2'-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6264-7. doi: 10.1016/j.bmcl.2009.09.116. Epub 2009 Oct 3.

Abstract

We report the preparation of 2'-alpha-F, 2'-beta-F and 2',2'-difluoro analogues of the leading anti-varicella zoster virus (VZV) pentylphenyl BCNA Cf 1743. VZV thymidine kinase showed the highest phosphorylating capacity for the beta-fluoro derivative, that retained equal antiviral potency as the parent compound. In contrast, the alpha-fluoro- and 2',2'-difluoro BCNA derivatives were markedly less (approximately 100-fold) antivirally active.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / pharmacology
  • Bromodeoxyuridine / chemistry
  • Bromodeoxyuridine / pharmacology
  • Cell Line
  • Drug Design*
  • Drug Interactions
  • Fluorides / chemistry
  • HeLa Cells
  • Herpesvirus 3, Human / drug effects*
  • Herpesvirus 3, Human / metabolism
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Pyrimidine Nucleosides / administration & dosage
  • Pyrimidine Nucleosides / pharmacology*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thymidine Kinase / metabolism
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Bridged Bicyclo Compounds
  • Cf 1743
  • Nucleosides
  • Pyrimidine Nucleosides
  • Thymidine Kinase
  • Bromodeoxyuridine
  • Fluorides