Method of inhibiting xanthine oxidase activity in a cell

Abstract

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia.

1 - 15 . (canceled) 
     
     
         16 . A method for treating gout or hyperuricemia in a subject, comprising:
 administering to the subject a therapeutically effective amount of a compound of the formula:   
       
         
           
           
               
               
           
         
          or a pharmaceutically acceptable salt thereof, wherein: 
         R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from hydrogen, hydroxyl, cyano, fluoro, chloro, bromo, trifluoromethyl, sulfonyl, and aldehyde; 
         wherein R 1 , R 2 , R 3 , R 4 , and R 5  are not simultaneously hydrogen; and 
         wherein n is 1 or 2. 
       
     
     
         17 . The method of  claim 16 , further comprising administering a second therapeutic agent to the subject. 
     
     
         18 . The method of  claim 17 , wherein the second therapeutic agent is an anti-gout agent. 
     
     
         19 . The method of  claim 18 , wherein the anti-gout agent is selected from the group consisting of allopurinol, benzbromarone, colchicine, probenecid, and sulfinpyrazone. 
     
     
         20 . The method of  claim 17 , wherein the second therapeutic agent is an anti-inflammatory agent. 
     
     
         21 . The method of  claim 17 , wherein the second therapeutic agent is an antioxidant. 
     
     
         22 . The method of  claim 16 , wherein the compound is administered orally. 
     
     
         23 . A method for reducing uric acid production in a subject, comprising:
 administering to the subject a therapeutically effective amount of a compound of the formula:   
       
         
           
           
               
               
           
         
          or a pharmaceutically acceptable salt thereof, wherein: 
         R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from hydrogen, hydroxyl, cyano, fluoro, chloro, bromo, trifluoromethyl, sulfonyl, and aldehyde; 
         wherein R 1 , R 2 , R 3 , R 4 , and R 5  are not simultaneously hydrogen; and 
         wherein n is 1 or 2. 
       
     
     
         24 . The method of  claim 23 , wherein the compound is administered orally. 
     
     
         25 . The method of  claim 23  wherein the method further comprises selecting a subject having gout or hyperuricemia. 
     
     
         26 . A method for reducing reactive oxygen species production in a subject, comprising:
 administering to the subject a therapeutically effective amount of a compound of the formula:   
       
         
           
           
               
               
           
         
          or a pharmaceutically acceptable salt thereof, wherein: 
         R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from hydrogen, hydroxyl, cyano, fluoro, chloro, bromo, trifluoromethyl, sulfonyl, and aldehyde; 
         wherein R 1 , R 2 , R 3 , R 4 , and R 5  are not simultaneously hydrogen; and 
         wherein. n is 1 or 2. 
       
     
     
         27 . The method of  claim 25 , wherein the compound is administered orally. 
     
     
         28 . A method of inhibiting xanthine oxidase activity in a cell, comprising: contacting a cell with an effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently selected from hydrogen, hydroxyl, cyano, fluoro, chloro, bromo, trifluoromethyl, sulfonyl, and aldehyde; 
 wherein R 1 , R 2 , R 3 , R 4 , and R 5  are not simultaneously hydrogen; and 
 wherein. n is 1 or 2. 
 
     
     
         29 . The method of  claim 25 , wherein the compound is administered orally. 
     
     
         30 . A method for treating a condition mediated at least in part by xanthine oxidase, wherein the method comprises administering to a patient suffering from such a condition a therapeutically effective amount of a compound of  claim 28 .