Synthesis and structure-activity relationships of novel anti-hepatitis C agents: N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives

J Med Chem. 2005 Oct 6;48(20):6454-60. doi: 10.1021/jm058223t.

Abstract

Several 6- and 7-monosubstituted N3,5'-cyclo-4-(beta-d-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives as well as the 5-thiono analogue were synthesized, providing structure-anti-hepatitis C virus (HCV) activity relationships for the series. Among the compounds synthesized, the 6-bromo, 7-methylamino, and 5-thiono analogues exhibited more potent anti-HCV activity in an HCV subgenomic replicon cell based assay (EC90 = 1.9, 7.4, and 10.0 microM, respectively) than the lead compound N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one (EC90 = 79.8 microM).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology
  • Cell Line, Tumor
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Humans
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Nucleosides / pharmacology
  • RNA, Viral / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Bridged-Ring Compounds
  • Nucleosides
  • RNA, Viral