Therapeutic agent for cerebral infarction

Abstract

The present invention provides a novel therapeutic drug for cerebral infarction, which contains a piperazine compound as an active ingredient. The compound of the present invention can be provided as a novel therapeutic drug for cerebral infarction having an effect of suppressing brain injury volume or improving neurological deficit, since it suppresses production of plural inflammatory cytokines and chemokines present in the brain such as TNF-α, IL-1β, IL-6 and MCP-1 and the like.

1 . A piperazine compound represented by the formula <2> 
       
         
           
           
               
               
           
         
         wherein
 R 1  and R 2  are the same or different and each is hydrogen, halogen, lower alkyl, lower alkoxy, amino, amino which is mono- or di-substituted by group(s) selected from lower alkyl and lower acyl, nitro, hydroxy or cyano, 
 R 3 , R 4  and R 5  are the same or different and each is amino, hydroxy or cyano, which is mono- or di-substituted by group(s) selected from hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, lower alkyl and lower acyl, 
 R 6  and R 7  are the same or different and each is hydrogen, lower alkyl, lower alkyl substituted by 1 to 3 halogens, aralkyl, acyl or lower acyl substituted by 1 to 3 halogens, 
 R 8  and R 9  are the same or different and each is hydrogen or lower alkyl, 
 R a -R d  are the same or different and each is hydrogen, lower alkyl, aralkyl or hydroxy lower alkyl, or any two of R a -R d  are bonded to each other to form alkylene having a carbon number of 1-2, 
 Y is a group represented by the formula 
 
       
       
         
           
           
               
               
           
         
         wherein
 R 10  and R 11  are the same or different and each is hydrogen or lower alkyl, 
 R 12  and R 13  are the same or different and each is hydrogen or lower alkyl, or R 12  and R 13  are groups that form alkylene in combination, 
 R 14  and R 15  are the same or different and each is hydrogen or lower alkyl, 
 m is an integer of 0-2, n is an integer of 0-2, and 0≦m+n≦2, 
 ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyradyl or imidazolyl, and 
 ring B 1  is pyridyl or thienyl, 
 
         or a pharmaceutically acceptable salt thereof.