Document 0329
 DOCN  M9610329
 TI    Mononucleoside phosphotriester derivatives with S-acyl-2-thioethyl
       bioreversible phosphate-protecting groups: intracellular delivery of
       3'-azido-2',3'-dideoxythymidine 5'-monophosphate.
 DT    9601
 AU    Lefebvre I; Perigaud C; Pompon A; Aubertin AM; Girardet JL; Kirn A;
       Gosselin G; Imbach JL; Laboratoire de Chimie Bioorganique, URA CNRS 488,
       Universite; Montpellier II, France.
 SO    J Med Chem. 1995 Sep 29;38(20):3941-50. Unique Identifier : AIDSLINE
       MED/96005091
 AB    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.
 DE    Antiviral Agents/*CHEMICAL SYNTHESIS/METABOLISM/PHARMACOLOGY  Biological
       Transport  Cell Line  Drug Stability  HIV-1/*DRUG EFFECTS  Support,
       Non-U.S. Gov't  Thymine Nucleotides/*PHARMACOKINETICS
       Zidovudine/*ANALOGS & DERIVATIVES/PHARMACOKINETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).