Thrombopoietin activity modulating compounds and methods

1. A compound of Formula III:

or a pharmaceutically acceptable salt, ester, or amide thereof,

wherein:

R 1 is selected from CO 2 R 10 , CONR 10 R 11 , SO 3 R 10 , and a carboxylic acid bioisostere;

R 2 and R 3 are each independently selected from null, hydrogen, OR 12 , NR 12 R 13 , an optionally substituted C 1 -C 4 aliphatic, an optionally substituted C 1 -C 4 haloaliphatic, an optionally substituted C 1 -C 4 heteroaliphatic, an optionally substituted ring, and (CH 2 ) m R 14 ; or R 2 and R 3 taken together form an optionally substituted olefin; or R 2 and R 3 are linked to form an optionally substituted C 3 -C 8 ring;

R 4 is selected from hydrogen, F, Cl, Br, C 1 -C 4 aliphatic, C 1 -C 4 haloaliphatic, C 1 -C 4 heteroaliphatic, and a ring;

R 5 is selected from hydrogen, OR 10 , SR 10 , NHR 11 , and CO 2 H;

R 6 is selected from hydrogen, OR 12 , NR 12 R 13 , F, Cl, Br, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 heteroalkyl;

R 7 is selected from hydrogen, an optionally substituted C 1 -C 8 aliphatic, an optionally substituted C 1 -C 8 haloaliphatic, an optionally substituted C 1 -C 8 heteroaliphatic, an optionally substituted C 1 -C 8 heterohaloaliphatic, an optionally substituted ring, and (CH 2 ) m R 14 ;

R 8 and R 9 are each independently selected from hydrogen, F, Cl, Br, CO 2 R 10 , NO 2 , CN, SO 2 R 10 , (CH 2 ) m R 14 , C 1 -C 4 aliphatic, C 1 -C 4 haloaliphatic, C 1 -C 4 heteroaliphatic, and C 1 -C 4 heterohaloaliphatic;

R 10 is selected from hydrogen, an optionally substituted C 1 -C 4 aliphatic, C 1 -C 4 haloaliphatic, C 1 -C 4 heteroaliphatic, and a ring;

R 11 is selected from hydrogen, SO 2 R 15 , C 1 -C 4 aliphatic, C 1 -C 4 haloaliphatic, C 1 -C 4 heteroaliphatic, and a ring;

R 12 and R 13 are each independently selected from hydrogen, an optionally substituted C 1 -C 4 aliphatic, an optionally substituted C 1 -C 4 haloaliphatic, an optionally substituted C 1 -C 4 heteroaliphatic, an optionally substituted ring, and (CH 2 ) m R 14 ; or one of R 12 and R 13 is an optionally substituted C 2 -C 6 aliphatic or an optionally substituted ring and the other of R 12 and R 13 is null; or R 12 and R 13 are linked to form an optionally substituted C 3 -C 8 ring;

R 14 is selected from an optionally substituted aryl and an optionally substituted heteroaryl;

R 15 is selected from hydrogen, C 1 -C 3 aliphatic, C 1 -C 3 haloaliphatic, and a ring;

m is 0, 1, or 2; and

n is 0 or 1.

2. A compound of claim 1 wherein:

R 1 is selected from CO 2 R 10 , CONR 10 R 11 , SO 3 R 10 , and a carboxylic acid bioisostere selected from tetrazole, NHSO 2 R 15 , OC(S)NR 10 R 11 , SC(O)NR 10 R 11 , and

wherein A, B, and C are each independently selected from O, S, and N;

R 2 and R 3 are each independently selected from hydrogen, OR 12 , NR 12 R 13 , an optionally substituted C 1 -C 4 alkyl, an optionally substituted C 1 -C 4 haloalkyl, an optionally substituted C 1 -C 4 heteroalkyl, an optionally substituted ring, and (CH 2 ) m R 14 ; or R 2 and R 3 taken together form an optionally substituted olefin; or R 2 and R 3 are linked to form an optionally substituted C 3 -C 8 ring;

