N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2 antagonist

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1467-70. doi: 10.1016/s0960-894x(00)00260-2.

Abstract

The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its NK1 and NK2 receptor binding properties are reported. In addition the potent inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway bronchoconstriction in guinea pigs are demonstrated.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Asthmatic Agents / chemistry*
  • Anti-Asthmatic Agents / metabolism
  • Anti-Asthmatic Agents / pharmacology
  • Aza Compounds / pharmacology*
  • Benzamides / pharmacology*
  • Bronchoconstriction / drug effects
  • Drug Design
  • Guinea Pigs
  • Molecular Structure
  • Neurokinin A / analogs & derivatives*
  • Neurokinin A / pharmacology
  • Neurokinin-1 Receptor Antagonists*
  • Peptide Fragments / pharmacology
  • Receptors, Neurokinin-2 / antagonists & inhibitors*
  • Stereoisomerism
  • Substance P / pharmacology

Substances

  • Anti-Asthmatic Agents
  • Aza Compounds
  • Benzamides
  • N-(1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl)-N-methyl-3,5,-bis-trifluoromethyl-benzamide
  • Neurokinin-1 Receptor Antagonists
  • Peptide Fragments
  • Receptors, Neurokinin-2
  • neurokinin A (4-10), beta-Ala(8)-
  • Substance P
  • Neurokinin A