本文選題：三氟嗎啉 + 設計　； 參考：《南華大學》2016年碩士論文

【摘要】：目前,抑郁癥已經(jīng)被列為全球常見病中一種。據(jù)世界衛(wèi)生組織最新調(diào)查統(tǒng)計,全世界抑郁癥患者人數(shù)已達3.5億。抑郁癥與通常所見的情緒波動不同,病癥很復雜。中度或重度抑郁癥患者在學習、生活和工作中均表現(xiàn)出不佳的狀態(tài),常常會有自殺的念頭。在每年自殺人群中,因為抑郁癥死亡的人估計達100萬左右。當前,已經(jīng)上市的抗抑郁藥存在著耐受性差、起效慢、不良反應多等缺點,增加了自殺的危險性。因此,尋找作用效果好、起效時間快、耐受性好、安全性高的抗抑郁藥,具有重要的理論價值和實際意義。本文在課題組前期工作的基礎上,以三氟甲基苯丙酮為起始原料,設計合成了一系列新型三氟嗎啉類化合物。通過小鼠強迫游泳藥理實驗對其進行抗抑郁活性實驗評價,初步篩選出具有一定抗抑郁活性的化合物。本文研究內(nèi)容如下:1、設計了由三氟甲基苯丙酮為起始原料制備含三氟嗎啉鹽酸鹽的合成路線,合成了8個未見報道結(jié)構新穎的含三氟嗎啉鹽酸鹽化合物,目標化合物的結(jié)構經(jīng)過1H NMR、IR及MS確證。2、探索還原、酸化的最佳條件:還原加熱溫度為160℃,回流反應時間為12h。3、根據(jù)經(jīng)典的Porsolt法小鼠強迫游泳藥理實驗評價目標化合物的抗抑郁活性。小鼠強迫游泳藥理實驗顯示,化合物Vb和Vf小鼠強迫游泳不動時間分別為110.1±27.5s,107.1±29.4s,顯著低于空白組小鼠強迫游泳不動時間150.4±38.5s(P0.05)。因此,化合物Vb和Vf顯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 鹵27.5s (107.1 鹵29.4s) respectively, which was significantly lower than that of blank group (150.4 鹵38.5s) (P 0.05). Therefore, compounds VB and VF showed antidepressant activity.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R91;R914.5

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