Monocharged inhibitors of mast cell tryptase derived from potent and selective dibasic inhibitors

Bioorg Med Chem Lett. 2001 Sep 3;11(17):2325-30. doi: 10.1016/s0960-894x(01)00444-9.

Abstract

Truncation of potent and selective dibasic inhibitors afforded monocharged inhibitors of human mast-cell tryptase. Using two classes of analogues as lead structures, several monocharged derivatives were identified with K(i) values ranging from 0.084 to 0.21 microM against the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / chemistry
  • Benzamidines / chemistry
  • Binding Sites
  • Biological Availability
  • Drug Design
  • Drug Evaluation, Preclinical
  • Guanidines / chemistry*
  • Guanidines / metabolism
  • Guanidines / pharmacology*
  • Humans
  • Molecular Mimicry
  • Piperazine
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Rats
  • Serine Endopeptidases / drug effects*
  • Serine Endopeptidases / metabolism
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / metabolism
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Tryptases
  • Urea

Substances

  • 3-(4-guanidinophenyl)-N-(2-phenylethyl)-3-((4-(3,3-diphenylpropylaminocarbonyl)piperazin-1-yl)carbonyl)propanamide
  • Benzamidines
  • Guanidines
  • Piperazines
  • Serine Proteinase Inhibitors
  • Piperazine
  • Urea
  • Arginine
  • Serine Endopeptidases
  • Tpsab1 protein, rat
  • Tpsb2 protein, rat
  • Tryptases
  • benzamidine