含氟吗啉衍生物的设计、合成及其抗抑郁活性研究

Design, Synthesis and Antidepressive Activity of Fluorine-containing Morpholinol Derivatives

目的合成6种含氟吗啉衍生物并对目标化合物进行抗抑郁活性筛选。方法以三氟甲基苯丙酮为起始原料,经过溴化、胺化、环合、还原、酸化反应合成6种新型含氟吗啉衍生物,采用小鼠强迫游泳模型,对目标化合物进行实验性抗抑郁药理活性研究。结果目标化合物物经1H-NMR、IR和MS分析确证。化合物Vb和Ve小鼠强迫游泳不动时间分别为(110.1±27.5)s和(107.1±29.4)s,显著低于空白对照组[(150.4±38.5)s](P<0.05)。结论该合成路线反应条件温和、操作简便,目标化合物Vb和Ve显示出一定的抗抑郁活性。

OBJECTIVE To synthesize 6 kinds of fluorine-containing morpholinol derivatives and to explore their antidepressant activity. METHODS The target compounds were synthesized from trifluoromethyl substituted propiophenone via bromination, amination, cyclization, reduction, acidification. The antidepressant activity of all synthesized compounds were evaluated by the forced swimming test in mice. RESULTS The structure of target compounds were identified by 1H-NMR, IR and MS. The immobility time of compound Vb and Ve were significantly shorter than the blank control group（P〈0.05）. CONCLUSION This synthetic process is simple and easy to control. Compound Vb and Ve have shown some antidepressant activities.