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

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 reduc...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2012-08, Vol.54, p.123-136
Main Authors: Zheng, Yong-Yong, Guo, Lin, Zhen, Xue-Chu, Li, Jian-Qi
Format: Article
Language:English
Subjects:
Animals
Antidepressant
Antidepressive Agents - chemistry
Antidepressive Agents - metabolism
Antidepressive Agents - pharmacokinetics
Antidepressive Agents - pharmacology
Arylalkanol-piperidine derivatives
Biological and medical sciences
Chemistry Techniques, Synthetic
Male
Medical sciences
Mice
Miscellaneous
Neurotransmitter Uptake Inhibitors - chemistry
Neurotransmitter Uptake Inhibitors - metabolism
Neurotransmitter Uptake Inhibitors - pharmacokinetics
Neurotransmitter Uptake Inhibitors - pharmacology
Pharmacology. Drug treatments
Piperidines - chemistry
Piperidines - metabolism
Piperidines - pharmacokinetics
Piperidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Biogenic Amine - metabolism
Triple reuptake inhibitor
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Summary: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. [Display omitted] ► A series of arylalkanol-piperidine derivatives (2a–y) were synthesized. ► Synthesized compounds were tested for triple reuptake inhibition and antidepressant activities. ► 5 compounds exhibited high potency for 5-HT, NA and DA transporters. ► Some compounds showed antidepressant activities in TST and displayed desirable pharmacokinetic properties.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2012.04.030