Peptidyl human heart chymase inhibitors. 1. Synthesis and inhibitory activity of difluoromethylene ketone derivatives bearing P' binding subsites

Bioorg Med Chem Lett. 1998 Apr 21;8(8):913-8. doi: 10.1016/s0960-894x(98)00131-0.

Abstract

Peptidyl difluoromethylene ketone derivatives were designed to take advantage of probable additional interactions with the S' subsite of human heart chymase. They showed potent inhibitory activities against human heart chymase and were more efficient than bovine chymotrypsin.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cattle
  • Chymases
  • Chymotrypsin / antagonists & inhibitors*
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology
  • Humans
  • Indicators and Reagents
  • Ketones / chemical synthesis*
  • Ketones / chemistry
  • Ketones / pharmacology
  • Kinetics
  • Models, Molecular
  • Molecular Structure
  • Myocardium / enzymology*
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Dipeptides
  • Indicators and Reagents
  • Ketones
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • Chymotrypsin
  • Chymases