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; and 
         the disease or disorder is cardiovascular disease, inflammatory disease, infectious disease, metabolic disease, ophthalmologic disease, central nervous system (CNS) disease, urologic disease, or gastrointestinal disease. 
       
     
     
         39 .- 43 . (canceled) 
     
     
         44 . 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; and 
         wherein the disease or disorder is 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 method of  claim 38 , 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. 
     
     
         57 . The method of  claim 44 , 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. 
     
     
         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 . The composition of  claim 58  further comprising an additional therapeutic agent. 
     
     
         60 . The composition of  claim 58  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. 
     
     
         61 . A composition comprising a compound that 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 and a pharmaceutically acceptable carrier. 
     
     
         62 . The composition of  claim 61  further comprising an additional therapeutic agent. 
     
     
         63 . The composition of  claim 61  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.