芳烷醇哌嗪类化合物的合成及抗抑郁活性  

Synthesis and antidepressant activities of aryl alkanol piperazine derivatives

作　　者：李建其[1] 黄丽瑛[1] 董文心[1] 翁志洁[1] 金华[1] 倪湘莲[1] 张绍静[1] 黄朝峰[1] 顾丰华[1] 

机构地区：[1]上海医药工业研究院,上海200040

出　　处：《中国药物化学杂志》2006年第5期270-276,共7页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划(863计划)项目(2002AA2Z3140)

摘　　要：目的研究芳烷醇哌嗪类化合物的合成及抗抑郁活性。方法哌嗪经甲酰基保护后,与相应的卤代芳烃进行烷基化反应制备芳烷酮哌嗪化合物,再经钠硼氢还原制得芳烷醇哌嗪类目标化合物。通过体外实验测定目标化合物对单胺递质再摄取的抑制活性,并通过小鼠强迫游泳实验和小鼠尾悬挂实验对化合物Ⅲ2进行体内抗抑郁活性研究。结果合成32个未见文献报道的新化合物,其结构经MS和1H-NMR谱确证。目标化合物Ⅱ5、Ⅲ2、Ⅲ3、Ⅲ5和Ⅲ15对5-羟色胺(5-HT)和去甲肾上腺素(NA)的再摄取均具有较高的抑制活性,其中,化合物Ⅲ2的作用最佳。体内研究结果也显示化合物Ⅲ2在小鼠体内具有很好的抗抑郁活性。结论化合物Ⅲ2显示出很好的体内外抗抑郁活性,具有深入开发的价值。Aim To study the synthesis and antidepressant activities of aryl alkanol piperazine derivatives. Methods The nitrogen atom of one side of piperazine ring was protected by formyl group firstly, then the unprotected nitrogen atom was alkylated to prepare the aralkyl-ketone piperazine derivatives, which were reduced to prepare aryl alkanol piperazine derivatives by NaBH4. The serotonin （5-HT） and noradrenaline （NA） reuptake inhibiting activities of the title compounds were studied in vitro, the antidepressant activities of compound Ⅲ2 were studied in vivo by forced swimming test （FST） and tail suspension test （TST） of mice. Results 32 new compounds were synthesized and their structure were confirmed by MS and ^1H-NMR. Compounds Ⅱs, Ⅲ2,Ⅲ3,Ⅲ5 and Ⅲ15 showed strong 5-HT and NA reuptake inhibiting activities in vitro. Compound Ⅲ2 also showed obvious antidepressant activities in vivo. Conclusion Compound Ⅲ2 has potent antidepressant activities and is worth further development.

关 键 词：药物化学 化合物制备 化学合成 芳烷醇哌嗪类化合物 抗抑郁活性 

分 类 号：R914[医药卫生—药物化学]