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

1 . A compound of Formula I:

wherein:

X 1 , X 2 , X 3 , and X 4 are independently —N— or —CR 5 — wherein R 5 is hydrogen, alkyl, or halo with the proviso that not more than three of X 1 , X 2 , X 3 and X 4 are —N—;

R 1 and R 2 independently are hydrogen, alkyl, or halo;

R 3 is —COOR 9 , -(alkylene)-COOR 9 , —CR 8 (COOR 11 )alkylene-COOR 9 , or a group of formula (a):

where:

n is 0 or 1;

R 8 is hydrogen, alkyl, or hydroxy; and

R 10 is hydrogen or alkyl; or

R 8 and R 10 together form a covalent bond;

R 9 and R 11 are independently hydrogen, alkyl, haloalkyl, aryl, or aralkyl;

R 4 is hydrogen, alkyl, alkylthio, halo, hydroxy, hydroxyalkyl, alkoxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, or nitro;

R 6 is hydrogen, alkyl, or halo;

R 7 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, —COR 12 (where R 12 is alkyl or haloalkyl), -(alkylene)-COR 12 (where R 12 is alkyl or haloalkyl), aminocarbonyl, aminocarbonylalkyl, —CONR 14 R 15 (where R 14 is hydrogen or alkyl and R 15 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-CONR 16 R 17 (where R 16 is hydrogen or alkyl and R 17 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), amino, alkylamino, dialkylamino, —NR 18 R 19 (where R 18 is hydrogen or alkyl and R 19 is aryl, aralkyl, heteroaryl, or heteroaralkyl), aminoalkyl, -(alkylene)-NR 20 R 21 (where R 20 is hydrogen or alkyl and R 21 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), aminosulfonyl, —SO 2 NR 22 R 23 (where R 22 is hydrogen or alkyl and R 23 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, or R 22 and R 23 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-SO 2 NR 24 R 25 (where R 24 is hydrogen or alkyl and R 25 is alkyl, aryl, aralkyl, heteroaryl, or, heteroaralkyl or R 24 and R 25 together with the nitrogen atom to which they are attached from heterocycloamino), aminosulfonylamino, —NR 26 SO 2 NR 27 R 28 (where R 26 and R 27 are independently hydrogen or alkyl, and R 28 is alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R 27 and R 28 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-NR 29 SO 2 NR 30 R 31 (where R 29 and R 30 are independently hydrogen or alkyl, and R 31 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl or R 30 and R 31 together with the nitrogen atom to which they are attached from heterocycloamino), —CONH-(alkylene)-NR 32 R 33 where R 32 is hydrogen or alkyl and R 33 is alkyl), or -(alkenylene)-R 34 (where R 34 is alkyl, alkoxy, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, acylamino, aminosulfonylamino, alkylaminosulfonylamino, alkylsulfonyl, aryl, heteroaryl, heterocycloalkyl, heterocycloalkylcarbonyl, aminocarbonyl, aminosulfonyl, —COR 12 , —CONR 14 R 15 , —NR 18 R 19 , —SO 2 NR 22 R 23 or —NR 26 SO 2 NR 27 R 28 where R 12 , R 14 , R 15 , R 18 , R 19 R 22 , R 23 , R 26 , R 27 , and R 28 are as defined above); and

R 13 is hydrogen, hydroxy, (C 1-10 )alkoxy, —C(O)R 35 where R 35 is alkyl, aryl, haloalkyl, or cyanoalkyl, or —C(O)OR 36 where R 36 is alkyl, hydroxyalkyl, acyl, or haloalkyl; and individual isomers, mixture of isomers, or a pharmaceutically acceptable salt thereof, provided that when R 7 is hydrogen, alkyl, halo, nitro, alkoxy, haloalkyl, carboxy, alkoxycarbonyl, amino, alkylamino, dialkylamino, —NR 18 R 19 (where R 18 is hydrogen or alkyl and R 19 is aryl or aralkyl), pyrrolidinylcarbonyl, —SO 2 NR 22 R 23 (where R 22 and R 23 are alkyl), carbamimidoyl, alkylsulfonylamino, alkylthio, ureido or —NHC(S)NH 2 , and R 3 is —COOR 9 , -(alkylene)-COOR 9 , —CR 8 (COOR 11 )alkylene-COOR 9 , or a group of formula (a) where n is 0 or 1; R 8 and R 10 are independently hydrogen or alkyl, and R 13 is hydrogen; then R 4 is hydroxy or hydroxyalkyl.

