Identification of 3-acetyl-2-aminoquinolin-4-one as a novel, nonpeptidic scaffold for specific calpain inhibitory activity

J Med Chem. 2009 May 14;52(9):3093-7. doi: 10.1021/jm8014734.

Abstract

A series of 3-acetyl-2-aminoquinolin-4-one derivatives selected from the Korean Chemical Bank were screened for calpain inhibitory activity by using a high-throughput fluorimetric calpain assay. We identified a potent and selective mu-calpain inhibitor, compound 17, whose specificity and efficacy for mu-calpain inhibition was better than MDL28170. Docking studies revealed that the efficacy of its inhibitory effect on calpain depended on the size and charge properties of the substitutions on the phenylamino ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Quinolones / analysis*
  • 4-Quinolones / chemistry
  • 4-Quinolones / pharmacology*
  • Aminoquinolines / analysis*
  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Calpain / antagonists & inhibitors*
  • Calpain / chemistry
  • Catalytic Domain
  • Drug Design*
  • Fluorometry
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Peptides / chemistry
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Substrate Specificity

Substances

  • 4-Quinolones
  • Aminoquinolines
  • Peptides
  • Small Molecule Libraries
  • Calpain