2-(2-Hydroxybiphenyl-3-yl)-1H-Benzoimidazole-5-Carboxamidine Derivatives as Factor VIIA Inhibitors

1 . (canceled)

2 . (canceled)

3 . (canceled)

4 . (canceled)

5 . 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 having the structure of Formula I:

wherein:

R 3 is —CONR 7 R 8 (where R 7 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, sulfoalkyl or phosphonoalkyl and R 8 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, carboxyalkyl, sulfoalkyl, phosphonoalkyl, aminocarboxyalkyl, aminocarbonylcarboxyalkyl, trimethylammonioalkyl, aminocarbonylalkyl, -(alkylene)-(OCH 2 CH 2 ) n R b (where n is an integer from 1 to 6 and R b is hydrogen, alkyl, hydroxy, alkoxy, amino or alkylcarbonylamino), aryl, aralkyl, heteroaryl, heteroaralkyl, hetereocycloalkylalkyl hetereocycloalkylaminocarbonylalkyl or 3-heterocycloalkyl-2-hydroxypropyl or R 7 and R 8 together with the nitrogen atom to which they are attached form heterocycloalkylamino), -(alkylene)-CONR 9 R 10 (where R 9 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, carboxyalkyl, sulfoalkyl or phosphonoalkyl and R 10 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, carboxyalkyl, sulfoalkyl, phosphonoalkyl, aminocarboxyalkyl, aminocarbonylcarboxyalkyl, trimethylammonioalkyl, aminocarbonylalkyl, -(alkylene)-(OCH 2 CH 2 ) n R b (where n is an integer from 1 to 6 and R b is hydrogen, alkyl, hydroxy, alkoxy, amino or alkylcarbonylamino), aryl, aralkyl, heteroaryl, heteroaralkyl, hetereocycloalkylalkyl, hetereocycloalkylaminocarbonylalkyl or 3-heterocycloalkyl-2-hydroxypropyl or R 9 and R 10 together with the nitrogen atom to which they are attached form heterocycloalkylamino), —CONHSO 2 R 11 (where R 11 is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, or heterocycloalkylalkyl), or -(alkylene)-CONHSO 2 R 11 (where R 11 is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, or heterocycloalkylalkyl); and

R z is hydrogen, alkyl, haloalkyl, cycloalkyl, alkylthio, halo, hydroxy, hydroxyalkyl, nitro, cyano, alkoxy, alkoxyalkyl, alkoxyalkyloxy, hydroxyalkyloxy, aminoalkyloxy, carboxyalkyloxy, aminocarbonylalkyloxy, haloalkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonyl, heteroarylsulfonyl, carbamimidoyl, hydroxycarbamimidoyl, alkoxycarbamimidoyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, alkoxysulfonylamino, alkoxysulfonylaminoalkyl, heterocycloalkylalkylaminocarbonyl, hydroxyalkoxyalkylaminocarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonylalkyl heterocycloalkyl, heterocycloalkylalkyl, oxoheterocycloalkyl, oxoheterocycloalkylalkyl, heteroaryl, heteroaralkyl, ureido, alkylureido, dialkylureido, ureidoalkyl, alkylureidoalkyl, dialkylureidoalkyl thioureido, thioureidoalkyl, —COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), -(alkylene)-COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), —CONR 14 R 15 (where R 14 is hydrogen or alkyl and R 15 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 14 and R 15 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-CONR 16 R 17 (where R 16 is hydrogen, alkyl or hydroxyalkyl and R 17 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 14 and R 15 together with the nitrogen atom to which they are attached from heterocycloamino), —NR 18 R 19 (where R 18 is hydrogen or alkyl and R 19 is hydrogen, alkyl, acyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-NR 2 OR 21 (where R 20 is hydrogen, alkyl, or hydroxyalkyl and R 21 is hydrogen, alkyl, acyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl), —SO 2 NR 22 R 23 (where R 22 is hydrogen or alkyl and R 23 is hydrogen, 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 hydrogen, alkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 24 and R 25 together with the nitrogen atom to which they are attached from heterocycloamino), —NR 26 SO 2 NR 27 R 28 (where R 26 and R 27 are independently hydrogen or alkyl, and R 28 is hydrogen, 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 31 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 aralkyl; 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, alkoxyalkyl, alkoxycarbonylalkyl, acyl, aryl, or haloalkyl; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

