Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3434-9. doi: 10.1016/j.bmcl.2006.04.013. Epub 2006 Apr 27.

Abstract

Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P(2) binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Haplorhini
  • Humans
  • Mast Cells / drug effects*
  • Mast Cells / enzymology
  • Mice
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology
  • Serine Endopeptidases / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tryptases

Substances

  • Enzyme Inhibitors
  • Oxadiazoles
  • Tpsb2 protein, mouse
  • Serine Endopeptidases
  • Tpsab1 protein, mouse
  • Tryptases