Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056)

Zhijie Weng; Jianqi Li

doi:10.1016/j.bmcl.2009.11.108

Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056)

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1256-9. doi: 10.1016/j.bmcl.2009.11.108. Epub 2009 Nov 27.

Authors

Zhijie Weng¹, Jianqi Li

Affiliation

¹ Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan Road, Shanghai 200437, PR China.

PMID: 20022503
DOI: 10.1016/j.bmcl.2009.11.108

Abstract

Four optical isomers of SIPI5056 were synthesized and evaluated for their antidepressant activities and acute toxicities as novel multiple reuptake inhibitors of monoamine transmitters. Chiral alanines were used as educts to prepare their respective target compounds in nine steps. Pharmacological results showed that the (1R,2S)-SIPI5056 isomer has higher inhibitory activity and lower toxicity than other three isomers and is worthy of further development.

Publication types

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

MeSH terms

Animals
Antidepressive Agents / chemical synthesis*
Antidepressive Agents / therapeutic use
Antidepressive Agents / toxicity
Cerebral Cortex / drug effects
Cerebral Cortex / metabolism
Lethal Dose 50
Mice
Naphthalenes / chemical synthesis*
Naphthalenes / therapeutic use
Naphthalenes / toxicity
Piperazines / chemical synthesis*
Piperazines / therapeutic use
Piperazines / toxicity
Propanols / chemical synthesis*
Propanols / therapeutic use
Propanols / toxicity
Rats
Stereoisomerism
Synaptosomes / drug effects
Synaptosomes / metabolism

Substances

Antidepressive Agents
Naphthalenes
Piperazines
Propanols