Compounds for modulating trpv3 function

Abstract

The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.

1 - 38 . (canceled) 
     
     
         39 . A method for treating allergies in a subject, the method comprising administering to the subject a compound of formula I or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 m represents 0, 1, 2, 3, or 4; and 
 R 5  represents a substituent on the ring to which it is attached. 
 
     
     
         40 . The method of  claim 39 , wherein each of R 1 , R 2 , R 3  and R 4  represent H, lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , aryl, —CH 2 CH═CF 2 , —CH═CF 2 , or cyano. 
     
     
         41 . The method of  claim 39 , wherein R 5  is, independently for each occurrence, selected from lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , and cyano. 
     
     
         42 . The method of  claim 39 , wherein X is S; R 1  represents H; R 2 , R 3  and R 4  represent H, lower alkyl, halogen, or CF 3 ; and m is 0. 
     
     
         43 . The method of  claim 39 , wherein the compound of formula I is a compound of formula Ib or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3  and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 y represents 0, 1, 2, or 3; 
 R 5  represents a substituent on the ring to which it is attached; 
 R 5 ′ represents a substituent. 
 
     
     
         44 . The method of  claim 39 , wherein the compound of formula I is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         45 . A method for treating a gastrointestinal disease in a subject, the method comprising administering to the subject a compound of formula I or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 m represents 0, 1, 2, 3, or 4; and 
 R 5  represents a substituent on the ring to which it is attached. 
 
     
     
         46 . The method of  claim 45 , wherein the gastrointestinal disease Crohn's disease, ulcerative colitis, irritable bowel syndrome, celic sprue, or dermatitis herpetiformis. 
     
     
         47 . The method of  claim 45 , wherein each of R 1 , R 2 , R 3  and R 4  represent H, lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , aryl, —CH 2 CH═CF 2 , —CH═CF 2 , or cyano. 
     
     
         48 . The method of  claim 45 , wherein R 5  is, independently for each occurrence, selected from lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , and cyano. 
     
     
         49 . The method of  claim 45 , wherein X is S; R 1  represents H; R 2 , R 3  and R 4  represent H, lower alkyl, halogen, or CF 3 ; and m is 0. 
     
     
         50 . The method of  claim 45 , wherein the compound of formula I is a compound of formula Ib or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3  and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 y represents 0, 1, 2, or 3; 
 R 5  represents a substituent on the ring to which it is attached; 
 R 5 ′ represents a substituent. 
 
     
     
         51 . The method of  claim 45 , wherein the compound of formula I is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         52 . A method for treating an inflammatory disease or disorder in a subject, the method comprising administering to the subject a compound of formula I or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 m represents 0, 1, 2, 3, or 4; and 
 R 5  represents a substituent on the ring to which it is attached. 
 
     
     
         53 . The method of  claim 52 , wherein the inflammatory disease or disorder is asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, glomerulonephritis, or multiple sclerosis. 
     
     
         54 . The method of  claim 52 , wherein each of R 1 , R 2 , R 3  and R 4  represent H, lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , aryl, —CH 2 CH═CF 2 , —CH═CF 2 , or cyano. 
     
     
         55 . The method of  claim 52 , wherein R 5  is, independently for each occurrence, selected from lower alkyl, alkoxy, carboxyl, ester, amido, sulfonamido, heterocyclyl, cycloalkyl, hydroxyl, amino, acylamino, thioether, sulfonylamino, nitro, halogen, CF 3 , and cyano. 
     
     
         56 . The method of  claim 52 , wherein X is S; R 1  represents H; R 2 , R 3  and R 4  represent H, lower alkyl, halogen, or CF 3 ; and m is 0. 
     
     
         57 . The method of  claim 52 , wherein the compound of formula I is a compound of formula Ib or a pharmaceutically acceptable salt, solvate, hydrate, oxidative metabolite, or prodrug thereof 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3  and R 4  represent H or a substituent; 
 X represents S or O; 
 n represents 1 or 2 when X is O, or n represents 1 when X is S; 
 y represents 0, 1, 2, or 3; 
 R 5  represents a substituent on the ring to which it is attached; 
 R 5 ′ represents a substituent. 
 
     
     
         58 . The method of  claim 52 , wherein the compound of formula I is