目的 合成N-(2,3-二甲基-2H-吲唑-6-基)-2-甲基嘧啶二胺衍生物,测试所合成化合物的体外抗肿瘤活性。方法 在已上市的多靶点小分子抗肿瘤药pazopanib的构效关系基础上,采用基于片段的药物设计方法设计合成目标化合物;采用四氮唑盐(MTT)法测试所合成化合物的体外抗肿瘤活性。结果 合成了14个N-(2,3-二甲基-2H-吲唑-6-基)-2-甲基嘧啶二胺衍生物,目标化合物的结构经¹H-NMR、MS及元素分析确证。结论 大多数合成的化合物表现出一定的抗肿瘤活性,其中化合物B1和B2的抗肿瘤活性优于阳性对照。

To synthesize N-(2,3-dimethyl-2H-indazol-6-yl)-2-methylpyrimidinediamine derivatives and determine their antitumor activities in vitro. METHODS Basing on the marketed multi-target antitumor agent, pazopanib, the substances were designed and synthesized according to the principle of fragment-based drug discovery. The antitumor activities in vitro of the synthesized compounds were evaluated by MTT method. RESULTS Fourteen derivatives were synthesized. Their structures were identified by ¹H-NMR, MS and elemental analysis. CONCLUSION It is shown that most of the synthesized compounds have antitumor activities, among which compound B1 and B2 show better antitumor activity than the positive control.