Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling

J Med Chem. 2003 Jan 30;46(3):345-8. doi: 10.1021/jm025594q.

Abstract

The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / chemistry
  • Models, Molecular
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry

Substances

  • Amides
  • Benzene Derivatives
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Viral Nonstructural Proteins