Acetic acid amide derivative having inhibitory activity on endothelial lipase

Abstract

A pharmaceutical composition including a compound of formula (I): its pharmaceutically acceptable salt, or a solvate thereof. Ring A is nitrogen-containing hetero ring, Ring A may be substituted with a substituent other than a group represented by formula: —C(R 1 R 2 )—C(═O)—NR 3 R 4 and a group represented by formula: —R 5 , a broken line represents presence or absence of a bond, Z is —NR 6 —, ═N—, —O—, or —S—, R 6 is halogen or substituted or unsubstituted alkyl, R 1 and R 2 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy or substituted or unsubstituted alkyl, R 3 is hydrogen or substituted or unsubstituted alkyl, R 4 is hydrogen or substituted or unsubstituted alkyl, R 3 and R 4 taken together with the adjacent nitrogen atom to which they are attached may form a substituted or unsubstituted ring, R 5 is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

1 . A pharmaceutical composition comprising:
 a compound represented by formula (I):   
       
         
           
           
               
               
           
         
         its pharmaceutically acceptable salt, or a solvate thereof, 
         wherein the pharmaceutical composition has inhibitory activity on endothelial lipase, 
         Ring A is nitrogen-containing hetero ring, 
         Ring A may be substituted with a substituent other than a group represented by the formula: —C(R 1 R 2 )—C(═O)—NR 3 R 4  and a group represented by the formula: —R 5 , 
         a broken line represents the presence or the absence of a bond, 
         Z is —NR 6 —, ═N—, —O—, or —S—, 
         R 6  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 or substituted or unsubstituted heterocycle, 
         R 1  and R 2  are each independently hydrogen, halogen, cyano, nitro, carboxy or substituted or unsubstituted alkyl, 
         R 3  is hydrogen or substituted or unsubstituted alkyl, 
         R 4  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 heterocycle or substituted or unsubstituted amino, 
         R 3  and R 4  taken together with the adjacent nitrogen atom to which they are attached may form a substituted or unsubstituted ring, 
         R 5  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 heterocycle, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocycleoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclethio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclesulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl or substituted or unsubstituted amino, 
         with the proviso that compounds wherein Ring A is thiazolopyrimidine and R 3  and R 4  taken together with the adjacent nitrogen atom to which they are attached may form a substituted or unsubstituted ring are excluded. 
       
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein Z is —S—. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein Ring A is monocyclic nitrogen-containing aromatic hetero ring. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein Ring A is bicyclic nitrogen-containing aromatic hetero ring. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocycleoxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclethio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclesulfonyl or substituted or unsubstituted amino. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl or substituted or unsubstituted amino. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein R 4  is substituted or unsubstituted alkyl, wherein substituted or unsubstituted alkyl is substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl. 
     
     
         8 . The pharmaceutical composition according to  claim 2 , wherein Ring A is monocyclic nitrogen-containing aromatic hetero ring. 
     
     
         9 . The pharmaceutical composition according to  claim 2 , wherein Ring A is bicyclic nitrogen-containing aromatic hetero ring. 
     
     
         10 . The pharmaceutical composition according to  claim 2 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocycleoxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclethio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclesulfonyl or substituted or unsubstituted amino. 
     
     
         11 . The pharmaceutical composition according to  claim 3 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocycleoxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclethio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclesulfonyl or substituted or unsubstituted amino. 
     
     
         12 . The pharmaceutical composition according to  claim 4 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocycleoxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclethio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclesulfonyl or substituted or unsubstituted amino. 
     
     
         13 . The pharmaceutical composition according to  claim 2 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl or substituted or unsubstituted amino. 
     
     
         14 . The pharmaceutical composition according to  claim 3 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl or substituted or unsubstituted amino. 
     
     
         15 . The pharmaceutical composition according to  claim 4 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl or substituted or unsubstituted amino. 
     
     
         16 . The pharmaceutical composition according to  claim 5 , wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl or substituted or unsubstituted amino. 
     
     
         17 . The pharmaceutical composition according to  claim 2 , wherein R 4  is substituted or unsubstituted alkyl, wherein substituted or unsubstituted alkyl is substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl. 
     
     
         18 . The pharmaceutical composition according to  claim 3 , wherein R 4  is substituted or unsubstituted alkyl, wherein substituted or unsubstituted alkyl is substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl. 
     
     
         19 . The pharmaceutical composition according to  claim 4 , wherein R 4  is substituted or unsubstituted alkyl, wherein substituted or unsubstituted alkyl is substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl. 
     
     
         20 . The pharmaceutical composition according to  claim 5 , wherein R 4  is substituted or unsubstituted alkyl, wherein substituted or unsubstituted alkyl is substituted or unsubstituted arylalkyl or substituted or unsubstituted heteroarylalkyl.