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根据已知的激酶变构抑制剂与其靶点激酶的X射线共晶结构,设计了一系列以吡啶联异噁唑为中心结构的潜在激酶变构抑制剂.以2-甲基-5-硝基-3-吡啶甲酸甲酯为原料,通过形成酰胺、磺酰胺和连接嘧啶片段等衍生化手段合成了21个新的吡啶联异噁唑类化合物,其结构经1H NMR,13C NMR和MS确证.采用噻唑蓝(MTT)法测试了所合成化合物的体外抗肿瘤活性,初步测试结果表明该类化合物对肿瘤细胞的增长具有显著的抑制作用.
According to the X-ray eutectic structure of known kinase allosteric inhibitors and their target kinases, a series of potential allosteric inhibitors of kinases with pyridine isoxazole as central structure were designed. Methyl-3-pyridinecarboxylate as raw materials, 21 novel pyridylisoxazoles were synthesized via derivatization of amides, sulfonamides and pyrimidine fragments, and their structures were confirmed by 1H NMR, 13C NMR and MS The in vitro antitumor activity of the synthesized compounds was tested by MTT assay, and the preliminary test results showed that these compounds have significant inhibitory effect on the growth of tumor cells.