Xanthine oxidase inhibitor

Abstract

Provided are a xanthine oxidase inhibitor, a drug for improving vascular endothelial function, and an excellent therapeutic or prophylactic drug for diseases associated with xanthine oxidase such as gout, hyperuricaemia, and for diseases associated with vascular endothelial functional disorder containing a compound represented in a formula (I) or the pharmaceutically acceptable salt thereof as an active ingredient.

1 . A xanthine oxidase inhibitor comprising a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: 
       
         
           
           
               
               
           
         
         [wherein,
 R 1  represents OR, NRR′ which may form a ring or SR, in which R and R′ independently represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms optionally substituted with one or a plurality of alkoxy groups having 1 to 8 carbon atoms, halogen atoms or hydroxyl groups, or an aryl group optionally substituted with one or a plurality of alkyl groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms or halogen atoms, or a heteroaryl group optionally substituted with one or a plurality of alkyl groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms or halogen atoms, 
 R 2  represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, 
 X 1 , X 2  and X 3  are independently CR 3  or a nitrogen atom, or X 1  is CR 3  or a nitrogen atom, and X 2  and X 3  together form a benzene ring, in which R 3  is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms.] 
 
       
     
     
         2 . A therapeutic agent or a prophylactic agent for diseases associated with xanthine oxidase, which contains a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. 
     
     
         3 . The therapeutic agent or the prophylactic agent according to  claim 2 , wherein the disease is gout, hyperuricemia or tumor lysis syndrome or kidney disease. 
     
     
         4 . An agent for improving vascular endothelial function containing a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. 
     
     
         5 . A therapeutic agent or a prophylactic agent for diseases associated with vascular endothelial function disorder containing a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. 
     
     
         6 . The therapeutic agent or the prophylactic agent according to  claim 5 , wherein the disease is arteriosclerosis, myocardial infarction, cerebral infarction or cerebrovascular dementia. 
     
     
         7 . The agent according to  claim 1 , wherein R 1  is OR. 
     
     
         8 . The agent according to  claim 1 , wherein R 1  is SR. 
     
     
         9 . The agent according to, wherein R 1  is NRR′ which may form a ring. 
     
     
         10 . The agent according to  claim 1 , wherein R and R′ are independently an alkyl group having 1 to 8 carbon atoms optionally substituted with one or a plurality of alkoxy groups having 1 to 8 carbon atoms, halogen atoms or hydroxyl groups, or an aryl group optionally substituted with one or a plurality of alkyl groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms or halogen atoms. 
     
     
         11 . The agent according to  claim 10 , wherein R and R′ are independently an alkyl group having 1 to 8 carbon atoms optionally substituted with one or a plurality of alkoxy groups having 1 to 8 carbon atoms, halogen atoms or hydroxyl groups. 
     
     
         12 . The agent according to  claim 11 , wherein R 1  is OR or SR, and R is an isopropyl group, a isobutyl group or a neopentyl group. 
     
     
         13 . The agent according to  claim 1 , wherein R 2  is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. 
     
     
         14 . The agent according to  claim 13 , wherein R 2  is a methyl group. 
     
     
         15 . The agent according to  claim 1 , wherein X 1 , X 2  and X 3  are independently CR 3  or a nitrogen atom. 
     
     
         16 . The agent according to  claim 15 , wherein X 1  is a nitrogen atom, X 2  is CR 3  or a nitrogen atom and X 3  is CR 3 . 
     
     
         17 . The agent according to  claim 1 , wherein R 3  is a hydrogen atom. 
     
     
         18 . The agent according to  claim 1 , wherein a compound represented by the formula (I) is
 4-methyl-2-[4-(2-methylpropoxy)-3-(1H-1,2,3-triazol-1-yl)phenyl]-1,3-thiazole-5-carboxylic acid,   4-methyl-2-[4-(2-methylpropoxy)-3-(1H-1,2,3,4-tetrazol-1-yl)phenyl]-1,3-thiazole-5-carboxylic acid or   2-[4-(2,2-dimethylpropoxy)-3-(1H-1,2,3,4-tetrazol-1-yl)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid.