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

Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):573-7. doi: 10.1080/15257770701490126.

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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Cyclization / drug effects
  • Drug Resistance, Viral / drug effects
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / chemistry
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Zidovudine / chemistry
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Nucleosides
  • Organophosphonates
  • Prodrugs
  • Reverse Transcriptase Inhibitors
  • Zidovudine