VEGFR-2酪氨酸激酶抑制剂3-取代吲哚-2-酮的合成及抑制活性

Synthesis and inhibition activity of 3-substituted indolin-2-ones as inhibitors of VEGFR-2 tyrosine kinase

目的:合成一系列结构新颖的3-取代吲哚-2-酮类化合物,并测试其对血管内皮生长因子受体-2(VEGFR-2)的抑制活性。方法:以2-(羟甲基)-5-氰基-1H-吲哚为起始原料,经水解、氧化、缩合和胺化反应得到目标产物(6-14);以舒尼替尼为阳性对照,用MTT法测试目标产物对VEGFR-2高表达的人乳腺上皮细胞(HMEC)的抑制活性。结果:合成9个未见报道的目标产物,其结构均经1H NMS,ESI-MS确证;样品浓度为10μmol/L时,化合物14对VEGFR-2的抑制率为68.56%,舒尼替尼为62.53%。结论:化合物14对VEGFR-2的抑制活性优于阳性对照舒尼替尼。

Objective： To synthesize a series of novel 3 substituted indolin-2-ones and to determine their inhibitory activity against vascular endothelial growth factor receptor 2 （VEGFR 2）. Methods： 2-（ hydroxymethyl）-5- carbonitrile-1 H-indole were used as the starting material, target compounds were synthesized via hydrolyzation, oxidation, condensation and amination reaction. The activities of the target compounds were evaluated with HMEC （on kind of cell lines high expressing VEGFR-2 tyro.sine kinase） in vitro through measuring cell viability by MTT method and sunitinib was a positive control. Results： There are no reports for the synthesis of target compounds and their structures were identified by ^1 H NMS, MS. At the concentration of 10 mol/L, compound 14 showed 68.56% inhibitory activity against VEGFR 2, while the inhibition ratio of sunitinib was 62.53%. Conclusion： Compound 14 shows higher inhibition ratio against VEGFR 2 than that of sunitinib.