Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4210-4. doi: 10.1016/j.bmcl.2008.05.068. Epub 2008 May 20.

Abstract

The structure-based design, chemical synthesis and in vitro activity evaluation of various falcipain inhibitors derived from 2-pyridone are reported. These compounds contain a peptidomimetic binding determinant and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Malaria / drug therapy
  • Models, Chemical
  • Molecular Conformation
  • Plasmodium falciparum / metabolism
  • Pyridones / chemistry*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Cysteine Proteinase Inhibitors
  • Pyridones
  • Cysteine Endopeptidases
  • falcipain 2
  • falcipain 3