1（3H）-异苯并呋喃酮-Δ^3-乙酰胺类化合物的合成及其抗惊厥活性

Synthesis and anticonvulsant activities of isobenzofuran-1(3H)-one-Δ3-acetylamines

目的寻找具有抗惊厥活性的1(3H)-异苯并呋喃酮-Δ3-乙酰胺类化合物。方法以邻苯二甲酸酐为原料,先制备酞乙酸,再依次与氯化亚砜、胺反应合成9个(Z)-1(3H)-异苯并呋喃酮-Δ3-乙酰胺类化合物;以氯乙酸为起始原料,依次与氯化亚砜、胺、三苯基膦反应制得季磷盐,再与邻苯二甲酸酐经Wittig反应又合成9个(E)-1(3H)-异苯并呋喃酮-Δ3-乙酰胺类化合物。所有目标化合物的结构均经IR和1H-NMR确证。采用最大电休克发作实验(MES)对目标化合物进行抗惊厥活性筛选。结果合成了18个未见文献报道的新化合物。5e、5h和5i的抗惊厥活性ED50值分别为155.6、184.6和170.4 mg.kg-1。结论E型异构体较Z型异构体具有较好的抗惊厥活性,其构效关系和药理作用机制值得进一步研究。

Aim To search anticonvulsant activities of isobenzofuran-1 （3H）-one-Δ^3-acetylamines. Methods Nine Z-isomers were synthesized by treating phthalic anhydride with thionyl chloride and amines in turn. And nine E-isomers were synthesized by treating phthalic anhydride with quaternary phosphonium salts. All compounds were determined by IR and ^1H-NMR. Their anticonvulsant activities were tested by maximal electroshock seizure（MgS）experiment. Results Eighteen new compounds were synthesized, 5e, 5h and 5i have activities, their ED50 values are 155.6, 184.6 and 170.4 mg· kg^- 1 respectively. Conclusion E-isomers were more potent than Z-isomers. It is worthy of further study on the structure activity relationship and pharmacological mechanism.