6 - 10 . (canceled)

11 . The method of claim 5 , wherein the compound of Formula I is selected from:

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-succinamic;

({2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-carboxymethyl-amino)-acetic acid;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-succinic acid;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-pyrrolidine-2-carboxamide;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-4-hydroxy-pyrrolidine-2-carboxylic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N,N-dimethyl-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-hydroxy-1-hydroxymethyl-ethyl)-acetamide;

{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-acetic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-carbamoylmethyl-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-dimethylamino-ethyl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(3-dimethylamino-propyl)-acetamide;

3-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-propionic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-methyl-N-{2-[2-(2-methylamino-ethoxy)-ethoxy]-ethyl}-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(S,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,21-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-methyl-N-(2,3,4,5,6-pentahydroxy-hexyl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-methyl-acetamide;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-succinamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-[(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl)-methyl]-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-{3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl}-acetamide;

(2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-ethyl)-phosphonic acid;

{2-[{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-(2-phosphono-ethyl)-amino]-ethyl}-phosphonic acid;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinamic acid;

({2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionyl}-carboxymethyl-amino)-acetic acid;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinic acid;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionyl}-pyrrolidine-2-carboxamide;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionyl}-4-hydroxy-pyrrolidine-2-carboxylic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N,N-dimethyl-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-hydroxy-1-hydroxymethyl-ethyl)-isobutyramide;

{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-acetic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-carbamoylmethyl-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-dimethylamino-ethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(3-dimethylamino-propyl)-isobutyramide;

3-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-propionic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-methyl-N-{2-[2-(2-methylamino-ethoxy)-ethoxy]-ethyl}-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-methyl-N-(2,3,4,5,6-pentahydroxy-hexyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5-sulfamoyl-biphenyl-3-yl]-N-methyl-isobutyramide;

2S-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-[(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl)-methyl]-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-{3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl}-isobutyramide;

(2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionylamino}-ethyl)-phosphonic acid;

{2-[{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-2-methyl-propionyl}-(2-phosphono-ethyl)-amino]-ethyl}-phosphonic acid;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinamic acid;

({2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionyl}-carboxymethyl-amino)-acetic acid;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinic acid;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionyl}-pyrrolidine-2-carboxamide;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionyl}-4-hydroxy-pyrrolidine-2-carboxylic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N,N-dimethyl-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(2-hydroxy-1-hydroxymethyl-ethyl)-isobutyramide;

{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-acetic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-carbamoylmethyl-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(2-dimethylamino-ethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(3-dimethylamino-propyl)-isobutyramide;

3-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-propionic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-methyl-N-{2-[2-(2-methylamino-ethoxy)-ethoxy]-ethyl}-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-methyl-N-(2,3,4,5,6-pentahydroxy-hexyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-methyl-isobutyramide;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-succinamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-[(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl)-methyl]-isobutyramide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-N-{3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl}-isobutyramide;

(2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionylamino}-ethyl)-phosphonic acid;

{2-[{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-ureidomethyl-biphenyl-3-yl]-2-methyl-propionyl}-(2-phosphono-ethyl)-amino]-ethyl}-phosphonic acid;

2-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-succinamic acid;

{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-carboxymethyl-amino}-acetic acid;

2-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-succinic acid;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-pyrrolidine-2-carboxylic acid;

1-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetyl}-4-hydroxy-pyrrolidine-2-carboxylic acid;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-N,N-dimethyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(2-hydroxy-1-hydroxymethyl-ethyl)-5′-sulfamoyl-biphenyl-3-carboxamide;

{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-acetic acid;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-N-carbamoylmethyl-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(2-dimethylamino-ethyl)-5′-sulfamoyl-biphenyl-3-carboxamide;

3-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-propionic acid;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-methyl-N-{2-[2-(2-methylamino-ethoxy)-ethoxy]-ethyl}-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl)-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl)-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-methyl-N-(2,3,4,5,6-pentahydroxy-hexyl)-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-methyl-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-[(2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl)-methyl]-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-{3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl}-5′-sulfamoyl-biphenyl-3-carboxamide;

