Metalloenzyme inhibitor compounds

1. A compound of formula (I), or salt, solvate, hydrate or prodrug thereof, wherein:

R 1 is optionally substituted naphthyl;

R 2 is alkyl; and

R 3 is independently optionally H, substituted alkyl, or substituted cycloalkyl.

2. The compound of claim 1 , wherein R 3 is H.

3. The compound of claim 1 , wherein R 2 is lisopropyl, and R 3 is H.

4. The compound of claim 1 , wherein R 1 is substituted naphthyl and R 3 is H.

5. The compound of claim 4 , wherein R 1 is naphthyl substituted with 1, 2, 3 or 4 substituents, independently selected from alkyl, alkoxy, haloalkoxy, cyano, halo, amino, mono-alkylamino, di-alkylamino, or heteroaryl.

6. A compound having the structure of formula (III), or salt, solvate, hydrate, or prodrug thereof:

wherein X is N, Y is CH or N, R 2 is optionally substituted aryl, optionally substituted naphthyl, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl-alkyl or optionally substituted heteroaryl-(di)fluoroalkyl; R 3 is independently optionally H, substituted alkyl, or substituted cycloalkyl; R 4 and R 5 are independently H, halogen, alkoxy, fluoroalkoxy containing 1-5 fluorines, cyano, carboxamido, optionally substituted aryl, or optionally substituted heteroaryl; and R 6 is independently H, halogen, alkoxy, aryloxy, thioalkoxy, cycloalkoxy, haloalkoxy, fluoroalkoxy containing 1-5 fluorines, cyano, carboxamido, optionally substituted aryl, or optionally substituted heteroaryl.

7. The compound of claim 6 , wherein Y═N.

8. The compound of claim 6 , wherein Y═CH.

9. The compound of claim 1 that is:

1-(1-(6,7-dimethoxynaphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (1);

1-(1-(6,7-bis(2,2,2-trifluoroethoxy)naphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (2);

1-(2-methyl-1-(6-(2,2,2-trifluoroethoxy)naphthalen-2-yl)propyl)-1H-1,2,3-triazole (5);

1-(1-(6-isopropoxynaphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (6);

1-(1-(6-methoxynaphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (7);

1-(1-(6-ethoxynaphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (8);

1-(1-(6,7-bis(difluoromethoxy)naphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (9);

1-(1-(6-(difluoromethoxy)naphthalen-2-yl)-2-methylpropyl)-1H-1,2,3-triazole (10);

6-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-2-naphthonitrile (12);

or salt, solvate, hydrate or prodrug thereof.

10. A method of treating a subject suffering from a metalloenzyme-related disorder or disease, comprising administering to the subject an effective amount of a compound of claim 1 or 6 ;

wherein the metalloenzyme-related disorder or disease is mediated by 17-alpha hydroxylase (CYP17).

11. The method of claim 10 , wherein the disease or disorder is prostate cancer, breast cancer, androgen-dependent cancers, estrogen-dependent cancers, adrenal hyperplasia, prostatic hypertrophy, virilism, hirsutism, male pattern alopecia, precocious puberty, endometriosis, uterus myoma, uterine cancer, mastopathy, polycystic ovary syndrome, infertility, acne, functional ovarian hyperandrogenism, hyperandrogenism with chronic anovulation, hyperandrogenemia, premature adrenarche, adrenal or androgen excess, or uterine fibroids.

12. A composition comprising a compound of claim 1 or 6 and a pharmaceutically acceptable carrier.

13. The composition of claim 12 further comprising an additional therapeutic agent.

14. The composition of claim 12 further comprising an additional therapeutic agent that is an anti-cancer agent, antifungal agent, cardiovascular agent, antiinflammatory agent, chemotherapeutic agent, an anti-angiogenesis agent, cytotoxic agent, an anti-proliferation agent, metabolic disease agent, opthalmologic disease agent, central nervous system (CNS) disease agent, urologic disease agent, or gastrointestinal disease agent.

15. The compound of claim 6 that is:

2-(2-Methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-6-(2,2,2-trifluoroethoxy)quinoline (3);

6-(4-Fluorophenyl)-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (4);

6-methoxy-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (11);

6-(difluoromethoxy)-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (13);

6,7-dichloro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (14);

2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-6-(trifluoromethoxy)quinoline (15);

6,7-difluoro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (16);

5-fluoro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-6-(thiophen-2-yl)quinoline (17);

5-chloro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-6-(2,2,2-trifluoroethoxy)quinoline (18);

6,7-bis(difluoromethoxy)-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (19);

5-chloro-6-(difluoromethoxy)-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (20);

5,6-dichloro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline (21);

5-chloro-2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)-6-(trifluoromethoxy)quinoline (22);

2-(2-methyl-1-(1H-1,2,3-triazol-1-yl)propyl)quinoline-6-carbonitrile (23);

or salt, solvate, hydrate or prodrug thereof.

16. The compound of claim 8 , wherein R 2 is alkyl and R 3 is H.

17. The compound of claim 16 , wherein R 2 is isopropyl.