Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones

Bioorg Med Chem Lett. 2001 Jul 9;11(13):1691-4. doi: 10.1016/s0960-894x(01)00264-5.

Abstract

The present work demonstrates that the 1,3-diazetidine-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha-chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase.

MeSH terms

  • Azetidines / chemistry
  • Azetidines / pharmacology*
  • Cathepsin G
  • Cathepsins / antagonists & inhibitors*
  • Chymotrypsin / antagonists & inhibitors*
  • Humans
  • Leukocyte Elastase / antagonists & inhibitors
  • Serine Endopeptidases
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology*
  • Substrate Specificity

Substances

  • Azetidines
  • Serine Proteinase Inhibitors
  • Cathepsins
  • Serine Endopeptidases
  • Chymotrypsin
  • alpha-chymotrypsin
  • CTSG protein, human
  • Cathepsin G
  • Leukocyte Elastase