2 . The compound of claim 1 wherein X 1 is —N— and X 2 , X 3 , and X 4 are —CR 5 — where R 5 is hydrogen.

3 . The compound of claim 1 wherein X 1 is —N—; X 2 and X 4 are —CR 5 — where R 5 is hydrogen and X 3 is —CR 5 — where R 5 is halo.

4 . The compound of claim 1 wherein X 1 is —CH— and X 2 , X 3 , and X 4 are —CR 5 — where R 5 is hydrogen.

5 . The compound of claim 1 wherein X 1 is —CH—; X 2 and X 4 are —CR 5 — where R 5 is hydrogen and X 3 is —CR 5 — where R 5 is halo.

7 . The compound of claim 2 where R 1 , R 2 , and R 13 are hydrogen; R 3 is a group of formula (a) where n is 0, R 8 and R 10 are hydrogen and one of R 9 and R 11 is hydrogen and the other of R 9 and R 11 is ethyl.

8 . The compound of claim 2 where R 1 , R 2 , and R 13 are hydrogen; R 3 is a group of formula (a) where n is 0, R 8 , R 9 , R 10 and R 11 are hydrogen.

9 . The compound of claim 4 where R 1 , R 2 , and R 13 are hydrogen; R 3 is a group of formula (a) where n is 0, R 8 and R 10 are hydrogen and one of R 9 and R 11 is hydrogen and the other of R 9 and R 11 is ethyl.

10 . The compound of claim 4 where R 1 , R 2 , and R 13 are hydrogen; R 3 is a group of formula (a) where n is 0, R 8 , R 9 , R 10 and R 11 are hydrogen.

11 . The compound of claim 8 wherein R 4 is hydroxy or hydroxymethyl and is located at the 2′-position of the biphenyl ring and R 6 and R 7 are hydrogen.

12 . The compound of claim 8 wherein R 4 is hydroxy and is located at the 2′-position of the biphenyl ring, R 6 is hydrogen, and R 7 is located at the 5′-position of the biphenyl ring.

13 . The compound of claim 12 wherein R 7 is alkyl, halo, hydroxy, hydroxyalkyl, carboxy, alkoxy, cyano, nitro, amino, aminocarbonyl, alkylsulfonylamino, aminoalkyl, aminosulfonyl, ureido, ureidoalkyl, alkylureidoalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl, heteroaryl, heterocycloalkylcarbonyl, heterocycloalkylalkyl, —NHSO 2 NR 27 R 28 where R 27 and R 28 are independently hydrogen or alkyl, or —COR 12 where R 12 is alkyl.

14 . The compound of claim 12 wherein R 7 is methyl, isopropyl, chloro, fluoro, hydroxy, hydroxymethyl, 2-hydroxyethyl, carboxy, methoxy, cyano, nitro, aminocarbonyl, methylsulfonylamino, aminomethyl, ureidomethyl, —CH 2 NHCONHCH 3 , imidazol-2-yl, amino, ureido, cyanomethyl, 2-cyanoethyl, carboxymethyl, 2-carboxyethyl, aminocarbonylmethyl, dimethylaminosulfonylamino, acetyl, or aminosulfonyl.

15 . The compound of claim 8 wherein R 4 is hydroxymethyl and is located at the 2′-position of the biphenyl ring, R 6 is hydrogen, and R 7 is located at the 5′-position of the biphenyl ring.

16 . The compound of claim 15 wherein R 7 is alkyl, halo, hydroxy, hydroxyalkyl, carboxy, alkoxy, cyano, nitro, amino, aminocarbonyl, alkylsulfonylamino, aminoalkyl, aminosulfonyl, ureido, ureidoalkyl, alkylureidoalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl, heteroaryl, heterocycloalkylcarbonyl, heterocycloalkylalkyl, —NHSO 2 NR 27 R 28 where R 27 and R 28 are independently hydrogen or alkyl, or —COR 12 where R 12 is alkyl.

