7673-83-8Relevant academic research and scientific papers
Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio‐Selectively Alkylated Benzimidazole 2‐Thione Derivatives
Amer, Mohamed R.,Eissa, Ibrahim H.,El Ashry, El Sayed H.,Elkaeed, Eslam B.,Elshobaky, Ahmed,Hafez, Elsayed E.,Khalid, Asaad,Metwaly, Ahmed M.,Mohammed, Salih Osman
, (2022/01/31)
The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio‐selectively alkylated benzimidazole‐2‐thione derivatives have been designed to carry the essential features of urease i
Mechanism of inhibition of H+, K+-ATPase by sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810)
Nochi, Shigeharu,Yokoyama, Yumi,Narukawa, Megumi,Ebine, Kumiko,Murahashi, Miho,Kawakami, Yoshiyuki,Asakawa, Naoki,Sato, Tadashi
, p. 552 - 558 (2007/10/03)
Sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810) and omeprazole inhibit gastric acid secretion through inhibition of the activity of H+, K+-ATPase present in parietal cell membrane vesicles, by chemical modification of SH groups in the enzyme molecule. In order to clarify the mechanism of the chemical modification, reaction products of E3810 and omeprazole with 2-mercaptoethanol under acidic conditions (pH 3, 4, 5, 6) were isolated by HPLC, and subjected to structural analysis by UV, 1H-NMR and mass spectrometry. E3810 and omeprazole appeared to undergo two kinds of reactions, affording disulfide-type products (type I reaction) and sulfide-type products (type II reaction). The rates of these reactions were determined by HPLC, and the stability of the products in the presence and absence of glutathione was investigated. In the case of E3810, type I reaction was found to proceed faster than type II reaction at every pH value studied. The type I reaction of E3810 was faster than that of omeprazole. The rate of type I reaction decreased at pH 5 and 6, especially for omeprazole, and the contribution of type II reaction increased as the pH of the reaction mixture was increased. The sulfide-type modification products were stable, whereas the formation of the disulfide-type modification products was reversed by the action of endogenous SH compounds such as glutathione. These results suggest that higher inhibitory activity of E3810 against gastric acid secretion and faster recovery of the enzyme activity after inhibition by E3810 can be expected, as compared with those of omeprazole.
Studies on antiulcer agents. III. Plausible mechanism of antisecretory action of ethyl 2-[(1h-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate, an H+/K+-ATPase inhibitor, based on its reaction with thiols
Terashima,Muraoka,Ono
, p. 1985 - 1991 (2007/10/03)
To explore the mechanism of the gastric antisecretion activity of ethyl 2- [(1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate (5), a potential H+/K+-ATPase inhibitor, in the acid compartment of parietal cells, its reaction with some alkylthiols in the presence of hydrochloric acid was investigated. Upon treatment with 2- mercaptoethanol under acidic conditions, 5 gave a characteristic 1:2 adduct, ethyl 4-[2-(2-hydroxyethyldithio)-1-(2- hydroxyethylthio)ethylidenamino]pyrimido[1,2-a]benzimidazole-3-carboxylate (6), instead of providing a disulfide of type 3, 2-(2- alkyldithiomethylpyridino)benzimidazolide, the product predicted to be formed according to the reaction mechanism of common H+/K+-ATPase inhibitors, such as omeprazole or lansoprazole, with mercaptans. With a large excess of 2- mercaptoethanol, 5 provided 2-(2-hydroxyethylthio)-1H-benzimidazole (8) and ethyl 4-dimethylamino-2-(2-hydroxyethyldithio)-5-pyrimidinecarboxylate (9) as well as 6. The transformation mechanisms and their implications are discussed.
