Discovery of phenyl alanine derived ketoamides carrying benzoyl residues as novel calpain inhibitors

Bioorg Med Chem Lett. 2002 May 20;12(10):1335-8. doi: 10.1016/s0960-894x(02)00176-2.

Abstract

Novel calpain inhibitors derived from phenyl alanine aldehydes or ketoamides carrying a benzoyl residue were prepared and evaluated for their biological potency. A brief structure-activity relationship elucidated the importance of ortho-substitutents in the benzoyl moiety. The most potent derivative, the ketoamide 19c, exhibited a K(i) of 6nM and represents a novel class of reversible, highly potent and non-peptidic calpain inhibitors.

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacology
  • Blood Platelets / enzymology
  • Calpain / antagonists & inhibitors*
  • Calpain / blood
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Keto Acids / chemical synthesis*
  • Keto Acids / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Phenylalanine*
  • Structure-Activity Relationship

Substances

  • Amides
  • Cysteine Proteinase Inhibitors
  • Keto Acids
  • Phenylalanine
  • Calpain