R 4 is selected from hydrogen, F, Cl, Br, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, and a non-aromatic ring;

R 7 is selected from hydrogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl, an optionally substituted C 1 -C 8 heteroalkyl, an optionally substituted C 1 -C 8 heterohaloalkyl, an optionally substituted aromatic ring, and (CH 2 ) m R 14 ;

R 8 and R 9 are each independently selected from hydrogen, F, Cl, Br, CO 2 R 10 , NO 2 , CN, SO 2 R 10 , (CH 2 ) m R 4 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, and C 1 -C 4 heterohaloalkyl;

R 10 is selected from hydrogen, an optionally substituted C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl and a non-aromatic ring;

R 11 is selected from hydrogen, SO 2 R 15 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 heteroalkyl, and a non-aromatic ring;

R 12 and R 13 are each independently selected from hydrogen, an optionally substituted C 1 -C 4 alkyl, an optionally substituted C 1 -C 4 haloalkyl, an optionally substituted C 1 -C 4 heteroalkyl, a non-aromatic ring, and (CH 2 ) m R 14 ; or one of R 12 and R 13 is an optionally substituted C 2 -C 6 alkyl or a non-aromatic ring, and the other of R 12 and R 13 is null; or R 12 and R 13 are linked to form an optionally substituted C 3 -C 8 ring; and

R 15 is selected from hydrogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and aryl.

3. The compound of claim 1 selected from:

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-ethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-trifluoromethoxy-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Fluoro-4-methoxy-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-4-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-4-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-ethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-4-carboxylic acid;

3′-{N′-[1-(4-tert-Butyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-trifluoromethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-[N′-(1-Benzyl-5-chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-[N′-(1-Benzyl-5-methyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-[N′-(1-Benzyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-trifluoromethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-4-carboxylic acid;

3′-{N′-[1-(3,4-Dichloro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-methyl-3-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Fluoro-4-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Bis-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(2-Fluoro-4-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(2-Fluoro-4-methyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Chloro-3-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Butyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-m-tolyl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-[N′-(1-Benzyl-5-methoxy-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[5-Chloro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Chloro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Fluoro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Methoxy-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Fluoro-3-trifluoromethyl-phenyl)-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dichloro-phenyl)-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Propyl-phenyl)-6-chloro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid; and

a pharmaceutically acceptable salt, ester, amide, thereof.

4. The compound of claim 1 selected from:

(±)-2′-Hydroxy-3′-(N′-{2-oxo-1-[4-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

(±)-2′-Hydroxy-3′-(N′-{2-oxo-1-[4-(2,2,2-trifluoro-1-methoxy-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-(1′-{2-oxo-1-[4-(2,2,2-trifluoro-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-4,5-dimethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5-fluoro-4-methyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5-fluoro-6-methyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{1-[1-(3,4-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[4-Chloro-1-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Chloro-2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-methylsulfanyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-methoxymethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

(±)-2′-Hydroxy-3′-(N′-{2-oxo-1-[4-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

3′-{N′-[5-Fluoro-1-(4-methyl-3-trifluoromethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-(N′-{2-oxo-1-[4-(2,2,2-trifluoro-1-methoxy-1-methyl-ethyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Fluoro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-5-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Fluoro-2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-propyl-phenyl)-5-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[4,5-Difluoro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-piperidin-4-yl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-{N′-[5-Fluoro-1-(2-fluoro-4-methyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(1-methyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-[N′-(1-Cyclopentyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-methyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-phenyl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-[N′-(6-Fluoro-2-oxo-1-phenyl-2,3-dihydro-1H-indol-3-yl)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-isopropyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-4-isopropyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

5′-Chloro-3′-{N′-[1-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-6-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-4,5-difluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-3-methyl-biphenyl-4-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl]-hydrazino}-2-fluoro-2′-hydroxy-biphenyl-4-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

5′-Chloro-3′-{N′-[1-(3,4-dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3-[(3′-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester;

3-[(3′-Carboxy-4′-fluoro-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester;

3-[(3′-Carboxy-4′-fluoro-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,4-dimethyl-phenyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester;

3-[(3′-Carboxy-5-chloro-4′-fluoro-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester;

3′-{N′-[1-(2-Cyano-thiophen-3-yl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-thiophen-3-yl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3-[(3′-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,4-dimethyl-phenyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester;

3′-{N′-[1-(4-Chloro-3-trifluoromethyl-phenyl)-6-cyano-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

5′-Chloro-3′-{N′-[6-cyano-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Cyano-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-4-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

(±)-1-(3,4-Dimethyl-phenyl)-3-{[2-hydroxy-3′-(2,2,2-trifluoro-1-hydroxy-ethyl)-biphenyl-3-yl]-hydrazono}-6-methanesulfonyl-1,3-dihydro-indol-2-one;

3′-{N′-[6-Cyano-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5-nitro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-methanesulfonyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Cyano-1-(3,4-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(5-Cyano-pyridin-3-yl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-[N′-(1-Furan-3-yl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-[N′-(1-Benzo[1,3]dioxol-5-yl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(3-methyl-thiophen-2-yl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-thiophen-2-yl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-isopropyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-1-(4-propyl-phenyl)-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Ethyl-phenyl)-5,7-difluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5,7-difluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5,7-Difluoro-2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5,7-Difluoro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-ethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-methoxy-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Chloro-1-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6,7-dimethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2-(3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-4-yl)-2-methyl-propionic acid;

(−)-2-(3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-4-yl)-propionic acid;

(+)-2-(3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-4-yl)-propionic acid;

(±)-(3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-5′-methyl-biphenyl-4-yl)-propionic acid;

(±)-2-(3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-5′-fluoro-2′-hydroxy-biphenyl-4-yl)-propionic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-5′-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

5′-Chloro-3′-{N′-[1-(3,4-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[2-oxo-6-trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Ethyl-3-methyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Chloro-3-trifluoromethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-5′-fluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-4,5′-difluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-4,5′-difluoro-2′-hydroxy-biphenyl-3-carboxylic acid;

4,5′-Difluoro-2′-hydroxy-3′-{N′-[2-oxo-6-trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Fluoro-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-methoxy-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Fluoro-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethoxy-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethoxy-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Difluoro-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

5′-Fluoro-3′-{N′-[1-(4-fluoro-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

4,5′-Difluoro-3′-{N′-[1-(4-fluoro-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-methoxy-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-{N′-[1-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Cyclohexyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-pyridin-2-yl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-1-pyridin-3-yl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Ethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Ethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3-[(3′-Carboxy-2-hydroxy-biphenyl-3-yl)-hydrazono]-1-(3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-1-H-indole-5-carboxylic acid methyl ester;

3′-{N′-[1-(3-Chloro-4-methyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-(N′-{2-oxo-1-[4-(4,4,4-trifluoro-butyl)-phenyl]-1,2-dihydro-indol-3-ylidene}-hydrazino)-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-tert-Butyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-4-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-bromo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-3-fluoro-2′-hydroxy-biphenyl-4-carboxylic acid;

3′-{N′-[1-(3,5-Bis-trifluoromethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dichloro-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

2′-Hydroxy-3′-[N′-(2-oxo-7-phenyl-1,2-dihydro-indol-3-ylidene)-hydrazino]-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethoxy-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-(1,1,2,2-tetrafluoro-ethoxy)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-5-methyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Isopropyl-phenyl)-5-methyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-phenyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Trifluoromethyl-phenyl)-6-trifluoromethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethoxy-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Trifluoromethyl-phenyl)-4,6-dimethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Trifluoromethyl-phenyl)-5,6-dimethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-5′-chloro-4-fluoro-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-4-fluoro-biphenyl-3-carboxylic acid;

3′-{N′-[6-Chloro-1-(3,4-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Fluoro-2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[5-Cyano-1-(3,4-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[6-Chloro-1-(3,5-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

4-Fluoro-3′-{N′-[1-(3-fluoro-4-methyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid; and

a pharmaceutically acceptable sale ester, and amide thereof.

