Synthesis and Antiviral Evaluation of 3'-Fluoro-4'-modified-5'-norcarbocyclic Nucleoside Phosphonates

ChemMedChem. 2019 Mar 5;14(5):522-526. doi: 10.1002/cmdc.201800804. Epub 2019 Jan 31.

Abstract

The synthesis and anti-HIV evaluation of hitherto unknown 3'-fluoro-5'-norcarbocyclic nucleoside phosphonates bearing adenine with modifications at the 4' position (ethynyl, vinyl, ethyl, hydroxymethyl) is described. One of the synthesized compounds was found to be an inhibitor of HIV-1 replication, but with moderate efficiency relative to (R)-9-(2-phosphonylmethoxypropyl)adenine ((R)-PMPA, tenofovir), with no concomitant cytotoxicity.

Keywords: 3′-fluoro-5′-norcarbocyclic nucleosides; anti-HIV; antiviral agents; phosphonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / chemistry
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology*
  • Blood Cells
  • Cell Survival / drug effects
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Molecular Structure
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology*
  • Organophosphonates / chemistry*
  • Structure-Activity Relationship
  • Tenofovir / pharmacology
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Nucleosides
  • Organophosphonates
  • Tenofovir
  • Adenine