Synthesis and antiviral activity of boranophosphonate isosteres of AZT and d4T monophosphates.
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.
Barral
Karine
K
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.
Priet
Stéphane
S
De Michelis
Céline
C
Sire
Joséphine
J
Neyts
Johan
J
Balzarini
Jan
J
Canard
Bruno
B
Alvarez
Karine
K
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*
D000998:Antiviral Agents; D063065:Organophosphonates; D015215:Zidovudine; D018119:Stavudine