Pkc-activating compounds for the treatment of neurodegenerative diseases

Abstract

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

1 .- 51 . (canceled) 
     
     
         52 . An epoxidized polyunsaturated fatty acid (PUFA) ester compound wherein at least one carbon-carbon unsaturated bond in said PUFA is epoxidized, wherein the epoxidized polyunsaturated fatty acid (PUFA) ester has any of the following formulas: CH 3 (CH 2 ) 4 (CH═CHCH 2 ) x (CH 2 ) y COOR or CH 3 CH 2 (CH═CHCH 2 )x(CH 2 ) y COOR, wherein x is 2-6, y is 2-6, and R is alkyl, wherein at least one carbon-carbon unsaturated bond in said epoxidized PUFA is epoxidized. 
     
     
         53 . The compound of  claim 52 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group. 
       
     
     
         54 . The compound of  claim 53 , wherein R is methyl. 
     
     
         55 . A pharmaceutical composition comprising a compound of  claim 52  and a pharmaceutically acceptable carrier. 
     
     
         56 . A method of activating an epsilon isoform of protein kinase C in a patient in need thereof comprising administering an effective amount of an epoxidized polyunsaturated fatty acid (PUFA) ester compound wherein at least one carbon-carbon unsaturated bond in said PUFA is epoxidized, wherein the epoxidized polyunsaturated fatty acid (PUFA) ester has any of the following formulas: CH 3 (CH 2 ) 4 (CH═CHCH 2 ) x (CH 2 ) y COOR or CH 3 CH 2 (CH═CHCH 2 )x(CH 2 ) y COOR, wherein x is 2-6, y is 2-6, and R is alkyl, wherein at least one carbon-carbon unsaturated bond in said epoxidized PUFA is epoxidized. 
     
     
         57 . The method of  claim 56 , wherein the epoxidized PUFA has the formula: 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group; or a pharmaceutically acceptable salt thereof. 
       
     
     
         58 . The method of  claim 57 , wherein R is methyl. 
     
     
         59 . A method of treating a neurological disease comprising administering to a patient in need thereof an effective amount of an epoxidized polyunsaturated fatty acid (PUFA) ester compound wherein at least one carbon-carbon unsaturated bond in said PUFA is epoxidized, wherein the epoxidized polyunsaturated fatty acid (PUFA) ester has any of the following formulas: CH 3 (CH 2 ) 4 (CH═CHCH 2 ) x (CH 2 ) y COOR or CH 3 CH 2 (CH═CHCH 2 )x(CH 2 ) y COOR, wherein x is 2-6, y is 2-6, and R is alkyl, wherein at least one carbon-carbon unsaturated bond in said epoxidized PUFA is epoxidized. 
     
     
         60 . The method of  claim 59  wherein the neurological disease is Alzheimer's disease. 
     
     
         61 . The method of  claim 59  wherein the neurological disease is stroke.