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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Organophosphonates
Reverse Transcriptase Inhibitors
Ribose
RNA-Directed DNA Polymerase
Nucleosides
Thymidine
HIV
HIV-1
Mutation
furan
phosphonic acid

Keywords

  • Anti-HIV
  • Phosphonates
  • Resistance
  • Reverse transcriptase

ASJC Scopus subject areas

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

Cite this

Mackman, R. L., Boojamra, C. G., Prasad, V., Zhang, L., Lin, K. Y., Petrakovsky, O., ... 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

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 24, 15.12.2007, p. 6785-6789.

Research output: Contribution to journalArticle

Mackman, RL, Boojamra, CG, Prasad, V, Zhang, L, Lin, KY, Petrakovsky, O, Babusis, D, Chen, J, Douglas, J, Grant, D, Hui, HC, Kim, CU, Markevitch, DY, Vela, J, Ray, A & Cihlar, T 2007, 'Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 24, pp. 6785-6789. https://doi.org/10.1016/j.bmcl.2007.10.038
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. / Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 24. pp. 6785-6789.
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