Metalloenzyme inhibitor compounds as fungicides

Abstract

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

1 - 18 . (canceled) 
     
     
         19 . A method of treating a subject suffering from or susceptible to a metalloenzyme-related disorder or disease, wherein the subject has been identified as in need of treatment for a metalloenzyme-related disorder or disease, comprising administering to said subject in need thereof, an effective amount of a compound of Formula I, or salt thereof, wherein: 
       
         
           
           
               
               
           
         
         Z is optionally substituted 5-pyrimidinyl, optionally substituted 4-pyrimidinyb optionally substituted thiazolyl, optionally substituted oxazolyl, or optionally substituted 3-pyridinyl; 
         R 1  is alkyl, haloalkyl, aryl, or heteroaryl, each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 2  is aryl or heteroaryl each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 3  is independently H, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, —C(O)alkyl, or —Si(alkyl) 3 , each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 4 , R 5 , R 6 , and R 7  are independently H, alkyl, haloalkyl, alkoxy, halo, or cyano; and 
         R 8  is independently aryl, heteroaryl, alkyl, thioalkyl, cyano, haloalkyl, cyanoalkyl, hydroxy, alkoxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)O-alkyl, —SCF 3 , —SF 5 , —SCN, or —SO 2 - alkyl, such that said subject is treated for said disorder. 
       
     
     
         20 . A method of treating a subject suffering from or susceptible to a metalloenzyme-mediated disorder or disease, wherein the subject has been identified as in need of treatment for a metalloenzyme-mediated disorder or disease, comprising administering to said subject in need thereof, an effective amount of a compound of Formula I, or salt thereof wherein: 
       
         
           
           
               
               
           
         
         Z is optionally substituted 5-pyrimidinyl, optionally substituted 4-pyrimidinyl, optionally substituted thiazolyl, optionally substituted oxazolyl, or optionally substituted 3-pyridinyl; 
         R 1  is alkyl, haloalkyl, aryl, or heteroaryl, each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 2  is aryl or heteroaryl each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 3  is independently H, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, —C(O)alkyl, or —Si(alkyl) 3 , each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 4 , R 5 , R 6 , and R 7  are independently H, alkyl, haloalkyl, alkoxy, halo, or cyano; and 
         R 8  is independently aryl, heteroaryl, alkyl, thioalkyl, cyano, haloalkyl, cyanoalkyl, hydroxy, alkoxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)O-alkyl, —SCF 3 , —SF 5 , —SCN, or —SO 2 -alkyl, such that metalloenzyme activity in said subject is modulated (e.g., down regulated, inhibited). 
       
     
     
         21 . The method according to  claim 20 , wherein the disease or disorder is cancer, cardiovascular disease, endocrinologic disease, inflammatory disease, infectious disease, gynecologic disease, metabolic disease, opthalmologic disease, central nervous system (CNS) disease, urologic disease, or gastrointestinal disease. 
     
     
         22 . The method according to  claim 20 , wherein the disease or disorder is systemic fungal infection, mucosal infection, or dermal infection. 
     
     
         23 - 32 . (canceled) 
     
     
         33 . A composition comprising a compound of Formula I, or salt thereof wherein: 
       
         
           
           
               
               
           
         
         Z is optionally substituted 5-pyrimidinyl, optionally substituted 4-pyrimidinyl, optionally substituted thiazolyl, optionally substituted oxazolyl, or optionally substituted 3-pyridinyl; 
         R 1  is alkyl, haloalkyl, aryl, or heteroaryl, each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 2  is aryl or heteroaryl each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 3  is independently H, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, —C(O)alkyl, or —Si(alkyl) 3 , each optionally substituted with 0, 1, 2 or 3 independent R 8 ; 
         R 4 , R 5 , R 6 , and R 7  are independently H, alkyl, haloalkyl, alkoxy, halo, or cyano; and 
         R 8  is independently aryl, heteroaryl, alkyl, thioalkyl, cyano, haloalkyl, cyanoalkyl, hydroxy, alkoxy, halo, haloalkoxy, —C(O)alkyl, —C(O)OH, —C(O)O-alkyl, —SCF 3 , —SF 5 , —SCN, or —SO 2 -alkyl, and 
         a pharmaceutically acceptable carrier. 
       
     
     
         34 . The composition according to  claim 33 , further comprising an additional therapeutic agent. 
     
     
         35 . The composition according to  claim 33 , 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. 
     
     
         36 - 39 . (canceled)