Oxadiazole derivative having endothelial lipase inhibitory activity

Abstract

A compound represented by formula: its pharmaceutically acceptable salt, or a solvate thereof. Ring B is substituted or unsubstituted nitrogen-containing hetero ring, R 2 and R 3 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy, R 2 and R 3 taken together may form oxo, R 4 is a group represented by the formula: —(CR 6 R 7 )n—R 8 , R 6 and R 7 are each independently hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy, R 6 and R 7 taken together with the adjacent carbon atom to which they are attached may form a substituted or unsubstituted ring, and n is an integer of 0 to 3.

1 . A compound represented by formula (III): 
       
         
           
           
               
               
           
         
         its pharmaceutically acceptable salt, or a solvate thereof, 
         wherein 
         Ring B is a group represented by the formula: 
       
       
         
           
           
               
               
           
         
         wherein 
         Ring A is aromatic carbocycle, non-aromatic carbocycle, aromatic heterocycle or non-aromatic heterocycle, 
         Z is —NR 5 —, —O— or —S—, 
         R 5  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyloxycarbonyl or substituted or unsubstituted acyl, 
         R 1  is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocyclyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclylthio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl or substituted or unsubstituted amino, 
         R x  is halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocyclyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclylthio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl or substituted or unsubstituted amino, 
         m is an integer of 0 to 3, 
         R 1a  and R 1b  are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocyclyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclylthio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl or substituted or unsubstituted amino, 
         R 1a  and R 1b  taken together with the adjacent carbon atom to which they are attached may form a substituted or unsubstituted ring, 
         Z 1  is ═CR 1 — or ═N—, 
         Z 2  is —CR 1 ═ or —N═, 
         R 2  and R 3  are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy, 
         R 2  and R 3  taken together may form oxo, 
         R 4  is a group represented by the formula: —(CR 6 R 7 )n-R 8 , 
         wherein R 6  and R 7  are each independently hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted alkyl or substituted or unsubstituted alkyloxy, R 6  and R 7  taken together with the adjacent carbon atom to which they are attached may form a substituted or unsubstituted ring, n is an integer of 0 to 3, R 8  is carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, with the proviso that n is not 0 when R 8  is substituted or unsubstituted acyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyloxy or substituted or unsubstituted alkyloxy, 
         with the proviso that the compounds wherein Ring B is substituted or unsubstituted benzimidazole, n is 0 and R 8  is substituted or unsubstituted amino and the compound shown as follows are excluded: 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, wherein R 1a  and R 1b  taken together with the adjacent carbon atom to which they are attached form a substituted or unsubstituted ring. 
     
     
         3 . A pharmaceutical composition comprising the compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof. 
     
     
         4 . A pharmaceutical composition comprising the compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, which has an inhibitory activity on endothelial lipase. 
     
     
         5 . The compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Z is —O— or —S—. 
     
     
         6 . The compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic carbocycle or non-aromatic heterocycle. 
     
     
         7 . The compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic carbocycle. 
     
     
         8 . The compound according to  claim 1 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic heterocycle. 
     
     
         9 . The compound according to  claim 5 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic carbocycle or non-aromatic heterocycle. 
     
     
         10 . The compound according to  claim 5 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic carbocycle. 
     
     
         11 . The compound according to  claim 5 , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is non-aromatic heterocycle. 
     
     
         12 . The pharmaceutical composition according to  claim 3 , wherein Z is —O— or —S—. 
     
     
         13 . The pharmaceutical composition according to  claim 3 , wherein Ring A is non-aromatic carbocycle or non-aromatic heterocycle. 
     
     
         14 . The pharmaceutical composition according to  claim 3 , wherein Ring A is non-aromatic carbocycle. 
     
     
         15 . The pharmaceutical composition according to  claim 3 , wherein Ring A is non-aromatic heterocycle. 
     
     
         16 . The pharmaceutical composition according to  claim 4 , wherein Z is —O— or —S—. 
     
     
         17 . The pharmaceutical composition according to  claim 4 , wherein Ring A is non-aromatic carbocycle or non-aromatic heterocycle. 
     
     
         18 . The pharmaceutical composition according to  claim 4 , wherein Ring A is non-aromatic carbocycle. 
     
     
         19 . The pharmaceutical composition according to  claim 4 , wherein Ring A is non-aromatic heterocycle.