Design, synthesis, and anti-HIV activity of 4′-modified carbocyclic nucleoside phosphonate reverse transcriptase inhibitors

CG Boojamra, JP Parrish, D Sperandio, Y Gao…

Index: Boojamra, Constantine G.; Parrish, Jay P.; Sperandio, David; Gao, Ying; Petrakovsky, Oleg V.; Lee, Sharon K.; Markevitch, David Y.; Vela, Jennifer E.; Laflamme, Genevieve; Chen, James M.; Ray, Adrian S.; Barron, Abraham C.; Sparacino, Mark L.; Desai, Manoj C.; Kim, Choung U.; Cihlar, Tomas; Mackman, Richard L. Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 4 p. 1739 - 1746

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Citation Number: 46

Abstract

A diphosphate of a novel cyclopentyl based nucleoside phosphonate with potent inhibition of HIV reverse transcriptase (RT)(20, IC50= 0.13 μM) has been discovered. In cell culture the parent phosphonate diacid 9 demonstrated antiviral activity EC50= 16μM, within two-fold of GS-9148, a prodrug of which is currently under clinical investigation, and within 5-fold of tenofovir (PMPA). In vitro cellular metabolism studies using 9 confirmed that the active ...