(2-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-ethyl)-phosphonic acid;

{2-[[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-(2-phosphono-ethyl)-amino]-ethyl}-phosphonic acid;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N,N-bis-(2-hydroxy-ethyl)-5′-methyl-biphenyl-3-carboxyamide;

(2-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-ethyl)-trimethyl-ammonium;

2-{5-[4-(2-amino-ethyl)-piperazine-1-carbonyl]-2,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl}-1H-benzoimidazole-5-carboxamidine;

2-amino-6-{[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-amino}-hexanoic acid;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-hydroxy-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N,N-dimethyl-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carboxamide;

1-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-pyrrolidine-2-carboxamide;

2-[2,2′-dihydroxy-5-(morpholine-4-carbonyl)-5′-sulfamoyl-biphenyl-3-yl]-1H-benzoimidazole-5-carboxamidine;

1-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-pyrrolidine-2-carboxylic acid;

[(2-{4-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-carbonyl]-piperazin-1-yl}-ethylamino)-dimethylamino-methylene]-dimethyl-ammonium;

2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-ethanesulfonic acid;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-morpholin-4-yl-ethyl)-acetamide;

2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetamide;

2-amino-6-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-hexanoic acid;

2-{2,2′-dihydroxy-5-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-5′-sulfamoyl-biphenyl-3-yl}-1H-benzoimidazole-5-carboxamidine;

(2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-ethyl)-trimethyl-ammonium;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-carbamoylmethyl-methyl-5′-sulfamoyl-biphenyl-3-carboxamide;

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-(2-piperazin-1-yl-ethyl)-5′-sulfamoyl-biphenyl-3-carboxamide; and

5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-N-methyl-5′-sulfamoyl-biphenyl-3-carboxamide.

12 . The method of claim 5 wherein the compound of Formula I has the structure:

R 3 is —CONR 7 R 8 (where R 7 is hydrogen, alkyl, alkoxyalkyl, carboxyalkyl, hydroxyalkyl or phosphonoalkyl and R 8 is hydrogen, alkyl, alkoxyalkyl, -(alkylene)-(OCH 2 CH 2 ) n R b (where n is an integer from 1 to 6 and R b is hydrogen, alkyl, hydroxy, alkoxy, amino or alkylcarbonylamino), aminoalkyl, aminocarbonylalkyl, aminocarbonylcarboxyalkyl, aminocarboxyalkyl, carboxyalkyl, hydroxyalkyl, phosphonoalkyl, sulfoalkyl, trimethylammonioalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or hetereocycloalkylalkyl or R 7 and R 8 together with the nitrogen atom to which they are attached form heterocycloalkylamino), -(alkylene)-CONR 9 R 10 (where R 9 is hydrogen, alkyl, alkoxyalkyl, carboxyalkyl, hydroxyalkyl or phosphonoalkyl and R 10 is hydrogen, alkyl, alkoxyalkyl, -(alkylene)-(OCH 2 CH 2 ), R b (where n is an integer from 1 to 6 and R b is hydrogen, alkyl, hydroxy, alkoxy, amino or alkylcarbonylamino), aminoalkyl, aminocarbonylalkyl, aminocarbonylcarboxyalkyl, aminocarboxyalkyl, carboxyalkyl, hydroxyalkyl, phosphonoalkyl, sulfoalkyl, trimethylammonioalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, or heterocycloalkylalkyl or R 9 and R 10 together with the nitrogen atom to which they are attached form heterocycloalkylamino), —CONHSO 2 R 11 (where R 11 is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclalkyl, or heterocycloalkylalkyl), or -(alkylene)-CONHSO 2 R 11 (where R 11 is alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, or heterocycloalkylalkyl), wherein any rings comprising R 3 are optionally substituted with one to six groups independently selected from hydroxy, hydroxyalkyl, alkoxyalkyl, carboxy, alkoxycarbonyl, aminoalkyl, guanidinoalkyl, alkyl or —CONR a R b where R a and R b are independently hydrogen or alkyl; and

