Macrocyclic inhibitors of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3709-12. doi: 10.1016/j.bmcl.2013.05.021. Epub 2013 May 16.

Abstract

The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 μM, respectively.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Coronavirus / enzymology*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Norovirus / enzymology*
  • Peptide Hydrolases / metabolism*
  • Picornaviridae / enzymology*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Macrocyclic Compounds
  • Protease Inhibitors
  • Peptide Hydrolases