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

• 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
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.04.030

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.