Structure-based design of ketone-containing, tripeptidyl human rhinovirus 3C protease inhibitors

Bioorg Med Chem Lett. 2000 Jan 3;10(1):45-8. doi: 10.1016/s0960-894x(99)00587-9.

Abstract

Tripeptide-derived molecules incorporating C-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). An optimized example of such compounds displayed potent 3CP inhibition activity (K = 0.0045 microM) and in vitro antiviral properties (EC50=0.34 microM) when tested against HRV serotype-14.

Publication types

  • Comparative Study

MeSH terms

  • 3C Viral Proteases
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Ketones / chemical synthesis*
  • Ketones / pharmacology
  • Kinetics
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Rhinovirus / drug effects
  • Rhinovirus / enzymology*
  • Structure-Activity Relationship
  • Viral Proteins*

Substances

  • Antiviral Agents
  • Cysteine Proteinase Inhibitors
  • Ketones
  • Oligopeptides
  • Viral Proteins
  • Cysteine Endopeptidases
  • 3C Viral Proteases