Large conductance calcium-activated k channel opener

Abstract

A large conductance calcium-activated K channel opener comprising as an active ingredient a nitrogen-containing 5-membered heterocyclic compound represented by the following formula (I): wherein X represents N—R 4 , O or S, R 1 and R 2 each independently represent hydrogen, halogen, carboxyl, amino, lower alkyl, lower alkoxycarbonyl, lower alkenyl, cyclo-lower alkyl, carbamoyl, aryl, heterocyclic or heterocyclic-substituted carbonyl group, R 3 represents aryl, heterocyclic or lower alkyl group, and R 4 represents hydrogen or lower alkyl group, or a pharmaceutically acceptable salt thereof.

1 . A nitrogen-containing 5-membered heterocyclic compound represented by the following formula (I): 
       
         
           
           
               
               
           
         
       
       wherein X is S or O;
 R 1  is a heterocyclic group which is substituted by at least one group selected from nitro group, hydroxyl group, formyl group, carbamoyl group, cyano group, amino group, carboxyl group, a lower alkoxycarbonyl group, a halogen atom, a lower alkyl group, a hydroxy-lower alkyl group, a lower alkoxy group, a mono- or di-lower alkylamino group, a mono- or di-lower alkanoylamino group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkylsulfinyl group, sulfamoyl group and a mono- or di-lower alkylsulfamoyl group, where the heterocyclic group is a monocyclic, dicyclic or tricyclic 6- to 14-membered aromatic hydrocarbon cyclic group, containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, which may be partially or wholly saturated; 
 R 2  is a lower alkyl group which may be substituted by at least one group selected from a carboxyl group and a lower alkoxycarbonyl; and 
 R 3  is (1) an aryl group which may be substituted by at least one group selected from cyano group, nitro group, amino group, a halogen atom, trifluoromethyl group, carboxyl group, hydroxyl group, carbamoyl group, a mono- or di-lower alkylamino group, a mono- or di-lower alkylamino-lower alkyl group, a mono- or di-lower alkylcarbamoyl group, a lower alkyl group, a hydroxy-lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkanoyloxy-lower alkyl group, sulfo group, a lower alkylthio group, a lower alkylthio-lower alkyl group, a lower alkylsulfonyl group, a lower alkylsulfamoyl group and a lower alkylsulfinyl group, where the aryl of R 1 , R 2  or R 3  is a monocyclic, dicyclic or tricyclic 6- to 14-membered aromatic hydrocarbon cyclic group, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A nitrogen-containing 5-membered heterocyclic compound according to  claim 1 , 
       wherein
 R 1  is a thienyl group which is substituted by at least one group selected from a halogen atom and a lower alkyl group; 
 R 2  is a carboxymethyl group; and 
 R 3  is a phenyl group which is substituted by at least one group selected from a halogen atom and a lower alkoxy group, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . A pharmaceutical composition comprising a therapeutically effective amount of a compound as set forth in  claim 1  or  2  or a pharmaceutically acceptable salt thereof in admixture with a therapeutically acceptable carrier or diluent.