美西律衍生物的合成及其抗惊厥活性

Synthesis and Anticonvulsant Activity of Mexiletine Derivatives

以美西律为先导化合物,合成了5个美西律的氮酰化衍生物Ⅲa-e和3个肟醚类化合物Ⅳa-c。氮酰化物用酰氯法合成,环状的酰亚胺衍生物以相应的二元酸酐为酰化剂,经单酰胺中间体,在适当的催化剂存在下脱水环合。肟醚类化合物采用酮肟钠盐与相应的氯苄反应制备。所合成的化合物经小鼠抗电惊厥试验,N-(1-甲基-2-(2,6-二甲基苯氧基)乙基)丁酰亚胺有一定抗惊厥活性,其它化合物无活性。

Eight new N-substituted amides Ⅲ a-e and oxime ethers Ⅳ a-c of Mexiletine were prepared. Mexiletine was acytylated by acyl chloride to from Ⅲ a-c. Cyclic imides Ⅲ d and Ⅲ e were synthesized at the presence of proper catalyst for dehydration and cyclization, through the intermediates of monoamide of bicarboxylic acid Ⅴ a and Ⅴ b. These new synthesized compounds were tested for antielectric convulsant activity in rats. They all have no antivonvulsant activity except Ⅲ d.