Design, synthesis, and systematic evaluation of 4-arylpiperazine- and 4-benzylpiperidine napthyl ethers as inhibitors of monoamine neurotransmitters reuptake

Bioorg Med Chem. 2018 Nov 1;26(20):5538-5546. doi: 10.1016/j.bmc.2018.09.033. Epub 2018 Sep 26.

Abstract

Two series of 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers were designed based on structure-activity relationship (SAR) and docking model of reported monoamine neurotransmitters reuptake inhibitors. The compounds were synthesized in 3-simple steps and their biological activities were evaluated. Several compounds were proven to be potent inhibitors of serotonin and norepinephrine reuptake. Computer docking was performed to study the interaction of the most potent compound 35 with human serotonin transporter. The results of the analyses suggest that 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers might be promising antidepressants worthy of further studies.

Keywords: 4-Arylpiperazine; 4-Benzylpiperidine; Depression; Docking; Naphthyl ether; Norepinephrine reuptake inhibitor; Serotonin reuptake inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology
  • Drug Design
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Norepinephrine / metabolism
  • Piperazine / analogs & derivatives*
  • Piperazine / pharmacology*
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Serotonin and Noradrenaline Reuptake Inhibitors / chemistry*
  • Serotonin and Noradrenaline Reuptake Inhibitors / pharmacology*

Substances

  • Antidepressive Agents
  • Piperidines
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Piperazine
  • Serotonin
  • 1-benzylpiperidine
  • Norepinephrine