N-aryl-substituted Isothiourea Class H ~ + / K ~ +-atpase Inhibitor Of The Synthesis And Activity Of Research

H+/K+-ATPase inhibitor has become novel type of antiulcer drug with inhibition of gastric acid secretion after the appearance of histamine H2-receptor antagonist. In this thesis we briefly summarized the mechanism and the progress of the H+/K+-ATPase inhibitors. On the base of our former research work, we designed and synthesized pyridine and quinoline derivatives as new types isothioureas to study the QSAR of the H+/K+-ATPase inhibitor. We totally synthesized 20 new N-arylisothiourea derivatives and indentified their structures by 1H-NMR, 13C-NMR and MS.The method of affusing the dissociated stomach of the big rat was used to study the changing of the gastric acid secretion effected by the target compounds. The result shows that 12 of the target compounds have comparable or strong gastric acid inhibitory activities with the positive control sodium pantoprazolc. Especially, compound BTU-08 gave the most powerful activity which was nearly two times higher than the control. And the bioactivity of the quinoline derivatives is better than the pyridine derivatives.Using the compound bioactivities we studied the QSAR of the N-arylisothioureas by CoMFA computation. And we got the regular how the steric factor and electrostatic factor effect on the bioactivity. And we also predicted the model structure which will have more powerful bioactivity based on the regular. This regular will benefit the work of modifying the molecular to find the better H+/K+-ATPase inhibitor in the future.