Novel, potent phenethylamide inhibitors of the hepatitis C virus (HCV) NS3 protease: probing the role of P2 aryloxyprolines with hybrid structures

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2745-8. doi: 10.1016/s0960-894x(03)00536-5.

Abstract

Synthesis of hybrid HCV NS3 protease/NS4A inhibitors having the 4,4-difluoroaminobutyric acid (difluoroAbu) phenethylamides as P1-P1' and quinolyloxyprolines as P2 fragments led to 7 (IC(50) 54 nM). Molecular modelling suggests that this potent tripeptide inhibitor utilizes interactions in the S1', S1, S2, S3 and S4 sites of the protease.

Publication types

  • Comparative Study

MeSH terms

  • Aminobutyrates / chemistry
  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Hydroquinones / chemistry
  • Hydroxyproline / chemistry
  • Models, Molecular
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • RNA Helicases
  • Serine Endopeptidases
  • Stereoisomerism
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins

Substances

  • Aminobutyrates
  • Aniline Compounds
  • Antiviral Agents
  • Hydroquinones
  • NS3 protein, flavivirus
  • Oligopeptides
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Serine Endopeptidases
  • RNA Helicases
  • Hydroxyproline