Discovery of 4'-azido-2'-deoxy-2'-C-methyl cytidine and prodrugs thereof: a potent inhibitor of Hepatitis C virus replication

Bioorg Med Chem Lett. 2012 May 1;22(9):3265-8. doi: 10.1016/j.bmcl.2012.03.021. Epub 2012 Mar 16.

Abstract

4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) value of 1.2 μM and showing moderate in vivo bioavailability in rat (F=14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Discovery
  • Hepacivirus / drug effects*
  • Prodrugs / pharmacology*
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • Rats
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Prodrugs
  • Viral Nonstructural Proteins
  • Deoxycytidine
  • Cytidine
  • 4'-azido-2'-deoxy-2'-methylcytidine
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase