2-[(2-Aminobenzyl)sulfinyl]-1-(2-pyridyl)-1,4,5,6-tetrahydrocyclopent[d]imidazoles as a novel class of gastric H+/K+-ATPase inhibitors
| Autor: | Tsunehiro Harada, Takeshi Yura, Koichiro Yamada, Masamichi Morimoto, Masaki Sugiura, Mine Kinoshita, Yasushi Honma, Masaki Yamada |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Stereochemistry Gastric Acid Rats Sprague-Dawley chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Moiety Imidazole Animals Enzyme Inhibitors Omeprazole chemistry.chemical_classification biology Bicyclic molecule Chemistry Imidazoles Proton Pump Inhibitors Rats Enzyme Mechanism of action Enzyme inhibitor Gastric Mucosa biology.protein Molecular Medicine Chemical stability medicine.symptom medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 39(2) |
| ISSN: | 0022-2623 |
| Popis: | Substituted 2-sulfinylimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The 4,5-unsubstituted imidazole series 6-11 and the 1,4,5,6-tetrahydrocyclopent[d]imidazole series 12 were found to be potent inhibitors of the acid secretory enzyme H+/K(+)-ATPase. Structure-activity relationships indicate that the substitution of 2-pyridyl groups at the 1-position of the imidazole moiety combined with (2-aminobenzyl)-sulfinyl groups at the 2-position leads to highly active compounds with a favorable chemical stability. Other substitution patterns in the imidazole moiety result in reducing biological activities. 2-[(2-Aminobenzyl) sulfinyl]-1-[2-(3-methylpyridyl)]-1,4,5,6-tetrahydrocyclopent++ ++ ++ [d]-imidazole (12h, T-776) was selected for further development as a potential clinical candidate. Extensive study on the acid degradation of 12h indicates a mechanism of action different from that of omeprazole, the first H+/K(+)-ATPase inhibitor introduced to the market. |
| Databáze: | OpenAIRE |
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