Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3655-8. doi: 10.1016/j.bmcl.2004.05.021.

Abstract

A series of keto-glutamine tetrapeptide analogs containing a 2-oxo-pyrrolidine ring as a glutamine side chain mimic were synthesized with both R and S configuration at the beta-carbon. Compounds bearing a phthalhydrazide moiety show improved reversible inhibition of HAV 3C proteinase in the low micromolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3C Viral Proteases
  • Cysteine Endopeptidases
  • Glutamine / analogs & derivatives
  • Glutamine / chemistry
  • Glutamine / pharmacology*
  • Hepatitis A virus / drug effects*
  • Hepatitis A virus / enzymology
  • Inhibitory Concentration 50
  • Molecular Mimicry
  • Oligopeptides / chemical synthesis
  • Phthalazines / chemistry
  • Phthalazines / pharmacology
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • Viral Proteins / antagonists & inhibitors*

Substances

  • Oligopeptides
  • Phthalazines
  • Protease Inhibitors
  • Pyrrolidines
  • Viral Proteins
  • Glutamine
  • Cysteine Endopeptidases
  • 3C Viral Proteases
  • pyrrolidine