17 . The compound of claim 15 wherein R 7 is methyl, isopropyl, chloro, fluoro, hydroxy, hydroxymethyl, 2-hydroxyethyl, carboxy, methoxy, cyano, nitro, aminocarbonyl, methylsulfonylamino, aminomethyl, ureidomethyl, —CH 2 NHCONHCH 3 , imidazol-2-yl, amino, ureido, cyanomethyl, 2-cyanoethyl, carboxymethyl, 2-carboxyethyl, aminocarbonylmethyl, dimethylaminosulfonylamino, acetyl, or aminosulfonyl.

18 . The compound of claim 8 wherein R 4 is aminosulfonyl and is located at the 2′-position of the biphenyl ring, R 6 is hydrogen, and R 7 is located at the 5′-position of the biphenyl ring.

19 . The compound of claim 18 wherein R 7 is alkyl, halo, hydroxy, hydroxyalkyl, carboxy, alkoxy, cyano, nitro, amino, aminocarbonyl, alkylsulfonylamino, aminoalkyl, aminosulfonyl, ureido, ureidoalkyl, alkylureidoalkyl, cyanoalkyl, carboxyalkyl, aminocarbonylalkyl, heteroaryl, heterocycloalkylcarbonyl, heterocycloalkylalkyl, —NHSO 2 NR 27 R 28 where R 27 and R 28 are independently hydrogen or alkyl, or —COR 12 where R 12 is alkyl.

20 . The compound of claim 18 wherein R 7 is methyl, isopropyl, chloro, fluoro, hydroxy, hydroxymethyl, 2-hydroxyethyl, carboxy, methoxy, cyano, nitro, aminocarbonyl, methylsulfonylamino, aminomethyl, ureidomethyl, —CH 2 NHCONHCH 3 , imidazol-2-yl, amino, ureido, cyanomethyl, 2-cyanoethyl, carboxymethyl, 2-carboxyethyl, aminocarbonylmethyl, dimethylaminosulfonylamino, or acetyl.

21 . The compound of claim 8 wherein R 4 and R 5 are hydrogen and R 7 is located at the 3′-position of the biphenyl ring.

22 . The compound of claim 21 wherein R 7 is aminosulfonyl, haloalkoxy, hydroxy, hydroxyalkyl, aminocarbonyl, ureidoalkyl, cyanoalkyl, alkoxyalkyl, carboxyalkyl, aminocarbonylalkyl, heterocycloalkylalkyl, —COR 12 (where R 12 is alkyl) or cyano.

23 . The compound of claim 1 wherein the moiety:

