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

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-1H-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 tyrosine 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 1H 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.