Acyl deoxyribonucleoside derivatives and uses thereof

Abstract

The invention relates to compositions comprising acyl derivatives of 2′-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced cellular damage, methods for improving wound healing and tissue repair, and methods for ameliorating the effects of aging comprising administering the compositions of the present invention to an animal.

1 - 55  (cancelled).  
     
     
         56 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxyadenosine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , and R 3  are the same or different and each is hydrogen or an acyl group derived from  
         (a) an unbranched fatty acid with 3 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid having 3 to 22 carbon atoms, provided that not all of R 1 , R 2 , and R 3  are H, and where R 3  is not H, then R 1  and/or R 2  may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         57 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxyguanosine having the formula  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , and R 3  are the same or different and each is hydrogen or an acyl group derived from  
         (a) an unbranched fatty acid with 3 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, phenylalanine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid having 3 to 22 carbon atoms, provided that not all of R 1 , R 2 , and R 3  are H, and where R 3  is not H, then R 1  and/or R 2  may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         58 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxycytidine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , and R 3  are the same or different and each is hydrogen or an acyl group derived from  
         (a) an unbranched fatty acid with 3 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid having 3 to 22 carbon atoms, provided that not all of R 1 , R 2,  and R 3  are H, and where R 3  is not H, then R 1  and/or R 2  may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         59 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxythymidine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1  is an acyl group derived from  
         (a) an unbranched fatty acid with 3 to 15 or 17 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid having 3 to 22 carbon atoms, and R 2  and R 3  are H, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         60 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxythymidine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1  is H, R 2  is an acyl group derived from  
         (a) an unbranched fatty acid with 3 to 13 or 15 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid with 3 to 22 carbon atoms, and R 3  is H or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         61 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxythymidine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are the same or different and each is an acyl group derived from  
         (a) an unbranched fatty acid with 5 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid, or  
         (d) a dicarboxylic acid with 3 to 22 carbon atoms, and R 3  is H or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         62 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an acyl derivative of 2′-deoxythymidine, having the formula  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are the same or different and each is an acyl group derived from  
         (a) an unbranched fatty acid with 2 to 22 carbon atoms,  
         (b) an amino acid selected from the group consisting of glycine, the L forms of alanine, valine, leucine, isoleucine, tyrosine, proline, hydroxyproline, serine, threonine, cysteine, aspartic acid, glutamic acid, arginine, lysine, histidine, carnitine, and ornithine,  
         (c) nicotinic acid or  
         (d) a dicarboxylic acid with 3 to 22 carbon atoms, and R 3  is an acyl group derived from an optionally substituted benzoyl or heterocyclic carboxylic acid that is substantially nontoxic, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
       
     
     
         63 . A method for treating or preventing radiation-induced cellular damage or sunlight-induced cellular damage comprising administering to an animal an effective amount of a composition comprising an effective amount of each of at least two compounds selected from at least two of the groups of compounds having formulae  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , and R 3  are the same or different and each is H or an acyl group derived from a carboxylic acid, provided that at least one of said substituents R 1 , R 2 , and R 3  on each of said groups of compounds is not hydrogen, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier.