Synthesis Of Tetramethylpyrazine Derivatives And Their Anti - Ulcer Activity

H⁺/K⁺-ATPase inhibitor is a novel antiulcer drug which inhibits the secretion of gastric acid after the appearance of histamine H₂-receptor antagonist.In this thesis the mechanism and development of the H⁺/K⁺-ATPase inhibitors are summarized.The H⁺/K⁺-ATPase inhibitor has much better clinical effect than the histamine H₂-receptor antagonist,however,some disadvantages appear as it is commonly used,for example,the inhibition of the enzyme is too strong and too long,resulting in achlorhydria, followed by dyspepsia and hypergastrinemia.The purpose of this thesis is to provide some compounds which have the activity of anti-gastric ulcer and can protect the gastric mucosa.Ligustrazine promotes the release of the nitric oxide,obviously eliminates the oxygen free radical and plays an important role in the protection of the gastric mucosa.We introduced the ring of pyrazine instead of the ring of pyridine to change the structure of the traditional H⁺/K⁺-ATPase inhibitor.12 new tetramethylpyrazine derivatives were synthesized and their structures were certified by using 1H-NMR and MS spectroscopy.HL-06、HL-08、HL- 12、HL- 13、HL- 14、HL- 15及HL- 16 were assayed for the anti-gastric ulcer activity by using water immersion-restraint stress（WRS）model in mice and alcohol induced gastric damage model（HL-07、HL-09、HL-10、HL-11、HL-17 were under test）.The data show that the target compounds have good protection of the gastric mucosa,which is in accordance with the design idea.The synthesis of the ligustrazine derivatives and the research on their anti-gastric ulcer activity in this thesis provide information for further research.