Studies on acyl pyrrolidine inhibitors of HCV RNA-dependent RNA polymerase to identify a molecule with replicon antiviral activity

Bioorg Med Chem Lett. 2007 Apr 1;17(7):1930-3. doi: 10.1016/j.bmcl.2007.01.034. Epub 2007 Jan 19.

Abstract

The SAR development is described for a series of N-acyl pyrrolidine inhibitors of the Hepatitis C virus RNA-dependent RNA polymerase, NS5B, from tractable Delta21 enzyme inhibitors to an example with antiviral activity in a cellular assay (HCV replicon).

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Hepacivirus / chemistry*
  • Hepacivirus / genetics*
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Conformation
  • Pyrrolidines / antagonists & inhibitors*
  • RNA, Viral / chemistry
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Replicon / genetics*
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / pharmacology*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Pyrrolidines
  • RNA, Viral
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase
  • pyrrolidine