Compound for treating sequelae of ischemic cerebral stroke

Abstract

The present invention provides a compound (I) for treating sequelae of ischemic cerebral stroke: H—(NH—CHR 1 —CO)—(NH—CHR 2 —CO)—(NH—CHR 3 —CO)—(NH—CHR 4 —CO)—(NH—CHR 5 —CO)—(NH—CHR 6 —CO)—(NH—CHR 7 —CO)—OH  (I) or a pharmaceutically acceptable salt thereof, wherein R 1 -R 7 are defined herein. The present invention also provides a pharmaceutical composition comprising said compound and use of the same in the manufacture of a medicament for treating sequelae of ischemic cerebral stroke. The compound and pharmaceutical composition according to the present invention have good pharmacological activities so that they are able to improve significantly the symptom of sequelae of ischemic cerebral stroke.

1 . A compound of formula (I):
   H—(NH—CHR 1 —CO)—(NH—CHR 2 —CO)—(NH—CHR 3 —CO)—(NH—CHR 4 —CO)—(NH—CHR 5 —CO)—(NH—CHR 6 —CO)—(NH—CHR 2 —CO)—OH  (I)
   wherein each of R 1 , R 4  and R 6  is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, or C 2 -C 6  alkynyl;   R 2  is C 1 -C 6  alkyl which is substituted with five to ten membered heteroaryl optionally substituted with halo, hydroxyl, sulfydryl, carboxyl, amino, nitro, or cyano;   R 3  is C 1 -C 6  alkyl group substituted by halo, hydroxyl, sulfydryl, or amino;   R 5  is C 1 -C 6  alkyl substituted with carbamoyl; and   R 7  is C 1 -C 6  alkyl which is substituted with C 6 -C 14  aryl optionally substituted with halo, hydroxyl, sulfydryl, carboxyl, amino, nitro, or cyano;   or a pharmaceutically acceptable salt thereof.   
     
     
         2 . The compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein the heteroaryl is selected from five to six membered heteroaryl. 
     
     
         3 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein the five to ten membered heteroaryl is selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thienyl, iso-oxazolyl, oxadiazolyl, thiazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, furyl, indolyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl, benzimidazolyl, benzopyrazolyl, benzoxazolyl, benzoisooxazolyl, and benzothiazolyl. 
     
     
         4 . The compound or the pharmaceutically acceptable salt thereof according to any one of  claims 1 - 3 , wherein the aryl is selected from the group consisting of phenyl, naphthyl, and anthryl. 
     
     
         5 . The compound or the pharmaceutically acceptable salt thereof according to any one of  claims 1 - 3 , wherein
 the alkyl is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, iso-pentyl, neo-pentyl, and hexyl;   the alkenyl is selected from the group consisting of vinyl, propenyl, butenyl, pentenyl, and hexenyl;   the alkynyl is selected from the group consisting of ethynyl, propynyl, butynyl, pentynyl, and hexynyl.   
     
     
         6 . The compound or the pharmaceutically acceptable salt thereof according to  claim 4 , wherein
 the alkyl is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, pentyl, iso-pentyl, neo-pentyl, and hexyl;   the alkenyl is selected from the group consisting of vinyl, propenyl, butenyl, pentenyl, and hexenyl;   the alkynyl is selected from the group consisting of ethynyl, propynyl, butynyl, pentynyl, and hexynyl.   
     
     
         7 . The compound or the pharmaceutically acceptable salt thereof according to  claim 6 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound or the pharmaceutically acceptable salt thereof according to any one of  claims 1 - 3 , wherein the pharmaceutically acceptable salt is selected from the group consisting of an organic acid salt, an inorganic acid salt, an alkali metal salt, an alkali earth metal salt, and an inner salt of the compound. 
     
     
         9 . A pharmaceutical composition comprising a compound of any one of  claims 1 - 3  and optionally a pharmaceutically acceptable carrier. 
     
     
         10 . A method of treating sequelae of ischemic cerebral stroke, comprising administering a therapeutically effective amount of the compound of any one of  claims 1 - 3 .