Synthesis and in vitro antiviral activity of 3'-O-acyl derivatives of 5'-amino-5'-deoxythymidine: potential prodrugs for topical application.
A series of 3'-O-acyl derivatives of 5'-amino-5'-deoxythymidine (5'-NH2-TdR) (IIIa-j) was synthesized by acylation of 5'-azido-5'-deoxythymidine (I). The resulting acetoxy azides were reduced by catalytic hydrogenation to give the corresponding amines. The antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro, the aqueous solubilities, and the octanol-water partition coefficients of these compounds were determined. All these derivatives have shown potency against HSV-1 virus similar to the parent compound, except the aromatic and highly branched aliphatic esters, IIIi and IIIj, which are less active. Because of their markedly improved lipophilicity, these compounds are believed to penetrate the biological membranes more easily, and thus, would be more effective for the topical treatment of cutaneous herpes virus infections.
D000287:Administration, Topical; D000998:Antiviral Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D015224:Dideoxynucleosides; D009682:Magnetic Resonance Spectroscopy; D018139:Simplexvirus / Q000187:drug effects; D012995:Solubility; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C024082:5'-amino-5'-deoxythymidine; D013936:Thymidine