Lefebvre I, Périgaud C, Pompon A, Aubertin A M, Girardet J L, Kirn A, Gosselin G, Imbach J L
Laboratoire de Chimie Bioorganique, URA CNRS 488, Université Montpellier II, France.
J Med Chem. 1995 Sep 29;38(20):3941-50. 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.
