Synthesis and structure-activity relationships of a new class of 1-oxacephem-based human chymase inhibitors

Bioorg Med Chem Lett. 2000 Nov 6;10(21):2397-401. doi: 10.1016/s0960-894x(00)00488-1.

Abstract

1-Oxacephem derivatives were synthesized and evaluated as a novel series of chymase inhibitors. Structure-activity relationship studies of 1-oxacephems led to compound 34, which exhibited 6 nM inhibition of human chymase and high selectivity for human chymase compared to other serine enzymes.

MeSH terms

  • Cephalosporins / chemical synthesis*
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacology
  • Chymases
  • Drug Design
  • Humans
  • Molecular Structure
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / metabolism
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Cephalosporins
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • Chymases