Discovery of a novel bicycloproline P2 bearing peptidyl alpha-ketoamide LY514962 as HCV protease inhibitor

Bioorg Med Chem Lett. 2004 Jan 5;14(1):251-6. doi: 10.1016/j.bmcl.2003.09.074.

Abstract

We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles.

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / pharmacology
  • Dipeptides / chemical synthesis
  • Dipeptides / pharmacology
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Humans
  • Male
  • Proline / chemistry*
  • Proline / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / pharmacology*
  • Viral Nonstructural Proteins / metabolism*

Substances

  • Bridged Bicyclo Compounds
  • Dipeptides
  • NS3 protein, hepatitis C virus
  • Serine Proteinase Inhibitors
  • Viral Nonstructural Proteins
  • Proline
  • Serine Endopeptidases