Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056).
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.
Weng
Zhijie
Z
Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan Road, Shanghai 200437, PR China.
Li
Jianqi
J
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007928:Lethal Dose 50; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D010879:Piperazines / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D020005:Propanols / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D009281:Naphthalenes; D010879:Piperazines; D020005:Propanols