Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides

Richard L. Mackman, Lijun Zhang, Vidya Prasad, Constantine G. Boojamra, James Chen, Janet Douglas, Deborah Grant, Genevieve Laflamme, Hon Hui, Choung U. Kim, Jay Parrish, Antitsa D. Stoycheva, Swami Swaminathan, Ke Yu Wang, Tomas Cihlar

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T, and ddC have been synthesized. The RT inhibitory activities of the phosphonates were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity.

Original languageEnglish (US)
Pages (from-to)573-577
Number of pages5
JournalNucleosides, Nucleotides and Nucleic Acids
Volume26
Issue number6-7
DOIs
StatePublished - Jun 1 2007

Keywords

  • Antiviral
  • HIV
  • Phosphonate
  • Prodrugs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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    Mackman, R. L., Zhang, L., Prasad, V., Boojamra, C. G., Chen, J., Douglas, J., Grant, D., Laflamme, G., Hui, H., Kim, C. U., Parrish, J., Stoycheva, A. D., Swaminathan, S., Wang, K. Y., & Cihlar, T. (2007). Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides. Nucleosides, Nucleotides and Nucleic Acids, 26(6-7), 573-577. https://doi.org/10.1080/15257770701490126