Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. Part 7: structure-activity studies of bicyclic 2-pyridone-containing peptidomimetics

Bioorg Med Chem Lett. 2002 Mar 11;12(5):733-8. doi: 10.1016/s0960-894x(02)00008-2.

Abstract

The structure-based design, chemical synthesis, and biological evaluation of bicyclic 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. An optimized compound is shown to exhibit antiviral activity when tested against a variety of HRV serotypes (EC(50)'s ranging from 0.037 to 0.162 microM).

MeSH terms

  • 3C Viral Proteases
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Line
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Molecular Mimicry
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology
  • Rhinovirus / drug effects
  • Rhinovirus / enzymology*
  • Serotyping
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cysteine Proteinase Inhibitors
  • Pyridones
  • Viral Proteins
  • 2-hydroxypyridine
  • Cysteine Endopeptidases
  • 3C Viral Proteases