Synthesis And Antidepressant Activity Of Moclobemide Derivatives

Moclobemide is a monoamine inhibitors with selectivity, features a high degreeof reversibility, its main role is the selective inhibition of monoamine oxidase ADuplicate absorption,5-serotonin and norepinephrineadjusting the amount of thenormal level. Clinical applications show that moclobemide for depression efficacy,side effects, for all ages, after stopping monoamine oxidase activity and rapidrecoveryThe Topic as moclobemide lead compounds by morpholine ring structuraltransformation, modification of the structure of the lead compound to synthesize aseries of new compounds synthesized in this study four kinds of moclobemidederivatives. The research group through the further pharmacologically active filter, thetarget compound found that the compound N-[2-(3,5-dimethyl yl-2-(3-fluoro-phenyl) morpholinyl) ethyl chlorobenzamide (3a) has a good antidepressantactivity, it is worth further study.The main subject of research work are as follows:(1) In the existing drugs moclobemide lead compounds, through thetransformation of the structure of a morpholine ring, with the reaction of4-chloro-N-(2-bromo-ethyl)-benzamide Synthesis of4differentthe moclobemide aminederivatives, by IR,1H NMR and MS its structural characterization.(2) The study on the affect of the product yield by the ratio of reactants, reactiontemperature, reaction time and etc, to optimize the reaction conditions.(3) Mouse forced swimming method and tail suspension test for antidepressantactivity drug experimental model, the synthesis of four target compounds bioassayfound the compounds3a has a good antidepressant activity. Further the mechanisms3a pair of monoamine oxidase A inhibition rate: in the hippocampus,23.03%, thehypothalamus16.54%,17.03%prefrontal. In the hippocampus of monoamine oxidaseB inhibition rate:3.20%,0.79%in the hypothalamus, prefrontal2.44%, experimentsshow that compounds3a monoamine oxidase A has a certain degree of inhibition.