Glycine alpha-ketoamides as HCV NS3 protease inhibitors

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1111-4. doi: 10.1016/s0960-894x(03)00031-3.

Abstract

Using a tetrapeptide-based alpha-ketoamide template, various amines and amino acids were incorporated to explore the prime side of the HCV NS3 protease catalytic site. Glycine carboxylic acid was found to be the most effective prime group. Further optimization yielded an inhibitor with IC(50) of 0.060 microM.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Amines / chemistry
  • Amino Acids / chemistry
  • Binding Sites
  • Glycine / analogs & derivatives
  • Glycine / chemical synthesis*
  • Glycine / pharmacology*
  • Hepacivirus / enzymology*
  • Protease Inhibitors / chemical synthesis*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / metabolism*

Substances

  • Amides
  • Amines
  • Amino Acids
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • glycine alpha-ketoamide
  • Glycine