Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1628-32. doi: 10.1016/j.bmcl.2005.12.046. Epub 2006 Jan 18.

Abstract

Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of approximately 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections.

MeSH terms

  • Binding Sites
  • Bridged Bicyclo Compounds* / chemical synthesis
  • Bridged Bicyclo Compounds* / chemistry
  • Bridged Bicyclo Compounds* / pharmacology
  • Hepacivirus / chemistry
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Molecular Structure
  • Protein Binding
  • Replicon / drug effects*
  • Serine Proteinase Inhibitors* / chemical synthesis
  • Serine Proteinase Inhibitors* / chemistry
  • Serine Proteinase Inhibitors* / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry
  • X-Ray Diffraction

Substances

  • 2-azabicyclo(2.2.1)heptane-3-carboxylic acid
  • Bridged Bicyclo Compounds
  • NS3 protein, hepatitis C virus
  • Serine Proteinase Inhibitors
  • Viral Nonstructural Proteins