Arylpiperazine-containing pyrimidine 4-carboxamide derivatives targeting serotonin 5-HT(2A), 5-HT(2C), and the serotonin transporter as a potential antidepressant

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6439-42. doi: 10.1016/j.bmcl.2010.09.081. Epub 2010 Sep 19.

Abstract

Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Animals
  • Antidepressive Agents, Second-Generation / chemistry
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Mice
  • Piperazines / chemistry*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Receptor, Serotonin, 5-HT2A / drug effects*
  • Receptor, Serotonin, 5-HT2C / drug effects*
  • Serotonin Plasma Membrane Transport Proteins / drug effects*

Substances

  • Amides
  • Antidepressive Agents, Second-Generation
  • Piperazines
  • Pyrimidines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Serotonin Plasma Membrane Transport Proteins