Metalloenzyme inhibitor compounds

Abstract

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

1 .- 37 . (canceled) 
     
     
         38 . A method of treating a subject suffering from or susceptible to a metalloenzyme-related disorder or disease, comprising administering to the subject an effective amount of a compound of formula (III) or salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein X is CH, Y is CH, R 2  is alkyl, R 3  is OH, and R 4  and R 5  are independently H, halogen, alkoxy, fluoroalkoxy containing 1-5 fluorines, cyano, carboxamido, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         39 .- 43 . (canceled) 
     
     
         44 . The method of  claim 38 , 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, uterine fibroids, inflammatory bowel disease, psoriasis, systemic fungal infection, onychomycosis, or cardiovascular disease. 
     
     
         45 .- 52 . (canceled) 
     
     
         53 . A composition comprising a compound of formula (III) or salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein X is CH, Y is CH, R 2  is alkyl, R 3  is OH, and 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 a pharmaceutically acceptable carrier. 
     
     
         54 . The composition of  claim 53  further comprising an additional therapeutic agent. 
     
     
         55 . The composition of  claim 53  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. 
     
     
         56 . The composition of  claim 55  wherein the additional therapeutic agent that is an anti-cancer agent. 
     
     
         57 . The composition of  claim 55  wherein the additional therapeutic agent that is breast cancer therapeutic agent. 
     
     
         58 . The composition of  claim 53 , wherein the compound of formula (III) is:
 1-(6,7-Dimethoxynaphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (1);   1-(6,7-Bis(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (3);   2-Methyl-1-(6-(oxazol-5-yl)naphthalen-2-yl)-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (4);   2-methyl-1-(1H-1,2,3-triazol-4-yl)-1-(6-(2,2,2-trifluoroethoxy)naphthalen-2-yl)propan-1-ol (12);   1-(6-(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (13);   or salt thereof.   
     
     
         59 . A method of treating a subject suffering from or susceptible to breast cancer, comprising administering to said subject an effective amount of a compound of formula (III) or salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein X is CH, Y is CH, R 2  is alkyl, R 3  is OH, and R 4  and R 5  are independently H, halogen, alkoxy, fluoroalkoxy containing 1-5 fluorines, cyano, carboxamido, optionally substituted aryl, or optionally substituted heteroaryl. 
     
     
         60 . The method of  claim 59 , said method further comprising administering 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. 
     
     
         61 . The method of  claim 59 , said method further comprising administering an additional therapeutic agent that is an anti-cancer agent. 
     
     
         62 . The method of  claim 59 , said method further comprising administering an additional therapeutic agent that is a breast cancer therapeutic agent. 
     
     
         63 . The method of  claim 59 , wherein the compound of formula (III) is:
 1-(6,7-Dimethoxynaphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (1);   1-(6,7-Bis(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (3);   2-Methyl-1-(6-(oxazol-5-yl)naphthalen-2-yl)-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (4);   2-methyl-1-(1H-1,2,3-triazol-4-yl)-1-(6-(2,2,2-trifluoroethoxy)naphthalen-2-yl)propan-1-ol (12);   1-(6-(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol (13);   or salt thereof.