is 2′-acetylphenyl, 3′-acetylphenyl, 3′-hydroxyphenyl, 2′-hydroxyphenyl, 3′-aminocarbonylphenyl, 3′-cyanophenyl, 5′-fluoro-2′-hydroxyphenyl, 5′-chloro-2′-hydroxy-phenyl, 2′-hydroxy-methylphenyl, 5′-carboxy-2′-hydroxyphenyl, 2′,5′-dihydroxyphenyl, 5′-cyano-2′-methoxyphenyl, 5′-aminocarbonyl-2′-methoxyphenyl, 2′,6′-dihydroxyphenyl, 3′-bromo-2′,6′-dihydroxyphenyl, 2′-hydroxy-5′-nitrophenyl, 2′-cyano-phenyl, 3′-hydroxymethylphenyl, 3′-(2-hydroxyethylphenyl), 5′-cyano-2′-hydroxyphenyl, 5′-aminocarbonyl-2′-hydroxyphenyl, 5′-aminomethyl-2′-hydroxyphenyl, 2′-hydroxy-5′-ureidomethylphenyl, 2′-hydroxy-5′-imidazol-2-ylphenyl, 5′-amino-2′-hydroxyphenyl, 2′-hydroxy-5′-ureidophenyl, 2′-hydroxy-5′-(2-morpholin-4-ylethyl)aminocarbonylphenyl, 3′-bromo-2′-hydroxy-5′-cyanomethylphenyl, 5′-(2-cyanoethyl)-2′-hydroxyphenyl, 3′-bromo-5′-carboxymethyl-2′-hydroxyphenyl, 5′-(2-carboxyethyl)-2′-hydroxyphenyl, 5′-amino-carbonylmethyl-2′-hydroxyphenyl, 3′,5′-dichloro-2′-hydroxyphenyl, 2′-hydroxy-5′-[2-(2-hydroxyethoxy)-ethylaminocarbonyl]phenyl, 5′-dimethylaminosulfonylamino-2′-hydroxy-phenyl, 3′-bromo-5′-chloro-2′-hydroxyphenyl, 2′-hydroxy-5′-(4-methylpiperazin-1-ylcarbonyl)phenyl, 2′-hydroxy-5′-(4-methylpiperazin-1-ylmethyl)phenyl, 5′-amidino-2′-hydroxyphenyl, 5′-(2-dimethylaminoethylaminocarbonyl)-2′-hydroxyphenyl, 3′-amino-sulfonylphenyl, 2′-hydroxy-5′-aminosulfonylphenyl, 2′-hydroxy-5′-hydroxymethyl-phenyl, 2′-hydroxy-5′-(2-hydroxyethyl)phenyl, 2′-hydroxy-5′-dimethylaminosulfonyl-aminophenyl, 5′-aminocarbonyl-2′-hydroxy-phenyl, or 2′-hydroxy-5′-(CH 3 NHCONHCH 2 )phenyl.

24 . The compound of claim 1 wherein the moiety:

is 2′,6′-dihydroxyphenyl, 5′-fluoro-2′-hydroxyphenyl, 5′-aminocarbonyl-2′-hydroxyphenyl, 3′-aminosulfonylphenyl, 3′-ureidomethylphenyl, 2′-hydroxy-5′-hydroxymethylphenyl, or 2′-hydroxy-5′-ureidomethylphenyl.

25 . 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′-dimethylamino-sulfonylamino-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-dimethylaminoethylamino-carbonyl)-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′-methylureido-methylbiphenyl-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.

26 . A compound selected from the group consisting of:

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)-6,2′-dihydroxy-5′-hydroxymethylbiphenyl-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)-5′-aminocarbonyl-6,2′-dihydroxy-biphenyl-3-yl]-succinic acid; and

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-3′-aminosulfonyl-6-hydroxy-biphenyl-3-yl]-succinic acid;

or a pharmaceutically acceptable salt thereof.

27 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 .

28 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 25 .

29 . A method of treating a disease in an animal mediated by Factor VIIa which method comprises administering to said animal a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

30 . A method of treating a disease in an animal mediated by Factor VIIa which method comprises administering to said animal a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 25 and a pharmaceutically acceptable carrier.

31 . The method of claim 29 wherein the disorder is a thromboembolic disorder.

32 . The method of claim 30 wherein the disorder is a thromboembolic disorder.

33 . A method of treating a a thromboembolic disorder, which method comprises administering to said animal a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 in combination with another anticoagulant agent(s) independently selected from a group consisting of a thrombin inhibitor, a factor IXa, a factor Xa inhibitor, Aspirin®, and Plavis®.

34 . A method for inhibiting the coagulation of a biological sample comprising the administration of a compound of claim 1 .

35 . An intermediate of Formula II:

wherein R 1 , R 2 , R 3 , R 4 , R 6 , and R 7 are as defined in claim 1 .

36 . A process of preparing a compound of claim 1 where X 1 is —N— comprising reacting a compound of Formula II:

wherein R 1 , R 2 , R 3 , R 4 , R 6 , and R 7 are as defined in claim 1 above, with a compound of Formula II:

where R 13 is hydrogen;

optionally modifying any of the R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 13 groups;

optionally isolating individual isomers;

optionally preparing an acid addition salt; and

optionally preparing a free base.

optionally preparing an acid addition salt; and

optionally preparing a free base.