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 α-boranophosphonates 8 and 12 exhibited no significant in vitro activity against HIV-infected cells, neither against a broad panel of viruses, up to 200 μM. The absence of activity of target compounds 8 and 12 can be partially explained by their short half-life in culture medium.

Nucleoside α-boranophosphonate analogues of AZT and d4TFigure optionsDownload as PowerPoint slide