三氟吗啉衍生物分子设计、合成及其抗抑郁活性

发布时间：2018-06-10 01:44

本文选题：三氟吗啉 + 设计　；参考：《南华大学》2016年硕士论文

【摘要】：目前,抑郁症已经被列为全球常见病中一种。据世界卫生组织最新调查统计,全世界抑郁症患者人数已达3.5亿。抑郁症与通常所见的情绪波动不同,病症很复杂。中度或重度抑郁症患者在学习、生活和工作中均表现出不佳的状态,常常会有自杀的念头。在每年自杀人群中,因为抑郁症死亡的人估计达100万左右。当前,已经上市的抗抑郁药存在着耐受性差、起效慢、不良反应多等缺点,增加了自杀的危险性。因此,寻找作用效果好、起效时间快、耐受性好、安全性高的抗抑郁药,具有重要的理论价值和实际意义。本文在课题组前期工作的基础上,以三氟甲基苯丙酮为起始原料,设计合成了一系列新型三氟吗啉类化合物。通过小鼠强迫游泳药理实验对其进行抗抑郁活性实验评价,初步筛选出具有一定抗抑郁活性的化合物。本文研究内容如下:1、设计了由三氟甲基苯丙酮为起始原料制备含三氟吗啉盐酸盐的合成路线,合成了8个未见报道结构新颖的含三氟吗啉盐酸盐化合物,目标化合物的结构经过1H NMR、IR及MS确证。2、探索还原、酸化的最佳条件:还原加热温度为160℃,回流反应时间为12h。3、根据经典的Porsolt法小鼠强迫游泳药理实验评价目标化合物的抗抑郁活性。小鼠强迫游泳药理实验显示,化合物Vb和Vf小鼠强迫游泳不动时间分别为110.1±27.5s,107.1±29.4s,显著低于空白组小鼠强迫游泳不动时间150.4±38.5s(P0.05)。因此,化合物Vb和Vf显示出一定的抗抑郁活性。
[Abstract]:At present, depression has been listed as a common disease in the world. According to the latest survey by the World Health Organization, the number of depression patients in the world has reached 350 million. Depression is different from the usual mood swings, and the disease is complex. People with moderate or severe depression show poor learning, life, and work, and often have suicidal thoughts. Depression kills an estimated 1 million people a year among suicides. At present, antidepressants that have been put on the market have some disadvantages, such as poor tolerance, slow onset and many adverse reactions, which increase the risk of suicide. Therefore, it is of great theoretical and practical significance to find antidepressants with good effect, fast onset time, good tolerance and high safety. In this paper, a series of new trifluoromorpholine compounds were designed and synthesized from trifluoromethylphenylacetone based on the previous work of our research group. The antidepressant activity of mice was evaluated by forced swimming pharmacological experiment, and the compounds with certain antidepressant activity were preliminarily selected. The main contents of this paper are as follows: 1. The synthesis route of trifluoromethylmorpholine hydrochloride from trifluoromethylphenylacetone was designed, and eight novel trifluoromorpholine hydrochloride compounds were synthesized. The structure of the target compound was confirmed by 1H-NMR-IR and Ms. The reflux reaction time was 12 h. 3. The antidepressant activity of the target compound was evaluated according to the classical porsolt method. The pharmacological tests of forced swimming in mice showed that the immobility time of compound VB and Vf was 110.1 卤27.5s (107.1 卤29.4s) respectively, which was significantly lower than that of blank group (150.4 卤38.5s) (P 0.05). Therefore, compounds VB and VF showed antidepressant activity.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R91;R914.5

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