Structure-activity relationships of arylimidazopyridine cardiotonics: discovery and inotropic activity of 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine
| Autor: | David W. Robertson, H. Wilson, E. E. Beedle, Hayes Js, G. D. Pollock, J. H. Krushinski, V. L. Wyss |
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| Rok vydání: | 1985 |
| Předmět: |
Inotrope
Purine Male Cardiotonic Agents Bicyclic molecule Stereochemistry Cardiotonic drugs Imidazoles In Vitro Techniques Myocardial Contraction Amrinone chemistry.chemical_compound Structure-Activity Relationship Orally active Dogs chemistry Drug Discovery Pyridine medicine Cats Molecular Medicine Structure–activity relationship Animals Female medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 28(6) |
| ISSN: | 0022-2623 |
| Popis: | Recently several noncatecholamine, nonglycoside cardiotonic drugs have been discovered that possess both inotropic and vasodilator activities in experimental animals and man. Prototypical compounds include amrinone, sulmazole, and fenoximone. We investigated the structural requirements necessary for optimal inotropic activity in a series of molecules containing a heterocyclic ring fused to 2-phenylimidazole and discovered that 2-phenylimidazo[4,5-c]pyridines were generally 5-10-fold more potent than analogous 2-phenylimidazo[4,5-b]pyridines (e.g., sulmazole) or 8-phenylpurines. Furthermore, all imidazo[4,5-c]pyridine analogues we tested were orally active; in contrast, only one of the imidazo[4,5-b]pyridine derivatives, sulmazole, was significantly active. One of several highly active compounds in the [4,5-c] series was 50 (LY175326, 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine hydrochloride). The structure-activity relationship of this series is presented and compared to that of the imidazo[4,5-b]pyridine and purine series. |
| Databáze: | OpenAIRE |
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