Details for Patent: 6,306,834
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Title: | 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 biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal. |
Inventor(s): | von Borstel; Reid Warren (Darnestown, MD), Bamat; Michael Kevin (Darnestown, MD) |
Assignee: | Pro-Neuron, Inc. (N/A) |
Filing Date: | Jun 07, 1995 |
Application Number: | 08/479,516 |
Claims: | 1. A method of enhancing the delivery of exogenous 2'-deoxyadenosine to the tissue of an animal, comprising the step of administering to said animal of an acyl derivative of 2'-deoxyadenosine, having the formula ##STR19## wherein R.sub.1, R.sub.2 and R.sub.3 are the same or different and each of H or an acyl group derived from a carboxylic acid, provided that at least one of R.sub.1, R.sub.2 and R.sub.3 is not hydrogen. 2. A method as in claim 1 wherein R.sub.1, R.sub.2, and R.sub.3 are the same or different and each is hydrogen or 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 having 3 to 22 carbon atoms, provided that not all of R.sub.1, R.sub.2, and R.sub.3 are H, or a pharmaceutically acceptable salt thereof. 3. A method as in claim 2 wherein R.sub.1, R.sub.2 and R.sub.3 are the same or different and each is H or an acyl group derived from an unbranched fatty acid with 2 to 22 carbon atoms. 4. A method as in claim 3 wherein R.sub.1 and R.sub.2 are fatty acids with 6 to 16 carbon atoms. 5. A method of enhancing the delivery of exogenous 2'-deoxyguanosine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxyguanosine having the formula ##STR20## wherein R.sub.1, R.sub.2 and R.sub.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 R.sub.1, R.sub.2 and R.sub.3 is not hydrogen. 6. A method as in claim 5 wherein R.sub.1, R.sub.2, and R.sub.3 are the same or different and each is hydrogen or 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, phenylalanine, carnitine, and ornithine, (c) nicotinic acid, or (d) a dicarboxylic acid having 3 to 22 carbon atoms, provided that not all of R.sub.1, R.sub.2, and R.sub.3 are H, or a pharmaceutically acceptable salt thereof. 7. A method as in claim 2 wherein R.sub.1, R.sub.2 and R.sub.3 are the same or different and each is H or an acyl group derived from an unbranched fatty acid with 2 to 22 carbon atoms. 8. A method as in claim 3 wherein R.sub.1 and R.sub.2 are fatty acids with 6 to 16 carbon atoms. 9. A method of enhancing the delivery of exogenous 2'-deoxycytidine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxycytidine, having the formula ##STR21## wherein R.sub.1, R.sub.2 and R.sub.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 R.sub.1, R.sub.2 and R.sub.3 is not hydrogen. 10. A method as in claim 9 wherein R.sub.1, R.sub.2, and R.sub.3 are the same or different and each is hydrogen or 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 having 3 to 22 carbon atoms, provided that not all of R.sub.1, R.sub.2, and R.sub.3 are H, or a pharmaceutically acceptable salt thereof. 11. A method as in claim 2 wherein R.sub.1, R.sub.2 and R.sub.3 are the same or different and each is H or an acyl group derived from an unbranched fatty acid with 2 to 22 carbon atoms. 12. A method as in claim 3 wherein R.sub.1 and R.sub.2 are fatty acids with 6 to 16 carbon atoms. 13. A method of enhancing the delivery of exogenous 2'-deoxythymidine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxythymidine, having the formula ##STR22## wherein R.sub.1 is an acyl group derived from (a) an unbranched fatty acid with 2 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, or a pharmaceutically acceptable salt thereof. 14. A method as in claim 13 wherein R.sub.1 is an unbranched fatty acid with 2 to 15 or 17 to 22 carbon atoms. 15. A method as in claim 14 wherein R.sub.1 is an unbranched fatty acid with 2 to 4 carbon atoms. 16. A method of enhancing the delivery of exogenous 2'-deoxythymidine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxythymidine, having the formula ##STR23## wherein R.sub.2 is an acyl group derived from (a) an unbranched fatty acid with 2 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, or a pharmaceutically acceptable salt thereof. 17. A method as in claim 16 wherein R.sub.2 is an unbranched fatty acid with 2 to 13 or 15 to 22 carbon atoms. 18. A method as in claim 17 wherein R.sub.2 is an unbranched fatty acid with 2 to 4 carbon atoms. 19. A method of enhancing the delivery of exogenous 2'-deoxythymidine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxythymidine, having the formula ##STR24## wherein R.sub.1 and R.sub.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, or a pharmaceutically acceptable salt thereof. 20. A method as in claim 19 wherein R.sub.1 and R.sub.2 are the same or different and each is an unbranched fatty acid with 2 to 22 carbon atoms. 21. A method as in claim 20 wherein R.sub.1 and R.sub.2 are the same or different and each is an unbranched fatty acid with 2 to 4 carbon atoms. 22. A method of enhancing the delivery of exogenous 2'-deoxythymidine to the tissue of an animal, comprising the step of administering to said animal an acyl derivative of 2'-deoxythymidine, having the formula ##STR25## wherein R.sub.1 and R.sub.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.sub.3 is an acyl group derived from an optionally substituted benzoyl or heterocyclic acid that is substantially nontoxic, or a pharmaceutically acceptable salt thereof. 23. A method as in claim 22 wherein R.sub.1 and R.sub.2 are the same or different and each is an unbranched fatty acid with 2 to 22 carbon atoms. 24. A method as in claim 23 wherein R.sub.1 and R.sub.2 are the same or different and each is an unbranched fatty acid with 2 to 4 carbon atoms. 25. A method as in claim 23 wherein R.sub.3 is an acyl group derived from nicotinic acid, benzoic acid, or para-aminobenzoic acid. |