Biaryl imidazole derivatives for regulating CYP17

1. A compound of formula (I) having the structure:

wherein:

A is optionally substituted phenyl, or pyridine, -2-pyridone, furan, or pyrazole, substituted on the ring carbon atoms with 0 to 2 groups independently selected from CH 3 , CH 3 O, CF 3 , F, Cl, and CN; and substituted on the nitrogen atom in 2-pyridone and pyrazole with H or C 1 to C 4 alkyl;

B is selected from the group consisting of

R 1 is H or optionally substituted C 1 to C 6 alkyl; and

R 2 is optionally substituted C 1 to C 6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein A is of the structure:

wherein:

R 3 , R 4 , R 5 , R 6 and R 7 are, independently, selected from the group consisting of H, halogen, OH, CN, optionally substituted C 1 to C 6 alkyl, C 1 to C 6 alkoxy, amino, (C 1 to C 4 alkyl)—NH—, (C 1 to C 4 alkyl) 2 N—, HC H 2 NC(O)—, (C 1 to C 4 alkyl)-NHC(O)—, (C 1 to C 4 alkyl) 2 NC(O)—, HC(O)NH—, (C 1 to C 4 alkyl)-C(O)NH—, COOH, C 1 to C 6 alkylsulfonyl and —C(O)O(C 1 to C 4 alkyl);

with the proviso that 3, 4 or 5 of R 3 , R 4 , R 5 , R 6 and R 7 are hydrogen.

3. The compound according to claim 2 , wherein R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from H, OH, F, Cl, CN, C 1 to C 4 alkyl, C 1 to C 4 alkoxy, amino, methylamino, dimethylamino, H 2 NC(O)—, CH 3 NHC(O)—, (CH 3 ) 2 NC(O)—, HC(O)NH—, CH 3 C(O)NH—, COOH, methyl-sulfonyl and —C(O)O(C 1 to C 4 alkyl);

with the proviso that 3, 4 or 5 of R 3 , R 4 , R 5 , R 6 and R 7 are hydrogen.

4. The compound according to claim 3 , wherein R 1 is H, or C 1 to C 4 alkyl; and R 2 is C 1 to C 4 alkyl.

5. The compound according to claim 3 , wherein R 1 is H, or C 1 to C 4 alkyl; R 2 is C 1 to C 4 alkyl; and B is

6. The compound according to claim 1 , wherein A is:

7. The compound according to claim 1 , wherein A is 2-pyridone or pyrazole and is substituted on the nitrogen atom with H or C 1 to C 4 alkyl.

8. The compound according to claim 1 , wherein A is:

9. The compound according to claim 1 , wherein:

R 1 is H or C 1 to C 4 alkyl;

R 2 is C 1 to C 4 alkyl; and

B is

10. The compound according to claim 1 , wherein B is

11. The compound according to claim 1 , wherein R 1 is H, or C 1 to C 4 alkyl; and R 2 is C 1 to C 4 alkyl.

12. The compound according to claim 1 , which is:

2-(3-Fluoro-phenyl)-5-(1-imidazol-1-yl-propyl)-thiazole;

5-(1-Imidazol-1-yl-propyl)-2-(1-methyl-1H-pyrazol-4-yl)-thiazole;

1-{1-[5-(4-Methoxy-phenyl)-thiophen-2-yl]-propyl}-1H-imidazole;

4-[5-(1-Imidazol-1-yl-propyl)-thiophen-2-yl]-phenol;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzoic acid ethyl ester;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzoic acid;

2-(1-Imidazol-1-yl-propyl)-5-(3-methoxy-phenyl)-pyridine;

3-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-phenol;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-N-methyl-benzamide;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzamide;

2-(1-Imidazol-1-yl-propyl)-5-(4-methoxymethoxymethyl-phenyl)-pyridine;

5-(4-Fluoro-phenyl)-2-(1-imidazol-1-yl-ethyl)-pyridine;

2-[1-(2,3-Dihydro-imidazol-1-yl)-ethyl]-5-furan-3-yl-pyridine;

4-[6-(1-Imidazol-1-yl-ethyl)-pyridin-3-yl]-phenylamine;

2-(1-Imidazol-1-yl-ethyl)-5-(4-methoxy-phenyl)-pyridine;

4-[6-(1-Imidazol-1-yl-ethyl)-pyridin-3-yl]-phenol;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzonitrile;

2-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzonitrile;

2-(4-Fluoro-phenyl)-5-(1-imidazol-1-yl-propyl)-[1,3,4]thiadiazole;

5-[5-(1-Imidazol-1-yl-ethyl)-thiophen-2-yl]-1-methyl-1H-pyridin-2-one;

5-[5-(1-Imidazol-1-yl-ethyl)-thiophen-2-yl]-1-isopropyl-1H-pyridin-2-one;

4-(5-(1-(1H-imidazol-1-yl)ethyl)thiazol-2-yl)benzonitrile;

4-(5-(1-(1H-imidazol-1-yl)-3-methylbutyl)-thiophen-2-yl)phenol;

1-(2-(5-(4-methoxyphenyl)-thiophen-2-yl)-propan-2-yl)-1H-imidazole;

5-[5-(1-Imidazol-1-yl-ethyl)-thiophen-2-yl]-2-methoxy-pyridine;

4-[5-(1-Imidazol-1-yl-1-methyl-ethyl)-thiophen-2-yl]-phenol;

