Discovery of a cyclopentylamine as an orally active dual NK1 receptor antagonist-serotonin reuptake transporter inhibitor

Bioorg Med Chem Lett. 2014 Mar 15;24(6):1611-4. doi: 10.1016/j.bmcl.2014.01.036. Epub 2014 Jan 27.

Abstract

Cyclopentylamine 4 was identified as a potent dual NK1R antagonist-SERT inhibitor. This compound demonstrated significant oral activity in the gerbil forced swimming test, suggesting that dual NK1R antagonists-SERT inhibitors may be useful in treating depression disorders.

Keywords: Dual NK(1) receptor antagonists–serotonin reuptake transporter inhibitor; NK(1) receptor (NK(1)R) antagonist; Serotonin reuptake transporter (SERT) inhibitor.

MeSH terms

  • Administration, Oral
  • Animals
  • Crystallography, X-Ray
  • Cyclopentanes / chemical synthesis
  • Cyclopentanes / chemistry*
  • Cyclopentanes / pharmacology
  • Drug Evaluation, Preclinical
  • Gerbillinae
  • Humans
  • Molecular Conformation
  • Motor Activity / drug effects
  • Neurokinin-1 Receptor Antagonists / chemistry*
  • Neurokinin-1 Receptor Antagonists / metabolism
  • Neurokinin-1 Receptor Antagonists / pharmacology
  • Protein Binding
  • Receptors, Neurokinin-1 / chemistry*
  • Receptors, Neurokinin-1 / metabolism
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis
  • Selective Serotonin Reuptake Inhibitors / chemistry*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • Cyclopentanes
  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-1
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • cyclopentylamine