Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates

A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC50 = 2.1 μM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.

A series of ribose and nucleobase modified nucleoside phosphonates have been synthesized and their potency toward wild-type HIV reverse transcriptase (RT) and several mutant strains of RT evaluated.Figure optionsDownload as PowerPoint slide