| Peptic ulcer is a common and frequently encountered disease with a morbidity rate of 15% in the whole population. This kind of disease is mainly caused by the over-secretion of gastric acid. Therefore, drugs with inhibitory activities of gastric acid secretion are still one of hotspot in the field of drug research and development. In this thesis, we briefly summarized the pharmacological mechanism of the peptic ulcer and the progress of the anti-peptic ulcer drugs.IY-81149(Ilaprazole) is novel proton pump inhibitor which had been newly developed by Ilyang Medicines and Chemical Reagents Limited-Liability Company in 1995,which structure has the unit of the 5-(1H-pyrrol-1-y1)-1H-benzo[d]imidazole-2-thiol. Based on "me too" strategy, 18 new indolylbenzoimidazole derivatives were designed and synthesized, and their structures were confirmed by 1H-NMR and LC-MS.By trial and error, the target compounds were obtained through one of designed route as following: N-(4-iodo-2-nitrophenyl)acetamide was got from starting material 2-nitrobenzenamine,and then the key intermediate N-(4-(1H-indol-1-yl)-2-nitrophenyl)acetamide was given by Ullmann reaction under using CuI as catalyst and L-proline as lagand. After de-protection, reduction and cyclization, 5-(1H-indol-1-yl)-1H-benzo[d]imidazole-2-thiol was synthesized successfully. The compound thioethers were obtained via condensation of 5-(1H-indol-1-yl)-1H-benzo[d]imidazole-2-thiol and chloromethyl pyridine derivates. The compounds sulphoxides and sulfones were obtained via oxidization of corresponding thioethers by using M-CPBA and sodium tungstate/hydrogen peroxide respectively.As a result of the in vivo screening of the model of pylorecs ligated in rat, 14 of the target compounds were found having strong gastric acid inhibitory activities. Especially, compound BO-02 showed the most powerful activity and without statistics difference compare to the positive contrast sodium pantoprazole, future study will be needed. |
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