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目的设计合成新型2-吲哚酮类c-Met激酶抑制剂。方法以c-Met激酶抑制剂SU11274为先导化合物,利用生物电子等排原理设计出系列2-吲哚酮类衍生物。以2-吲哚酮为起始原料,先后经历与氯磺酸的氯磺酰化、与3的磺酰胺化、与6a~6h,7a~7h和4a~4b的缩合反应制得目标产物10a~10r,并测定它们对c-Met激酶和MCF-7细胞增殖的抑制活性。结果与结论成功合成了设计的18个2-吲哚酮类化合物,产物结构经1H NMR和ESI-MS确证。部分化合物显示出一定的c-Met激酶和MCF-7细胞增殖抑制活性。对目标产物进行了初步构效关系分析,为该类化合物进一步的结构优化奠定了基础。
Aim To design and synthesize novel 2-indolones c-Met kinase inhibitors. Methods The c-Met kinase inhibitor SU11274 was used as the lead compound to design a series of 2-indolone derivatives using bioisosterism. Starting from 2-indolone, it undergoes the chlorosulfonylation with chlorosulfonic acid, the sulfonylation with 3, and the condensation reaction with 6a ~ 6h, 7a ~ 7h and 4a ~ 4b to obtain the target product 10a ~ 10r and assayed their inhibitory activity on the proliferation of c-Met kinase and MCF-7 cells. RESULTS AND CONCLUSION Eighteen 2-indolones were successfully synthesized and their structures were confirmed by 1H NMR and ESI-MS. Some compounds showed some c-Met kinase and MCF-7 cell proliferation inhibitory activity. The preliminary analysis of the structure-activity relationship of the target product has laid a foundation for further structural optimization of such compounds.