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

Richard L. Mackman, Constantine G. Boojamra, Vidya Prasad, Lijun Zhang, Kuei Ying Lin, Oleg Petrakovsky, Darius Babusis, James Chen, Janet Douglas, Deborah Grant, Hon C. Hui, Choung U. Kim, David Y. Markevitch, Jennifer Vela, Adrian Ray, Tomas Cihlar

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6785-6789
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number24
DOIs
StatePublished - Dec 15 2007

Keywords

  • Anti-HIV
  • Phosphonates
  • Resistance
  • Reverse transcriptase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Mackman, R. L., Boojamra, C. G., Prasad, V., Zhang, L., Lin, K. Y., Petrakovsky, O., Babusis, D., Chen, J., Douglas, J., Grant, D., Hui, H. C., Kim, C. U., Markevitch, D. Y., Vela, J., Ray, A., & Cihlar, T. (2007). Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates. Bioorganic and Medicinal Chemistry Letters, 17(24), 6785-6789. https://doi.org/10.1016/j.bmcl.2007.10.038