Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2683-6. doi: 10.1016/s0960-894x(01)00542-x.

Abstract

Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the P(2)-P(3) amide bond were investigated as irreversible inhibitors of the human rhinovirus (HRV) 3C protease (3CP). When screened against HRV serotype-14 the best compound was shown to have very good 3CP inhibition (k(obs)/[I]=270,000M(-1)s(-1)) and potent in vitro antiviral activity (EC(50)=7.0nM).

MeSH terms

  • 3C Viral Proteases
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cysteine Endopeptidases / metabolism
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Rhinovirus / drug effects
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Peptides
  • Protease Inhibitors
  • Viral Proteins
  • Cysteine Endopeptidases
  • 3C Viral Proteases