Design and synthesis of potential dual NK(1)/NK(3) receptor antagonists

Bioorg Med Chem Lett. 2014 Jan 15;24(2):510-4. doi: 10.1016/j.bmcl.2013.12.033. Epub 2013 Dec 15.

Abstract

The tachykinin NK1 and NK3 receptors are a novel drug target for schizophrenia in order to treat not only the positive and cognitive symptoms, but also the associated co-morbid depression and sleep disturbances associated with the disease. A novel class of peptidomimetic derivatives based on a versatile phenylglycine central core was synthesized and tested in vitro as dual NK1/NK3 receptor antagonists. From this series emerged compounds with good NK1 receptor affinity, although only modest dual NK1/NK3 receptor affinity was observed with one of these analogs.

Keywords: NK(1)/NK(3) receptor antagonists; Neurokinin receptors; Peptidomimetic; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / metabolism
  • Drug Design*
  • Neurokinin-1 Receptor Antagonists / chemical synthesis*
  • Neurokinin-1 Receptor Antagonists / metabolism
  • Receptors, Neurokinin-1* / metabolism
  • Receptors, Neurokinin-3 / antagonists & inhibitors*
  • Receptors, Neurokinin-3 / metabolism
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-3