2. Academic Validation
  3. Design, synthesis, and anti-HIV activity of 4'-modified carbocyclic nucleoside phosphonate reverse transcriptase inhibitors

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

  • Bioorg Med Chem. 2009 Feb 15;17(4):1739-46. doi: 10.1016/j.bmc.2008.12.028.
Constantine G Boojamra 1,  Jay P Parrish,  David Sperandio,  Ying Gao,  Oleg V Petrakovsky,  Sharon K Lee,  David Y Markevitch,  Jennifer E Vela,  Genevieve Laflamme,  James M Chen,  Adrian S Ray,  Abraham C Barron,  Mark L Sparacino,  Manoj C Desai,  Choung U Kim,  Tomas Cihlar,  Richard L Mackman
Affiliations

Affiliation

  • 1 Gilead Science, Inc, Foster City, CA 94404, USA. dboojamra@gilead.com
PMID: 19179082 DOI: 10.1016/j.bmc.2008.12.028
Abstract

A diphosphate of a novel cyclopentyl based nucleoside phosphonate with potent inhibition of HIV Reverse Transcriptase (RT) (20, IC(50)=0.13 microM) has been discovered. In Cell Culture the parent phosphonate diacid 9 demonstrated Antiviral activity EC(50)=16 microM, 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 diphosphate metabolite is produced albeit at a lower efficiency relative to GS-9148.

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