Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors

Yong-Yong Zheng; Lin Guo; Xue-Chu Zhen; Jian-Qi Li

doi:10.1016/j.ejmech.2012.04.030

Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors

Eur J Med Chem. 2012 Aug:54:123-36. doi: 10.1016/j.ejmech.2012.04.030. Epub 2012 Apr 30.

Authors

Yong-Yong Zheng¹, Lin Guo, Xue-Chu Zhen, Jian-Qi Li

Affiliation

¹ Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No.1 Road, Shanghai 200437, PR China.

PMID: 22608762
DOI: 10.1016/j.ejmech.2012.04.030

Abstract

A series of arylalkanol-piperidine derivatives was synthesized, and their triple reuptake inhibition and in vivo activities have been evaluated. Among them, compounds 2a, 2j, 2k, 2m and 2n exhibited high potency for 5-HT, NA and DA transporters. Optimized compounds 2j and 2m showed significant reduction of immobility time compared to that of vehicle in the mouse tail suspension test (TST) test at doses ranging from 10 to 50 mg/kg po, and were not generally motor stimulants at 50 mg/kg dose. In addition, compounds 2j and 2m displayed desirable pharmacokinetic properties in SD rats.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antidepressive Agents / chemistry*
Antidepressive Agents / metabolism
Antidepressive Agents / pharmacokinetics
Antidepressive Agents / pharmacology*
Chemistry Techniques, Synthetic
Male
Mice
Neurotransmitter Uptake Inhibitors / chemistry*
Neurotransmitter Uptake Inhibitors / metabolism
Neurotransmitter Uptake Inhibitors / pharmacokinetics
Neurotransmitter Uptake Inhibitors / pharmacology*
Piperidines / chemistry*
Piperidines / metabolism
Piperidines / pharmacokinetics
Piperidines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Biogenic Amine / metabolism

Substances

Antidepressive Agents
Neurotransmitter Uptake Inhibitors
Piperidines
Receptors, Biogenic Amine