R z is hydrogen, alkyl, haloalkyl, cycloalkyl, alkylthio, halo, hydroxy, hydroxyalkyl, nitro, cyano, alkoxy, alkoxyalkyl, alkoxyalkyloxy, hydroxyalkyloxy, aminoalkyloxy, carboxyalkyloxy, aminocarbonylalkyloxy, haloalkoxy, carboxy, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, cyanoalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonyl, heteroarylsulfonyl, carbamimidoyl, hydroxycarbamimidoyl, alkoxycarbamimidoyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, alkoxysulfonylamino, alkoxysulfonylaminoalkyl, heterocycloalkylalkylaminocarbonyl, hydroxyalkoxyalkylaminocarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonylalkyl, heterocycloalkyl, heterocycloalkylalkyl, oxoheterocycloalkyl, oxoheterocycloalkylalkyl, heteroaryl, heteroaralkyl, ureido, alkylureido, dialkylureido, ureidoalkyl, alkylureidoalkyl, dialkylureidoalkyl, thioureido, thioureidoalkyl, —COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), -(alkylene)-COR 12 (where R 12 is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or aminoalkyl), —CONR 14 R 15 (where R 14 is hydrogen or alkyl and R 15 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 14 and R 5 together with the nitrogen atom to which they are attached from heterocycloamino), -(alkylene)-CONR 16 R 17 (where R 16 is hydrogen, alkyl or hydroxyalkyl and R 17 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 14 and R 15 together with the nitrogen atom to which they are attached from heterocycloamino), —NR 18 R 19 (where R 12 is hydrogen or alkyl and R 19 is hydrogen, alkyl, acyl, aryl, aralkyl, heteroaryl, or heteroaralkyl), -(alkylene)-NR 2 OR 21 (where R 20 is hydrogen, alkyl, or hydroxyalkyl and R 21 is hydrogen, alkyl, acyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl), —SO 2 NR 22 R 23 (where R 22 is hydrogen or alkyl and R 23 is hydrogen, 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 hydrogen, alkyl, aryl, aralkyl, heteroaryl or heteroaralkyl or R 24 and R 25 together with the nitrogen atom to which they are attached from heterocycloamino), —NR 26 SO 2 NR 27 R 28 (where R 26 and R 27 are independently hydrogen or alkyl, and R 28 is hydrogen, 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 3 OR 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 aralkyl; 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; or

a pharmaceutically acceptable salt thereof.

13 . The method of claim 12 , wherein the compound of Formula I has the structure:

R 3 is —CONR 7 R 8 , —CH 2 CONR 9 R 10 or —C(CH 3 ) 2 CONR 9 R 10 ;

R 7 and R 8 or R 9 and R 10 both are hydrogen, carboxymethyl, 2-hydroxyethyl or 2-phosphonoethyl; or

R 7 and R 9 is hydrogen or methyl and R 8 and R 10 , respectively, is aminocarbonylmethyl, 1,2-diaminocarbonylethyl, 2-aminocarbonyl-1-carboxyethyl, 5-amino-5-carboxypentyl, 2-carboxyethyl, carboxymethyl, 2-carboxy-3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl, dimethylaminomethyl, 3-dimethylaminopropyl, 2-hydroxy-1,1-bis-hydroxymethyl-ethyl, 2-hydroxy-1-hydroxymethylethyl, 1,2-dicarboxyethyl, methyl, 2-[2-(2-methylaminoethoxy)ethoxy]ethyl, 2-(4-methylpiperazin-1-yl)ethyl, 2-morpholin-4-ylethyl, 2,3,4,5,6-pentahydroxy-hexyl, 2-piperazin-1-ylethyl, 2-sulfoethyl, 3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl-methyl, trimethylammonioethyl or 2-phosphonoethyl or R 7 and R 8 or R 9 and R 10 together with the nitrogen atom to which they are attached form 2-aminocarbonylpyrrolidin-1-yl, 2-carboxy-4-hydroxypyrrolidin-1-yl or 4-methylpiperazin-1-yl;

and R z is aminosulfonyl or ureidomethyl; or a pharmaceutically acceptable salt thereof.

