Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1621-7. doi: 10.1016/j.bmcl.2005.12.013. Epub 2006 Jan 4.

Abstract

Depeptidization efforts of the P(3)-P(2) region of P(3) capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 are reported. We clearly established that N-methylation of the P(2) nitrogen and modification of the P(2)' carboxylic acid terminus were essential for activity in the replicon assay.

MeSH terms

  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Amides* / pharmacology
  • Binding Sites
  • Hepacivirus / chemistry
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Methylation
  • Molecular Structure
  • Nitrogen / chemistry*
  • 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

  • Amides
  • NS3 protein, hepatitis C virus
  • Serine Proteinase Inhibitors
  • Viral Nonstructural Proteins
  • Nitrogen