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

RL Mackman, CG Boojamra, V Prasad, L Zhang…

Index: Mackman, Richard L.; Boojamra, Constantine G.; Prasad, Vidya; Zhang, Lijun; Lin, Kuei-Ying; Petrakovsky, Oleg; Babusis, Darius; Chen, James; Douglas, Janet; Grant, Deborah; Hui, Hon C.; Kim, Choung U.; Markevitch, David Y.; Vela, Jennifer; Ray, Adrian; Cihlar, Tomas Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 24 p. 6785 - 6789

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Citation Number: 29

Abstract

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.