14 . The method of claim 5 , wherein the compound of Formula I has the structure:

wherein:

R 3 is —CONR 7 R 8 , —CH 2 CONR 9 R 10 or —C(CH 3 ) 2 CONR 9 R 10 ;

R 7 is hydrogen or methyl;

R 9 is hydrogen or methyl;

R 8 is aminocarbonylmethyl, 1,2-diaminocarbonylethyl, 2-aminocarbonyl-1-carboxyethyl, 5-amino-5-carboxypentyl, 2-carboxyethyl, carboxymethyl, 2-carboxy-3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl, dimethylaminomethyl, 3-dimethylaminopropyl, 2-hydroxy-1,1-bis-hydroxymethyl-ethyl, 2-hydroxy-1-hydroxymethylethyl, 1,2-dicarboxyethyl, methyl, 2-[2-(2-methylaminoethoxy)ethoxy]ethyl, 2-(4-methylpiperazin-1-yl)ethyl, 2-morpholin-4-ylethyl, 2,3,4,5,6-pentahydroxy-hexyl, 2-piperazin-1-ylethyl, 2-sulfoethyl, 3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl-methyl, trimethylammonioethyl or 2-phosphonoethyl;

R 10 is aminocarbonylmethyl, 1,2-diaminocarbonylethyl, 2-aminocarbonyl-1-carboxyethyl, 5-amino-5-carboxypentyl, 2-carboxyethyl, carboxymethyl, 2-carboxy-3-[2-(2-ethoxy-ethoxy)-ethoxy]-propyl, dimethylaminomethyl, 3-dimethylaminopropyl, 2-hydroxy-1,1-bis-hydroxymethyl-ethyl, 2-hydroxy-1-hydroxymethylethyl, 1,2-dicarboxyethyl, methyl, 2-[2-(2-methylaminoethoxy)ethoxy]ethyl, 2-(4-methylpiperazin-1-yl)ethyl, 2-morpholin-4-ylethyl, 2,3,4,5,6-pentahydroxy-hexyl, 2-piperazin-1-ylethyl, 2-sulfoethyl, 3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl, 2,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-ylcarbamoyl-methyl, trimethylammonioethyl or 2-phosphonoethyl;

R z is aminosulfonyl or ureidomethyl;

R 13 is hydrogen; or

a pharmaceutically acceptable salt thereof.

15 . The method of claim 14 , wherein the compound of Formula I has the structure:

R 3 is —CONR 7 R 8 , —CH 2 CONR 9 R 10 or —C(CH 3 ) 2 CONR 9 R 10 ;

R 7 is hydrogen;

R 9 is hydrogen;

R 8 is aminocarbonylmethyl, 2-aminocarbonyl-1-carboxyethyl, 5-amino-5-carboxypentyl, 2-carboxyethyl, carboxymethyl, or 1,2-dicarboxyethyl;

R 10 is aminocarbonylmethyl, 2-aminocarbonyl-1-carboxyethyl, 5-amino-5-carboxypentyl, 2-carboxyethyl, carboxymethyl, or 1,2-dicarboxyethyl;

R z is aminosulfonyl; or

a pharmaceutically acceptable salt thereof.

16 . The method of claim 15 , wherein the compound of Formula I has the structure: 2-{2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetylamino}-succinic acid.

17 . The method of claim 5 , wherein the disease is cancer.

18 . The method of claim 5 , wherein the disease is a thromboembolic disorder associated with cancer.

19 . The method of claim 11 , wherein the disease is cancer.

20 . The method of claim 11 , wherein the disease is a thromboembolic disorder associated with cancer.

21 . The method of claim 12 , wherein the disease is cancer.

22 . The method of claim 12 , wherein the disease is a thromboembolic disorder associated with cancer.

23 . The method of claim 13 , wherein the disease is cancer.

24 . The method of claim 13 , wherein the disease is a thromboembolic disorder associated with cancer.

25 . The method of claim 14 , wherein the disease is cancer.

26 . The method of claim 14 , wherein the disease is a thromboembolic disorder associated with cancer.

27 . The method of claim 15 , wherein the disease is cancer.

28 . The method of claim 15 , wherein the disease is a thromboembolic disorder associated with cancer.

29 . The method of claim 16 , wherein the disease is cancer.

30 . The method of claim 16 , wherein the disease is a thromboembolic disorder associated with cancer.