1. Academic Validation
  2. S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: synthesis, antiviral activity, and stability study

S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: synthesis, antiviral activity, and stability study

  • J Med Chem. 2003 Feb 27;46(5):782-93. doi: 10.1021/jm021016y.
Suzanne Peyrottes 1 Gaëlle Coussot Isabelle Lefebvre Jean-Louis Imbach Gilles Gosselin Anne-Marie Aubertin Christian Périgaud
Affiliations

Affiliation

  • 1 UMR 5625 CNRS-UMII, Université Montpellier II, Case Courrier 008, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
Abstract

The synthesis, Antiviral activity, and stability study of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing modified l-tyrosinyl residues are reported. These compounds were obtained via phosphoramidite (P(III)) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various Cell Culture experiments, with EC(50) values between the micro- and nanomolar range, especially in thymidine kinase deficient (TK(-)) cells, showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters successively involves an esterase and a phosphodiesterase hydrolysis.

Figures