美西律衍生物的合成及其抗惊厥活性的研究

Synthesis and Anticonvulsant Activity of Mexiletine Derivatives

合成九个新的美西律(Mexiletine)氮取代苯甲基衍生物(Ⅳ_(a-i)),并和文献报道的部分化合物(Ⅳ_j和Ⅳ_k)一起进行了抗小鼠电休克惊厥试验,化合物Ⅳ_(a_d)有明显活性。测定了5个化合物的LD_(50)和ED_(50),化合物Ⅱ_a的LD_(50)为92.56mg/kg,ED_(50)为8.9mg/kg,其治疗指数为10.4,与美西律(9.3)相似。

Nine new Mexiletine derivatives were synthesized. These and other two compounds were tested for antielectrie convulsant acitvity in rats. LD_(50) and ED_(50) of compound Ⅰ(Mexiletine), Ⅱ_a, Ⅳ_a, Ⅳ_b and Ⅳ_d were determined. The LD_(50) and ED_(50) of Ⅱ_a are 92.56 mg/kg and 89 mg/kg respectively. Its theraputic index (10.4) is similar to that of Mexiletine (9.3).