1-Oxacephem-based human chymase inhibitors: discovery of stable inhibitors in human plasma

Bioorg Med Chem Lett. 2000 Nov 6;10(21):2403-6. doi: 10.1016/s0960-894x(00)00489-3.

Abstract

1-Oxacephem derivatives were evaluated as a novel series of chymase inhibitors. The structure-activity relationship studies of 1-oxacephems led to compounds 15, which exhibited 27 nM inhibition of human chymase and improvement of stability in human plasma (t 1/2 1.5 h).

MeSH terms

  • Cephalosporins / blood
  • Cephalosporins / chemical synthesis*
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacology
  • Chymases
  • Enzyme Stability
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Plasma / chemistry
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / blood
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Cephalosporins
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • Chymases

Associated data

  • PDB/1PJP