5. The compound of claim 1 selected from:

3′-{N′-[1-(4-Chloro-3,5-dimethylphenyl)-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethylphenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-4-fluoro-3-carboxylic acid;

3′-{N′-[1-Benzo[1,3]dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid;

3′-{N′-[1-Benzo[1,3]dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-2-fluoro-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethylphenyl)-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-2-hydroxy-3-carboxylic acid;

3′-{N′-[1-(3-Methoxycarbonylphenyl)-2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid;

3′-{N′-[1-(3-Methoxycarbonylphenyl)-2-oxo-1,2-dihydroindol-3-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid;

3′-{N′-[1-(3,5-Dimethylphenyl)-2-oxo-1,2-dihydroindol-6-trifluoromethyl-3-ylidene]hydrazino}-2′-hydroxybiphenyl-3-(2-methyl-2-propionic acid); and

a pharmaceutically acceptable salt, ester, and amide thereof.

6. A compound of claim 1 that is a selective TPO modulator.

7. A compound of claim 6 that is a TPO mimic.

8. A compound of claim 6 that is a selective TPO receptor agonist.

9. A compound of claim 6 that is a selective TPO receptor partial agonist.

10. A compound of claim 6 that is a selective TPO receptor antagonist.

11. A compound of claim 1 that is a selective TPO receptor binding compound.

12. A method for modulating a TPO activity in a cell comprising contacting a cell with a compound of claim 1 .

13. A method of treating thrombocytopenia in a patient in need thereof with a compound of claim 1 .

14. The method of claim 13 wherein the thrombocytopenia results from radiation or chemotherapy.

15. The method of claim 13 further comprising harvesting cells from the patient.

16. A pharmaceutical composition comprising a physiologically acceptable carrier, diluent, or excipient; and a compound of claim 1 .

17. The pharmaceutical composition of claim 16 for use in treating a condition thrombocytopenia.

18. The compound of claim 1 , wherein:

R 1 is CO 2 R 10 ;

R 2 and R 3 are each null;

R 4 is hydrogen;

R 5 is OR 10 ;

R 6 is hydrogen;

R 7 is phenyl substituted with alkyl;

R 8 is hydrogen, F, Cl, or Br;

R 9 is F, Cl, Br, or C 1 -C 4 haloalkyl;

R 10 is hydrogen; and

n is 0.

19. The compound of claim 18 , selected from 3′-{N′-[6-Chloro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

20. The compound of claim 18 , selected from 3′-{N′-[1-(4-Propyl-phenyl)-6-chloro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

21. The compound of claim 18 , selected from 3′-{N′-[1-(3,4-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifiuoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

22. The compound of claim 18 , selected from 3′-{N′-[1-(3,4-Dimethyl-phenyl)-6-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

23. The compound of claim 18 , selected from 3′-{N′-[6-Fluoro-1-(4-isopropyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

24. The compound of claim 18 , selected from 3′-{N′-[6-Fluoro-2-oxo-1-(4-propyl-phenyl)-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

25. The compound of claim 18 , selected from 2′-Hydroxy-3′-{N′-[1-(4-isopropyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

26. The compound of claim 18 , selected from 2′-Hydroxy-3′-{N′-[2-oxo-1-(4-propyl-phenyl)-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-biphenyl-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.

27. The compound of claim 18 , selected from 3′-{N′-[1-(3,4-Dimethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

28. The compound of claim 18 , selected from 3′-{N-[1-(4-Ethyl-phenyl)-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

29. The compound of claim 18 , selected from 3′-{N′-[1-(4-Ethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

30. The compound of claim 18 , selected from 3-{N′-[1-(3,5-Dimethyl-phenyl)-4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indol-3-ylidene]-hydrazino}-2-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

31. The compound of claim 18 , selected from 3′-{N-[1-(3,5-Dimethyl-phenyl)-6-trifluoromethyl-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

32. The compound of claim 18 , selected from 3′-{N′-[6-Chloro-1-(3,4-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

33. The compound of claim 18 , selected from 3′-{N′-[6-Chloro-1-(3,5-dimethyl-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidene]-hydrazino}-2′-hydroxy-biphenyl-3-carboxylic acid, and a pharmaceutically acceptable salt thereof.

