Synthesis and antidepressant-like activity of novel alkoxy-piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Bioorg Med Chem Lett. 2019 Dec 15;29(24):126769. doi: 10.1016/j.bmcl.2019.126769. Epub 2019 Oct 28.

Abstract

A series of novel alkoxy-piperidine derivatives were synthesized and evaluated for their serotonin reuptake inhibitory and binding affinities for 5-HT1A/5-HT7 receptors. In vivo antidepressant activities of the selective compounds were explored using the forced swimming test (FST) and tail suspension test (TST) in mice. The results showed that compounds 7a (reuptake inhibition (RUI), IC50 = 177 nM; 5-HT1A, Ki = 12 nM; 5-HT7, Ki = 25 nM) and 15g (RUI, IC50 = 85 nM; 5-HT1A, Ki = 17 nM; 5-HT7, Ki = 35 nM) were potential antidepressant agents in animal behavioral models with high 5-HT1A/5-HT7 receptor affinities and moderate serotonin reuptake inhibition, and good metabolic stability in vitro.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Humans
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*

Substances

  • Antidepressive Agents
  • Piperidines
  • Serotonin Uptake Inhibitors