Novel potent substance P and neurokinin A receptor antagonists. Conception, synthesis and biological evaluation of indolizine derivatives

Bioorg Med Chem. 2002 Sep;10(9):2905-12. doi: 10.1016/s0968-0896(02)00144-x.

Abstract

Exploration of SAR around dual NK(1)/NK(2) antagonist Cbz-Gly-Leu-Trp-OBzl(CF(3))(2) and its derivatives disclosed the essential requirements for more potent dual NK(1)/NK(2) binding. We report here the synthesis and the biological properties of a novel series of indolizine including pharmacophoric elements.

MeSH terms

  • Animals
  • Asthma / drug therapy
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Drug Design
  • Humans
  • Indolizines / chemical synthesis*
  • Indolizines / pharmacology
  • Neurokinin-1 Receptor Antagonists*
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology
  • Receptors, Neurokinin-2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Indolizines
  • Neurokinin-1 Receptor Antagonists
  • Oligopeptides
  • Receptors, Neurokinin-2
  • Calcium