Design,Synthesis And Anti-tumor Activity Study Of Small Molecule Compounds Containing A Thiophene Ring And Improved Synthesis Of Antithrombotics Betrixaban

This thesis contains two Parts:The design, synthesis and anti-tumor activity study of small molecule compounds containing a thiophene ring and the improved synthesis of antithrombotics betrixabanPart I: The design, synthesis and anti-tumor activity study of small molecule compounds containing a thiophene ring. Quinazoline nucleus, commonly used as antineoplastic, was replaced by a thiophene ring structure. P-nitrobenzyl bromide is main part of side chain, introduced morpholine and piperidine structure, and amide compound was produced by combining with basic skeleton. Thus 6 new molecules of compound with the above structure were obtained. The designed and synthesized compound had activity screening, selected two kinds of tumor cells of A549 and HepG2, and anti-tumor activity was tested by Alamar blue cell toxicity test method. The results showed that there were 4 compounds which had good inhibitory activity for two kinds of tumor.Part II: The improved synthesis of antithrombotics betrixaban. A new synthesis thinking was proposed based on analysis and research of known synthetic method of Betrixaban, i.e. set 5-methoxy-2-nitrobenzoic acid as raw material, 2-amino-5-methoxybenzoic acid was prepared by catalysis of palladium carbon and reduction of hydrogen at first, and N-（5-Chloro-2-pyridinyl）-2-[（4-cyanobenzoyl）amino]-5-methoxybenzamid e hydrochloride was obtained through two successive acylation processes; Betrixaban was produced through nucleophilic addition of the above product and dimethylamine, and total yield reached 61%. The synthesis way has few experimental procedures, high yield and suitable reaction condition, and it is easy to operate, which has a high value of industrial application.The structures of compounds were characterized by ¹H NMR and ¹³ C NMR.