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中文摘要：
目的设计合成4-取代苯胺基-1，2，3-苯并三嗪类化合物，并测定其体外抗增殖活性。方法以4-羟基-3-甲氧基苯甲腈为原料，经成醚、硝化、硝基还原制得中间体4-烷氧基-2-氨基-5-甲氧基苯甲腈，该中间体或邻氨基苯甲腈与不同取代的苯胺发生重氮化-偶合反应后再经环合、Dimroth重排反应得到目标化合物；采用MTr法，以瓦他拉尼（vatalanib）为阳性对照药，测试目标化合物对大鼠脑微血管内皮细胞（MVEC）的抗增殖活性。结果与结论合成了15个新化合物，其结构经IR、MS、1H—NMR谱确证；初步药理实验结果显示，2个目标化合物具有明显的抗MVEC增殖活性，其中，化合物7d的活性强于阳性对照，其GI50值为16．34μmol·L-1。
英文摘要：
Angiogenesis is required for the growth and metastasis of solid tumors. The direct inhibition of the VEGFRs＇ activity will result in the reduction of angiogenesis and the suppression of tumor growth. Based on the structures of the inhibitors of VEGFR vatalanib succinate （ PTK787 ） and vandetanib （ ZD6474 ）, a series of novel 4-substituted anilino-1,2,3-benzotriazines were designed and synthesized. The key intermediate 2- amino-5-methoxy-4-pentyloxybenzonitrile（4a） was prepared by etherification, nitration and nitro-reduction, then the intermediate 4a or 2-amino-benzonitrile （4b）reacted with different substituted anilines after a dia- zotization reaction, finally the target compounds were obtained by Dimroth rearrangement. 15 target com- pounds were synthesized and identified by IR, MS and 1H-NMR. The antiproliferative effects against murine microvascular endothelial cells （MVEC） of these compounds were tested using the MTT assay with vatalanib succinate as a positive control. Compound 7d （GIso = 16.34 μmol·L-1） showed more potent activity than vatalanib succinate （GI50= 38.15μmol· L-1） against MVEC. Preliminary structure-activity relationship was concluded from this research.
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