1,3-二氢-1,3-二氧-2H-异吲哚类衍生物的合成及抗新生血管生成活性研究  

Synthesis and Antiangiogenic Activities of 1,3-Dihydro-1,3-dioxo-2H-isoindole Derivatives

作　　者：邓勇[1] 钟裕国[2] 沈怡[2] 刘绍华[2] 

机构地区：[1]四川大学化工学院制药工程系 [2]四川大学华西药学院,成都610041

出　　处：《高等学校化学学报》2003年第2期260-264,共5页Chemical Journal of Chinese Universities

摘　　要：根据整合素 αvβ3 受体内源性配基 RGD三肽构效关系和作用机制 ,以沙利度胺为先导化合物 ,设计并合成了 5个未见文献报道的 5 -羧基 -1 ,3-二氢 -1 ,3-二氧 -2 H-异吲哚类衍生物 ,其结构经元素分析、红外光谱及核磁共振谱确证 .体外初步生物活性筛选实验结果表明 ,部分目标物对脐静脉血管内皮细胞株 ( ECV30 4 )增殖有显著抑制活性 .The growth of malignant tumors has been shown to be dependent on the evelopment of new blood vessels. Blocking tumor-induced angiogenesis is an efficiency strategy to prevent and cure cancer. It has been shown that the angiogenic process depends on vascular endothelial cell migration and invasion processes regulated by cell adhesion receptor. The integrin α vβ 3 is such a cell adhesion receptor. Recent studies show the integrin α vβ 3 and extracellular matrix can recognize each other through Arg-Gly-Asp(RGD) sequence, some peptides containing RGD sequence antagonists can inhibit embryonic neovascularization, tumor-induced angiogenesis, and tumor growth. According to the structure-activity relationships and antiangiogenic mechanism of RGD sequence, we use thalidomide as the leading structure to design and synthesize five 5-carboxy-1,3-dihydro-1,3-dioxo-2H-isoindole derivatives. All of them were first reported and their structures were confirmed by elementary analysis, IR and 1H NMR spectra. The results of preliminary antiangiogenic tests in vitro showed that most target compounds could inhibit ECV 304 proliferation. Moreover, it has been proved that the inhibition of endothelial cell proliferation was not the result of cytotoxic effect of target compounds.

关 键 词：RGD序列 沙利度胺 1 3-二氢-1 3-二氧-2H-异吲哚 衍生物 合成 抗新生血管生成活性 抗肿瘤药物 

分 类 号：R979.1[医药卫生—药品] R914.4[医药卫生—药学]