N-取代邻苯二甲酰亚胺类衍生物的设计、合成及活性评价

Design,Synthesis and Activity Evaluation of N-Substituted Phthalimide Derivatives

结合中药脱皮马勃中分离得到的3,5-二羟基邻苯二甲酰亚胺和邻苯二甲酰亚胺类化合物的结构设计合成了一系列N-取代-3,5-二甲氧基邻苯二甲酰亚胺及N-取代-3,5-二羟基邻苯二甲酰亚胺类衍生物,其结构经1H NMR,13C NMR和MS分析确证.选取人肺腺癌细胞A549及人脐静脉血管内皮细胞HUEVC为测试细胞株,评价了所合成化合物的体外抗肿瘤及抗血管生成活性,结果表明,部分化合物表现出一定的活性.

One novel compound 3,5-dimethoxy phthalimide had been isolated from Lasiosphaerafenzlii Reich. The compound exhibited definite antioxidant activity. Meanwhile it was reported that many compounds with the skeleton of phthalimide displayed many bioactivities such as anti-angiogenesis, anti-inflammatory, immune regulation and anti-tumor and so on. On the comprehensive review of above evidences, a series of N-substitu- ted-3,5-dimethoxy phthalimide derivatives and N-substituted-3,5-dihydroxy phthalimide derivatives were de- signed and synthesized. Those compounds were synthesized by the multi-step reaction, 3,5-dimethoxybenzoic acid was used as a starting material, and sequentially generates the phthalic anhydride and phthalimide, then reacted with a series of halogenated hydrocarbons, and stripped of methyl to obtain the target compounds. Thirty-one new compounds were synthesized, and the structures were characterized by 1H NMR, 13C NMR and MS techniques. Their anti-tumor and anti-angiogenesis activities against A549 and HUVEC cell line in vitro were tested. Some compounds showed a certain activity.