Details for Patent: 7,169,765

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 W. (Kensington, MD), Bamat; Michael K. (Potomac, MD)
Assignee:	Wellstat Therapeutics Corporation (Gaithersburg, MD)
Filing Date:	Jan 31, 2000
Application Number:	09/494,243
Claims:	1. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxyadenosine, having the formula ##STR00019## 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 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.sub.1, R.sub.2, and R.sub.3 are H, and where R.sub.3 is not H, then R.sub.1 and/or R.sub.2 may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 2. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxyguanosine having the formula ##STR00020## 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 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.sub.1, R.sub.2, and R.sub.3 are H, and where R.sub.3 is not H, then R.sub.1 and/or R.sub.2 may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 3. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxycytidine, having the formula ##STR00021## 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 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.sub.1, R.sub.2, and R.sub.3 are H, and where R.sub.3 is not H, then R.sub.1 and/or R.sub.2 may also be acetyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 4. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxythymidine, having the formula ##STR00022## wherein R.sub.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.sub.2 and R.sub.3 are H, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 5. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxythymidine, having the formula ##STR00023## wherein R.sub.1 is H, R.sub.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.sub.3 is H or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 6. A method for treating mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxythymidine, having the formula ##STR00024## 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 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.sub.3 is H or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 7. A method for treating a mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof an effective amount of a composition comprising an acyl derivative of 2'-deoxythymidine, having the formula ##STR00025## 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 carboxylic acid that is substantially nontoxic, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 8. A method for treating a mutagen-induced cellular damage in an animal comprising administering to an animal in need thereof 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 ##STR00026## 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 said substituents R.sub.1, R.sub.2, and R.sub.3 on each of said groups of compounds is not hydrogen, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier.