Design of novel multiple-acting ligands towards SERT and 5-HT2C receptors

Bioorg Med Chem Lett. 2014 May 1;24(9):2118-22. doi: 10.1016/j.bmcl.2014.03.043. Epub 2014 Mar 24.

Abstract

This Letter describes our attempts to elaborate dually acting compounds possessing serotonin re-uptake transporter inhibitor and serotonin 5-HT2C receptor antagonist properties. A novel series of 1,3-diphenylureas and N-phenylbenzamides have thus been prepared and evaluated. Based on its in vitro and in vivo activities, as well as pharmacokinetic profile, compound 16a was identified as a lead compound. The synthesis and structure-activity relationship of this series of compounds is presented herein.

Keywords: 5-HT(2C) antagonist; Designed multiple ligands; SERT inhibitor.

MeSH terms

  • Animals
  • Benzamides / chemistry*
  • Benzamides / pharmacokinetics
  • Benzamides / pharmacology*
  • Carbanilides / chemistry*
  • Carbanilides / pharmacokinetics
  • Carbanilides / pharmacology*
  • Drug Design
  • Humans
  • Ligands
  • Mice
  • Models, Molecular
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin 5-HT2 Receptor Antagonists / chemistry*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacokinetics
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Carbanilides
  • Ligands
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Antagonists