2-[(2-Pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K+-ATPase inhibitors
| Autor: | Robert Rippel, Lang Hans Jochen, Klaus Dr Weidmann, Hildegard Nimmesgern, Andreas W. Herling, Scheunemann Karl-Heinz, H. Metzger, Thomas Scholl, Martin Bickel |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Bicyclic molecule Stereochemistry Stomach Imidazoles Rats Inbred Strains Sulfoxide Biological activity Rats Structure-Activity Relationship chemistry.chemical_compound Dogs chemistry Drug Discovery Alkoxy group Animals Molecular Medicine Moiety Imidazole Structure–activity relationship Gastric acid Female Enzyme Inhibitors Sodium-Potassium-Exchanging ATPase Omeprazole |
| Zdroj: | Journal of Medicinal Chemistry. 35:438-450 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00081a004 |
| Popis: | 2-[(2-Pyridylmethyl)sulfinyl]thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The [3,4-d] isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo. Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thieno[3,4-d]imidazole lead to highly active compounds with a favorable chemical stability. Various substitution patterns in the thieno[3,4-d]imidazole moiety result in lower biological activity. The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation. Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K(+)-ATPase blocker introduced on the market. |
| Databáze: | OpenAIRE |
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