Synthesis and antiviral evaluation of 1-O-hexadecylpropanediol-3-P-acyclovir: Efficacy against HSV-1 infection in mice

We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavaila ble lipid prodrug of acyclovir and evaluated it for in vitro and in vivo ac tivity against herpes simplex virus infections. Although 1-O-hexadecylpropa nediol-3-P-acyclovir was less active in vitro than acyclovir, on a molar ba sis it was 2.4 times more active orally in preventing mortality from acute HSV-I infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir w as also more active than acyclovir in a thymidine kinase negative mutant st rain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus in fection in vitro due to it's ability to bypass thymidine kinase.