Mononucleoside Phosphotriester Derivatives with S-Acyl-2-thioethyl Bioreversible Phospate-Protecting Groups: Interacellular Delivery of 3'-Azido-2',3'-dideoxythymidine 5'-Monophosphate

Article abstract of DOI:10.1021/jm00020a007

The synthesis, in vitro anti-HIV-1 activity, and decomposition pathways of several mononucleoside phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) incorporating a new kind of carboxylate esterase-labile transient phosphate-protecting group, namely S-acyl-2-thioethyl, are reported.All the described compounds showed marked antiviral activity in thymidine kinase-deficient CEM cells in which AZT was virtually inactive.The results strongly support the hypothesis that such pronucleotides exert their biological effects via intracellular delivery of the 5'-mononucleotide of AZT.This point was corroborated by decomposition studies in cell extracts and culture medium.