1-{1-[5-(4-Methoxy-phenyl)-furan-2-yl]-propyl}-1H-imidazole;

2-(2,4-Difluoro-phenyl)-5-(1-imidazol-1-yl-ethyl)-thiazole;

5-(4-Fluoro-phenyl)-2-(1-imidazol-1-yl-propyl)-pyridine;

4-[5-(1-Imidazol-1-yl-propyl)-furan-2-yl]-phenol;

{4-[5-(1-Imidazol-1-yl-propyl)-thiazol-2-yl]-phenyl}-carbamic acid tert-butyl ester;

2-(2,4-Difluoro-phenyl)-5-(1-imidazol-1-yl-propyl)-thiazole;

2-(4-Fluoro-phenyl)-5-(1-imidazol-1-yl-propyl)-thiazole;

5-(4-Fluoro-phenyl)-2-(1-imidazol-1-yl-ethyl)-pyridine;

5-(1-Imidazol-1-yl-propyl)-2-(4-methoxy-phenyl)-thiazole;

1-{1-[5-(4-Methoxy-phenyl)-thiophen-2-yl]-ethyl}-1H-imidazole;

2-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-phenol;

2-(1-Imidazol-1-yl-propyl)-6-(4-methoxy-phenyl)-pyridine

1-{1-[5-(4-Methoxy-phenyl)-thiophen-2-yl]-3-methyl-butyl}-1H-imidazole;

5-(2-Fluoro-phenyl)-2-(1-imidazol-1-yl-ethyl)-pyridine;

{4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-phenyl}-methanol;

2-(1-Imidazol-1-yl-ethyl)-6-(4-methoxy-phenyl)-pyridine;

N-{4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-phenyl}-acetamide;

5-(1-Imidazol-1-yl-propyl)-2-(1H-pyrazol-4-yl)-thiazole;

5-(3-Fluoro-phenyl)-2-(1-imidazol-1-yl-propyl)-pyridine;

2-(2-Ethyl-4-fluoro-phenyl)-5-(1-imidazol-1-yl-propyl)-thiazole;

2-(1-Imidazol-1-yl-propyl)-5-(4-methoxy-phenyl)-pyridine;

5-(2-Fluoro-phenyl)-2-(1-imidazol-1-yl-propyl)-pyridine;

4-[5-(1-Imidazol-1-yl-ethyl)-thiophen-2-yl]-phenol;

4-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-phenol;

5-[5-(1-Imidazol-1-yl-propyl)-thiazol-2-yl]-2-methoxy-pyridine;

4-[6-(1-Imidazol-1-yl-1-methyl-ethyl)-pyridin-3-yl]-phenol;

3-[6-(1-Imidazol-1-yl-propyl)-pyridin-3-yl]-benzonitrile;

2-(4-Fluoro-phenyl)-5-(1-imidazol-1-yl-ethyl)-pyridine;

4-[5-(1-Imidazol-1-yl-ethyl)-thiazol-2-yl]-benzoic acid ethyl ester;

2-(1-Imidazol-1-yl-propyl)-5-(2-methoxy-phenyl)-pyridine;

5-(3-Fluoro-phenyl)-2-(1-imidazol-1-yl-ethyl)-pyridine;

5-[5-(1-Imidazol-1-yl-ethyl)-thiazol-2-yl]-2-methoxy-pyridine;

5-[5-(1-Imidazol-1-yl-propyl)-thiazol-2-yl]-1H-pyridin-2-one;

4-[5-(1-Imidazol-1-yl-propyl)-thiazol-2-yl]-phenol;

2-(1-Imidazol-1-yl-1-methyl-ethyl)-5-(4-methoxy-phenyl)-pyridine;

2-(1-Imidazol-1-yl-3-methyl-butyl)-5-(4-methoxy-phenyl)-pyridine;

5-[5-(1-Imidazol-1-yl-ethyl)-thiazol-2-yl]-1H-pyridin-2-one;

N-{4-[6-(1-Imidazol-1-yl-ethyl)-pyridin-3-yl]-phenyl}-acetamide;

4-[5-(1-Imidazol-1-yl-ethyl)-thiazol-2-yl]-benzoic acid;

4-(5-(1-(1H-imidazol-1-yl)ethyl)thiazol-2-yl)-1H-pyrrole-2-carbonitrile;

4-(5-(1-(1H-imidazol-1-yl)propyl)thiazol-2-yl)-1H-pyrrole-2-carbonitrile;

4-(5-(1-(1H-imidazol-1-yl)ethyl)-1,3,4-thiadiazol-2-yl)-1H-pyrrole-2-carbonitrile;

4-(5-(1-(1H-imidazol-1-yl)propyl)-1,3,4-thiadiazol-2-yl)-1H-pyrrole-2-carbonitrile; or

2-(1-(1H-imidazol-1-yl)ethyl)-3-(4-methoxyphenyl)pyridine.

13. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

14. A kit comprising a compound according to claim 1 .

15. A method for regulating CYP17, said method comprising administering a therapeutically effective amount of a compound of claim 1 to a patient in need thereof.

16. The method according to claim 15 , wherein said regulation comprises inhibition of CYP17 activity.

17. A method of treating prostate cancer in a patient, said method comprising administering a compound of claim 1 to said patient.

18. A method of reducing testosterone production in a patient, comprising administering a compound of claim 1 to said patient.