Prolyl endopeptidase inhibitors

Farmaco. 2000 Mar;55(3):188-90. doi: 10.1016/s0014-827x(00)00018-5.

Abstract

Selective prolyl endopeptidase inhibitors were elaborated by modification of the structure of SUAM-1221, by using a CoMFA study and protein crystallography. The most active representatives of omega-(N-hetaryl)alkanoylprolylpyrrolidines, containing 2- or 3-methylene chain links have high activity (IC50 10(-9)-10(-11)) and exhibit significant in vivo activities.

MeSH terms

  • Animals
  • Crystallography
  • Endopeptidases / metabolism*
  • In Vitro Techniques
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Pyrroles / chemical synthesis
  • Pyrroles / pharmacology
  • Rats
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Protease Inhibitors
  • Pyrroles
  • Serine Proteinase Inhibitors
  • N-(N-(phenyl)butyryl-L-prolyl)pyrrolidine
  • Endopeptidases