Design and synthesis of spiro-cyclopentenyl and spiro-[1,3]-dithiolanyl substituted pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease

Bioorg Med Chem Lett. 2003 May 19;13(10):1657-60. doi: 10.1016/s0960-894x(03)00274-9.

Abstract

Using the pyrrolidine-5,5-trans-lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 2b, with a spiro-cyclobutyl P1 substituent and an isopropyl carbonyl substituent at the lactam nitrogen, has an IC(50) value in the replicon cell-based assay of 3 microM.

MeSH terms

  • Drug Design
  • Drug Stability
  • Inhibitory Concentration 50
  • Lactams / chemical synthesis
  • Lactams / pharmacology*
  • Protease Inhibitors / chemical synthesis*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Lactams
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Spiro Compounds
  • Viral Nonstructural Proteins