Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres

  • J Med Chem. 2002 Jul 18;45(15):3321-4. doi: 10.1021/jm0208323.
Luc Rocheblave  1 ,  Frédéric Bihel ,  Céline De Michelis ,  Ghislaine Priem ,  Jérôme Courcambeck ,  Brice Bonnet ,  Jean-Claude Chermann ,  Jean-Louis Kraus
Affiliations
  • 1. Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, case 901, Université de la Méditerranée, 70 route Léon Lachamp, 13288 Marseille Cedex 9, France.
PMID: 12109915 DOI: 10.1021/jm0208323
Abstract

Starting from the chemical structure of the recent FDA-approved anti-HIV drug Amprenavir (Agenerase), a potent HIV-protease inhibitor, we have designed new series of Amprenavir bioisoteres in which the methylene group of the benzyl group was replaced by a sulfur atom. This structural modification has required an original multistep synthesis. Unfortunately, introduction of the sulfur atom abolished or drastically decreased both inhibitory activity on recombinant HIV Protease and HIV Infection protection on MT4 cell cultures.