3-甲基-5-苯基-2-芳基吗啉盐酸盐合成及其抗实验性抑郁活性

Synthesis and Antidepressant Activity of 2-Aryl-3-methyl-5-phenylmorpholine Hydrochloride

以2-芳基吗啉为先导化合物,利用外消旋化合物2-苯基-2-氨基-1-乙醇分别与2-溴-3′-氯苯丙酮、2-溴苯丙酮、6-甲氧基-2-(2′-溴丙酰基)萘、2-溴-4′-甲氧基苯丙酮反应,合成了吗啉环上5位含苯基的新型2-芳基吗啉类化合物3-甲基-5-苯基-2-(3′-氯苯基)吗啉,3-甲基-2,5-二苯基吗啉,3-甲基-5-苯基-2-(6′-甲氧基-2′-萘基)吗啉,3-甲基-5-苯基-2-(4-甲氧基苯基)吗啉,经氯化氢酸化后得到其盐酸盐,总收率分别为52.4%、55.3%、47.6%和51.2%,目标化合物结构经IR、1H NMR、MS测试技术确证。参照Porsolt法,小鼠强迫游泳药理实验模型,观察所合成的化合物抗小鼠实验性抑郁活性。结果表明,化合物4a对小鼠强迫游泳中静止时间为(128.8±20.1)s,低于空白对照组的(152.2±26.8)s。

2-Aryl-3-methyl-5-phenylmorpholine compounds were synthesized via the reactions of 2-amino-2- phenyl-1 -alcohol with 2-bromo-3-chloropropiophenone, 2-bromopropiophenone, 6-methoxy-2-（ 2-bromopropio- nyl） naphthalene or 2-bromo-4-methoxypropiophenone respectively, followed by their reactions with 2-aryl-3- methyl-5-phenyl-2-morpholine and hydrochloride to obtain the hydrochloride salts with yields of 52, 4%, 55.3% , 47.6% , and 51.2% , respectively. The structures of the target compounds were confirmed by means of IR, ^1H NMR and MS spectra. Their antidepressant activities were tested with mice forced swimming test. The results showed that the mice that were administered with the intermediate 4a had shorter immobility time than the blank control mice in forced swimming test.