Synthesis And Antitumor Activity Of Benzimidazole Tyrosine Kinase Inhibitors, Inclusion Behavior Of Cyclodextrin And Oxaliplatin And Small Trial Process Of Key Intermediates Of Parecoxib Sodium

This thesis includes three parts. The first chapter is research on the synthesis and antitumor activity of benzimidazole VEGFR-2 tyrosine kinase protein inhibitors. The second chapter is study on the synthesis and antitumor activity of oxaliplatin/CDs.And the third chapter is about research on the synthesis of parecoxib sodium’s key intermediates.Chapter one introduces the synthesis and antitumor activity of benzimidazole VEGFR-2 tyrosine kinase protein inhibitors.This chapter is divided into three sections. The first section mainly introduces the source, mechanism and applications of different VEGFR-2 tyrosine kinase protein inhibitors. The second section is mainly about the synthesis methods of VEGFR-2 tyrosine kinase protein inhibitors. We filtered and optimized the solvents, temperature, time, reagents ratio and so on, confirming a simple and efficient synthesis route at last.And we synthesized a series of benzimidazole amide compounds and benzimidazole urea linkage compounds which possess different substituent groups. Meanwhile, we tested the chicken embryo blood vessel growth, and the cytotoxicity of these compounds against HCT116 and A549 cells which were individually evaluated using the MTT assay. Experiment procedure, physical and spectral data for all compounds are recorded in section three.Chapter two is mainly about research on oxaliplatin/CDs complexs.This chaptert includes two sections. Section one summarizes the recent advances and applications of cyclodextrins and oxaliplatin. Oxaliplatin/CDs complexs can improve the stability and bioavailability of drug molecules, so the research on oxaliplatin/CDs complexs is of important significance and practical application value. The other section is experimental part.Three water-soluble oxaliplatin/CD complexes were prepared by inclusion complexation of oxaliplatin and CDs. The structures of oxaliplatin/CDs were confirmed by NMR, FTIR, TGA, XRD as well as SEM analysis. Meanwhile, the cytotoxic activities of oxaliplatin/CD complexes against HCT116 and MCF-7 cells have been stueied.Chapter three is mainly about research on the synthesis of parecoxib sodium’s key intermediate.This chapter can be divided into two sections. Section one summarizes the development and application of parecoxib sodium. Parecoxib sodium is efficient anti-inflammatory and antipyretic drugs. So far, the development of parecoxib sodium is limited and most of the drugs need to be import. Therefore, KPC aims to develop a new synthesis method of parecoxib sodium. Our purpose is to develop green environmental, efficient and easy industrial synthesis methods of key intermediate.The research on the synthesis parecoxib sodium’s key intermediate 5-methyl-3,4- diphenylisoxazole is so necessary. Section two is about experiment. It includs the exploration and optimize of synthesis methods and experiment procedure, physical and spectral data.