title: Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates.
abstract: We report synthesis, in vitro antiviral activity, and stability studies in biological media of original boranophosphonate isosteres of AZT and d4T monophophates. A convenient route for the synthesis of 3'-Azido-3'-deoxythymidine-5'-boranophosphonate 8 and 2',3'-Didehydro-3'-dideoxythymidine-5'-boranophosphonate 12 is described. H-phosphinates 7 and 11, and alpha-boranophosphonates 8 and 12 exhibited no significant in vitro activity against HIV-infected cells, neither against a broad panel of viruses, up to 200 microM. The absence of activity of target compounds 8 and 12 can be partially explained by their short half-life in culture medium.
authors.affiliation: Laboratoire d'Architecture et Fonction des Macromolécules Biologiques, UMR CNRS 6098, Equipe Réplicases Virales, Structure, Mécanisme, et Drug-design, Universités Aix-Marseille I et II, Parc scientifique de Luminy, 163 av de Luminy, Case 932, 13288 Marseille Cedex 9, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Barral
authors.forename: Stéphane
authors.initials: S
authors.lastname: Priet
authors.forename: Céline
authors.initials: C
authors.lastname: De Michelis
authors.forename: Joséphine
authors.initials: J
authors.lastname: Sire
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
authors.forename: Karine
authors.initials: K
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018119:Stavudine / Q000031:analogs & derivatives*; D014780:Viruses / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D015215:Zidovudine; D018119:Stavudine