Design And Synthesis Of Novel Protein Tyrosine Kinase Inhibitor

Protein tyrosine kinase(PTK), as a class of kinase that catalyse the γ-phosphoric acid of ATP transferred to protein tyrosine, and it can catalyze various substrate protein tyrosine residues’ phosphorylation, so it plays an important role in cell growth, proliferation, and differentiation. Protein tyrosine kinases are the most common growth factor receptor of many tumor. Inhibiting the PTK’s activity can destruct the tumor cell’s signal transduction and inhibit tumor cell’s proliferation and new vascular formation, at the same time, it has less effect on the normal cells. Therefore, protein tyrosine kinase has become the hot target in tumor chemotherapy and its inhibitors are an important direction in antitumor research.The aim of this study was to design and synthesize some novel protein tyrosine kinase inhibitors and find some active compounds which have independent intellectual property rights through screening for further study. Achievement of this research is as follows:1A theoretical study of the2-indole ketone quantitative structure-activity relationship (QSAR) of protein tyrosine inhibitors what used the method of quantitative structure-activity relationship, designed a series of novel protein tyrosine kinase inhibitors with new structure and no reports guided by the QSAR studies of structure and combining with the existing in benzene and imidazoles QSAR research, formed into a virtual library of compounds.2The docking of novel novel protein tyrosine kinase inhibitors to human VEGFR-2was performed by DOCK6.0, as molecular docking software. The result of the docking was analyzed to select10high activity compounds. The situation of the inhibitor molecules and receptor binding sites was analyzed.3Substituted anilines as raw material, through a oxime, closed loop into isatin, hydrazine hydrate reduction reaction and other reactions synthesized a series of2-indole ketone derivatives, optimized the synthesis conditions, accumulated the experience of synthesizing protein tyrosine kinase inhibitor drugs4Substitute anilines as raw materials, via acyl amino protection, nitration, reduction and other reactions to syhthesize a series of Benzimidazol-2-carbaldehyde derivatives, explored the synthesis condition of Benzimidazole aldehyde and provided effectiv reference for the following synthesis work.