Study On The Design, Synthesis And Antitumor Activity Of 4 - Substituted Aniline - 6 - Methoxy - 7 - Alkoxybenzotriazine Compounds

Tyrosine Kinases (RTKs) and their receptors play a crucial role in the interrelated generative process of tumor growth, infiltration and metastasis. Tyrosine Kinase Inhibitors of multitargeted receptors can inhibit the self-phosphorylation of RTKs receptors, through competing with ATP to combine with binding site of ATP in the intramembrane of receptors, and then suppress tyrosine phosphorylation on substrate. Vascular endothelial cell growth can be suppressed. Tumor growth and metastasis can be inhibited finally.4-sustituted anilino-1,2,3-benzotriazine was taken as the leading compound, and synthesises with alkyl and heterocycles at C-7 position. Thirty compounds of 4-substitutedanilino-6-methoxy-7-substitutedalkoxyl-1,2,3-benzotriazines were designed and synthesized, all the target compounds are new compounds which have been characterized by 1H-NMR, IR and MS.Taking Vatalanib(PTK787) as comparison, the growth inhibition of target compounds were determined in MDA-MB-468 cells by Western Blot method. Compounds MAX01, MAX02, MAX07, MAX10, MAX15, MAX21, MAX22, MAX28, MAX30 had competitive activities with Vatalanib in 10μg/ml. They are worth of deeply investigation. Compounds MAX08, MAX16-18, MAX23, MAX 24, MAX26, MAX29 had partly inhibitory effect. The inhibitiory effect of VEGFR is in Progress.