;
(Z)-2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-but-2-enedioic acid;
(E)-2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-but-2-enedioic acid;
3-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-propionic acid;
methyl 3-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-propionate;
methyl 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-acetate;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-biphenyl-3-yl]-acetic acid;
2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-acetic acid;
2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid;
diethyl 2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-succinate;
2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-methylsulfonylaminobiphenyl-3-yl]-succinic acid;
diethyl 2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethylbiphenyl-3-yl]-succinate;
2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-5′-fluoro-6,2′-dihydroxy-biphenyl-3-yl]-acetic acid;
diethyl 2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-hydroxymethylbiphenyl-3-yl]-succinate;
dimethyl 2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-5′-aminocarbonyl-6,2′-dihydroxybiphenyl-3-yl]-succinate;
and
2-[5-(5-N-hydroxycarbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethylbiphenyl-3-yl]-succinic acid;
or
a pharmaceutically acceptable salt thereof.

72 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/190,147Filed 3 Jul 2002
Priority: 9 Jul 2001
Published: 19 Jun 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
C07C 69/738
Of unsaturated acids: esters of keto-carboxylic acids or aldehydo-carboxylic acids
C07C 205/56
The carbon skeleton being further substituted by carboxyl groups: having nitro groups bound to carbon atoms of six-membered aromatic rings and…

Family

Application60/303,953Us provisional application · filed 9 Jul 2001
Application60/351,054Us provisional application · filed 22 Jan 2002
US 2003/0114457 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I:

35
wherein:
X1, X2, X3, and X4 are independently —N— or —CR5— wherein R5 is hydrogen, alkyl, or halo with the proviso that not more than three of X1, X2, X3 and X4 are —N—;
R1 and R2 independently are hydrogen, alkyl, or halo;
R3 is —COOR9, -(alkylene)-COOR9, —CR8(COOR11)alkylene-COOR9, or a group of formula (a):
36
where:
n is 0 or 1;
R8 is hydrogen, alkyl, or hydroxy;
and
R10 is hydrogen or alkyl;
or
R8 and R10 together form a covalent bond;
R9 and R11 are independently hydrogen, alkyl, haloalkyl, aryl, or aralkyl;
R4 is hydrogen, alkyl, alkylthio, halo, hydroxy, hydroxyalkyl, alkoxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, or nitro;
R6 is hydrogen, alkyl, or halo;
R7 is hydrogen, alkyl, cycloalkyl, alkylthio, halo, hydroxy, nitro, cyano, alkoxy, haloalkoxy, carboxy, alkoxycarbonyl, acylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, carbamimidoyl, hydroxycarbamimidoyl, alkoxycarbamimidoyl, alkylsulfonylamino, alkoxysulfonylamino, alkylsulfonylaminoalkyl, alkoxysulfonylaminoalkyl, heterocycloalkylalkylaminocarbonyl, hydroxyalkoxyalkylaminocarbonyl, haloalkyl, cyanoalkyl, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonylalkyl, heterocycloalkyl, heterocycloalkylalkyl, oxoheterocycloalkylalkyl, aminosulfonylalkyl, heteroaryl, heteroaralkyl, ureido, alkylureido, dialkylureido, ureidoalkyl, alkylureidoalkyl, dialkylureidoalkyl, thioureido, thioureidoalkyl, —COR12 (where R12 is alkyl or haloalkyl), -(alkylene)-COR12 (where R12 is alkyl or haloalkyl), aminocarbonyl, aminocarbonylalkyl, —CONR14R15 (where R14 is hydrogen or alkyl and R15 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-CONR16R17 (where R16 is hydrogen or alkyl and R17 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), amino, alkylamino, dialkylamino, —NR18R19 (where R18 is hydrogen or alkyl and R19 is aryl, aralkyl, heteroaryl, or heteroaralkyl), aminoalkyl, -(alkylene)-NR20R21 (where R20 is hydrogen or alkyl and R21 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), aminosulfonyl, —SO2NR22R23 (where R22 is hydrogen or alkyl and R23 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, or R22 and R23 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-SO2NR24R25 (where R24 is hydrogen or alkyl and R25 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R24 and R25 together with the nitrogen atom to which they are attached from heterocycloamino), aminosulfonylamino, —NR26SO2NR27R28 (where R26 and R27 are independently hydrogen or alkyl, and R28 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R27 and R28 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-NR29SO2NR30R31 (where R29 and R30 are independently hydrogen or alkyl, and R31 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R30 and R31 together with the nitrogen atom to which they are attached from heterocycloamino), —CONH-(alkylene)-NR32R33 where R32 is hydrogen or alkyl and R33 is alkyl), or -(alkenylene)-R34 (where R34 is alkyl, alkoxy, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, acylamino, aminosulfonylamino, alkylaminosulfonylamino, alkylsulfonyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkylcarbonyl, aminocarbonyl, aminosulfonyl, —COR12, —CONR14R15, —NR18R19, —SO2NR22R23, or—NR26SO2NR27R28 where R12, R14, R15, R18 , R19, R22, R23, R26, R27, and R28 are as defined above);
and
R13 is hydrogen, hydroxy, (C1-10)alkoxy, —C(O)R35 where R35 is alkyl, aryl, haloalkyl, or cyanoalkyl, or —C(O)OR36 where R36 is alkyl, hydroxyalkyl, acyl, or haloalkyl;
and individual isomers, mixture of isomers, or a pharmaceutically acceptable salt thereof, provided that when R7 is hydrogen, alkyl, halo, nitro, alkoxy, haloalkyl, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, —NR18R19 (where R18 is hydrogen or alkyl and R19 is aryl or aralkyl), pyrrolidinylcarbonyl, —SO2NR22R23 (where R22 and R23 are alkyl), carbamimidoyl, alkylsulfonylamino, alkylthio, ureido or —NHC(S)NH2, and R3 is —COOR9, -(alkylene)-COOR9, —CR8(COOR11)alkylene-COOR9, or a group of formula (a) where n is 0 or 1;
R8 and R10 are independently hydrogen or alkyl, and R13 is hydrogen;
then R4 is hydroxy or hydroxyalkyl.

19 more elements

Facts

Application

10/190,147Filed 3 Jul 2002

Priority

9 Jul 2001

Published

19 Jun 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
C07C 69/738
Of unsaturated acids: esters of keto-carboxylic acids or aldehydo-carboxylic acids
C07C 205/56
The carbon skeleton being further substituted by carboxyl groups: having nitro groups bound to carbon atoms of six-membered aromatic rings and…