Identification of a new series of non-peptidic NK3 receptor antagonists

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1498-501. doi: 10.1016/j.bmcl.2010.12.135. Epub 2011 Jan 13.

Abstract

The identification and structure-activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK(3) receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK(3) receptor and brain exposure, leading to activity in vivo in the senktide-induced hypoactivity model in gerbils.

MeSH terms

  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Amides* / pharmacology
  • Animals
  • Carboxylic Acids* / chemical synthesis
  • Carboxylic Acids* / chemistry
  • Carboxylic Acids* / pharmacology
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Disease Models, Animal
  • Gerbillinae
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology
  • Receptors, Neurokinin-3 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Amides
  • Carboxylic Acids
  • Cyclopropanes
  • Peptides
  • Receptors, Neurokinin-3