title: Synthesis, antidepressant activity, and toxicity of the erythro/threo racemates and optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl)hexan-1-ol.
abstract: The erythro/threo racemates and their four optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl)hexan-1-ol were synthesized and evaluated for their antidepressant activity, toxicity, and pharmacokinetics as novel triple multiple reuptake inhibitors of monoamine transmitters. The racemates and optical isomers were synthesized, respectively, through two different routes. Pharmacological data indicate that the erythro racemate (SIPI5357) that has better inhibitory activity and lower toxicity than the other racemate and optical isomers is worthy of further evaluation.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, China; State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai, 200437, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Weng
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianqi
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000441:Hexanols / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007536:Isomerism; D009281:Naphthalenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D000441:Hexanols; D009281:Naphthalenes; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C006737:1-benzylpiperazine; C036260:1-hexanol; C448759:1-methoxynaphthalene
keywords: antidepressant; erythro/threo racemate; optical isomer; triple reuptake inhibitor