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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。
Objective To study the synthesis and antidepressant activities of aralkanols and piperazines. Methods The piperazines were protected by formyl group and alkylated with the corresponding halogenated arenes to prepare aralkyl piperazines, which were then reduced by sodium borohydride to give the target compounds of aralkanol piperazines. The inhibitory activity of the target compound on the reuptake of monoamine neurotransmitters was determined by in vitro experiments and the anti-depressant activity of compound III2 in vivo was studied by forced swimming test in mice and tail-suspension test in mice. Results A total of 32 novel compounds were synthesized and their structures were confirmed by MS and 1H-NMR. The target compounds Ⅱ5, Ⅲ2, Ⅲ3, Ⅲ5 and Ⅲ15 had higher inhibitory activity on the reuptake of serotonin (5-HT) and norepinephrine (NA), of which compound Ⅲ2 had the best effect. In vivo studies also showed that compound III2 has good antidepressant activity in mice. Conclusion Compound Ⅲ 2 shows good antidepressant activity in vitro and in vivo, and has the value of further development.