吗氯贝胺衍生物的合成及其抗实验抑郁活性研究

Synthesis and Antidepressive Activity of Moclobemide Derivatives

合成出新的吗氯贝胺衍生物,对其抗抑郁活性进行了研究,以期寻找新的、潜在的活性强,副作用小的抗抑郁药物.本文以吗氯贝胺为先导化合物,以对氯苯甲酰氯为起始物,与溴乙胺氢溴酸盐反应,合成出4-氯-N-(2-溴乙基)苯甲酰胺;最后与吗啉衍生物进行N上的烃化反应,合成吗氯贝胺的衍生物.利用小鼠强迫游泳抗抑郁药理模型对所合成的化合物进行抗抑郁药理活性观察.目标化合物结构经1H NMR,IR和Ms确证.目标化合物3a具有一定的抗抑郁活性.

To synthesize the new moclobemide derivatives, research the antidepressant activity of moclobemide, filter the new antidepressant drugs of potential activity and side effects. This thesis is based on synthesized series morpholine derivative made in the eraly days. And then the bromoethylaminehydrobromide is synthetised by using ethanolamine as raw material and bromination. After this, 4-chloro-N-（ 2-bromo-ethyl ） -benzamide is prepared for Chlorobenzeneformyl chloride reaction;Finally, serial moclobemide derivative is synthetised by making alkylation in N with morpholine derivative. Synthetic reaction can gain high yield with less steps and simple conditions. Using the forced swim mice model of antidepressant pharmacology, the pharmacological effect s of antidepressant of the synthe- sized compounds were observed. The target compound is synthetised and its structure is proved by 1H NMR, IR and Ms. Target compounds have potent antidepressant activities,and are worth fur-ther development.