Potent and orally bioavailable non-peptide antagonists at the human bradykinin B(1) receptor based on a 2-alkylamino-5-sulfamoylbenzamide core

J Med Chem. 2004 Sep 9;47(19):4642-4. doi: 10.1021/jm049747g.

Abstract

The bradykinin B(1) receptor is rapidly induced after inflammation or tissue trauma and appears to play an important role in the maintenance of hyperalgesia in inflammatory conditions. Here, we describe the optimization process to identify novel, potent non-peptide human B(1) receptor antagonists based on a 2-alkylamino-5-sulfamoylbenzamide core. Optimized derivatives are selective, functional B(1) antagonists with low nanomolar affinity and exhibit oral bioavailability in animals.

Publication types

  • Letter

MeSH terms

  • Administration, Oral
  • Amines / chemistry
  • Amino Acids / chemistry
  • Biological Availability
  • Bradykinin B1 Receptor Antagonists*
  • Carboxylic Acids / chemistry
  • Humans
  • Molecular Structure
  • Peptides / administration & dosage
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology
  • ortho-Aminobenzoates / administration & dosage
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacokinetics*
  • ortho-Aminobenzoates / pharmacology

Substances

  • Amines
  • Amino Acids
  • Bradykinin B1 Receptor Antagonists
  • Carboxylic Acids
  • Peptides
  • ortho-Aminobenzoates
  • anthranilamide