Synthesis, in vitro and in silico NS5B polymerase inhibitory activity of benzimidazole derivatives

Med Chem. 2012 Jul;8(4):629-35. doi: 10.2174/157340612801216120.

Abstract

Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4-methylbenzyloxy)phenyl moieties, respectively, as promising leads. Binding mode of compound 6d in allosteric pocket (AP)-1 of NS5B will form the basis for future structure-activity relationship optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • Drug Design*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hepacivirus / drug effects*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Quantitative Structure-Activity Relationship
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / drug effects*

Substances

  • Benzimidazoles
  • Enzyme Inhibitors
  • Viral Nonstructural Proteins
  • benzimidazole
  • NS-5 protein, hepatitis C virus
  • DNA-Directed RNA Polymerases