Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Bioorg Med Chem Lett. 2019 Dec 1;29(23):126703. doi: 10.1016/j.bmcl.2019.126703. Epub 2019 Sep 15.

Abstract

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

Keywords: 5-HT(1A) receptor; 5-HT(7) receptor; Antidepressant; Serotonin reuptake inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Humans
  • Piperazine / pharmacology
  • Piperazine / therapeutic use*
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Antidepressive Agents
  • Piperidines
  • Serotonin Uptake Inhibitors
  • Piperazine
  • piperidine