34. The compound of claim 1 wherein:

R is selected from CO 2 R 10 , CONR 10 R 11 , SO 3 R 10 , and a carboxylic acid bioisostere selected from tetrazole, NHSO 2 R 15 , OC(S)NR 10 R 11 , SC(O)NR 10 R 11 , and

wherein A, B, and C are each independently selected from O, S, and N;

R 2 and R 3 are each independently selected from hydrogen, OR 12 , NR 12 R 13 , an optionally substituted C 1 -C 4 alkyl, an optionally substituted C 1 -C 4 haloalkyl, an optionally substituted C 1 -C 4 heteroalkyl, and (CH 2 ) m R 14 ;

R 4 is selected from hydrogen, F, Cl, Br, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 heteroalkyl;

R 5 is selected from OR 10 , SR 10 , NHR 11 , and CO 2 H;

R 7 is selected from hydrogen, an optionally substituted C 1 -C 8 alkyl, an optionally substituted C 1 -C 8 haloalkyl, an optionally substituted C 1 -C 8 heteroalkyl, an optionally substituted C 1 -C 8 heterohaloalkyl, an optionally substituted aromatic ring, and (CH 2 ) m R 14 ;

R 8 and R 9 are each independently selected from hydrogen, F, Cl, Br, CO 2 R 10 , NO 2 , CN, SO 2 R 10 , (CH 2 ) m R 14 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, and C 1 -C 4 heterohaloalkyl;

R 10 is selected from hydrogen, an optionally substituted C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 heteroalkyl;

R 11 is selected from hydrogen, SO 2 R 15 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 heteroalkyl;

R 12 and R 13 are each independently selected from hydrogen, an optionally substituted C 1 -C 4 alkyl, an optionally substituted C 1 -C 4 haloalkyl, an optionally substituted C 1 -C 4 heteroalkyl, and (CH 2 ) m R 14 ; and

R 15 is selected from hydrogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and aryl.

35. The compound of claim 1 , wherein:

R 1 is selected from CO 2 R 10 ;

R 2 and R 3 are each independently selected from null and C 1 -C 4 aliphatic;

R 4 is selected from hydrogen, F, Cl, Br, and C 1 -C 4 aliphatic;

R 5 is OR 10 ;

R 6 is selected from hydrogen, OR 12 , F, Cl, Br, and C 1 -C 4 alkyl;

R 7 is selected from hydrogen, a C 1 -C 8 aliphatic, an optionally substituted ring, and (CH 2 ) m R 14 ;

R 8 and R 9 are each independently selected from hydrogen, F, Cl, Br, CO 2 R 10 , NO 2 , CN, SO 2 R 10 , C 1 -C 4 aliphatic, C 1 -C 4 haloaliphatic, C 1 -C 4 heteroaliphatic, and C 1 -C 4 heterohaloaliphatic;

R 10 is selected from hydrogen and methyl;

R 12 is hydrogen;

R 14 is an optionally substituted aryl;

m is 1; and

n is 0.

36. The compound of claim 35 , wherein:

C 1 -C 4 aliphatic is C 1 -C 4 alkyl;

C 1 -C 4 haloaliphatic is C 1 -C 4 haloalkyl;

C 1 -C 4 heteroaliphatic is C 1 -C 4 heteroalkyl; and

C 1 -C 4 heterohaloaliphatic is C 1 -C 4 heterohaloalkyl.

37. The compound of claim 35 , wherein R 7 is selected from hydrogen, a C 1 -C 8 alkyl, an optionally substituted phenyl, an optionally substituted C 2 -C 5 heterocycle, a C 3 -C 7 alicylic ring, and (CH2) m R 14 , wherein R 14 is phenyl.