Compositions and Methods for Treating Ischemia and Ischemia-Reperfusion Injury

Abstract

The present invention relates to compositions comprising a substantially pure compound represented by Structural Formula I: and methods of using such compounds to activate cytoprotective kinases. The values and preferred values of the variables in Structural Formula I are defined herein.

What is claimed is: 
     
         1 . A composition comprising a substantially pure compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are each independently H or a hydrolyzable group, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The composition of  claim 1 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are each independently H or a hydrolyzable group, or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The composition of  claim 1 , wherein the hydrolyzable group is selected from the group consisting of C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy(C 1 -C 10 )alkyl, (C 1 -C 10 )alkoxy(C 1 -C 10 )alkoxy(C 1 -C 10 )alkyl, aryl and aryl(C 1 -C 10 )alkyl, wherein each is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, nitro, cyano, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, morpholino, phenyl, and benzyl. 
     
     
         4 . The composition of  claim 3 , wherein the hydrolyzable group is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, allyl, ethoxymethyl, methoxyethyl, methoxyethoxymethyl, methoxyethoxyethyl, benzyl, pentafluorophenyl, 2-N-(morpholino)ethyl, dimethylaminoethyl and para-methoxybenzyl. 
     
     
         5 . The composition of  claim 1 , wherein the pharmaceutically acceptable salt comprises a monovalent cation or a divalent cation. 
     
     
         6 . The composition of  claim 5 , wherein the monovalent cation is a monovalent metal cation and the divalent cation is a divalent metal cation. 
     
     
         7 . The composition of  claim 1 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The composition of  claim 1 , wherein the compound is represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A composition comprising: i) a pharmaceutically acceptable carrier or diluent; and ii) a substantially pure compound of  claim 1 .