Nonsteroidal cardiotonics. 1. 2-Pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones, a novel class of cardiotonic agents

A series of substituted 2-pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones 1-24 were synthesized and evaluated for positive inotropic activity. In rats, cats, and dogs most of these tricyclic heterocycles produced a dose-related increase in myocardial contractility with little effect on h...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1987-08, Vol.30 (8), p.1279-1287
Main Authors: Mertens, A, Mueller-Beckmann, B, Kampe, W, Hoelck, J. P, Von der Saal, W
Format: Article
Language:English
Subjects:
Animals
Benzimidazoles - chemical synthesis
Benzimidazoles - pharmacology
Blood Pressure - drug effects
Cardiotonic Agents
Cats
Chemical Phenomena
Chemistry
Dogs
Dose-Response Relationship, Drug
Female
Heart Rate - drug effects
Male
Myocardial Contraction - drug effects
Pyridines - chemical synthesis
Pyridines - pharmacology
Pyrroles - chemical synthesis
Pyrroles - pharmacology
Rats
Stimulation, Chemical
Structure-Activity Relationship
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Summary:A series of substituted 2-pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones 1-24 were synthesized and evaluated for positive inotropic activity. In rats, cats, and dogs most of these tricyclic heterocycles produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. The increase in contractility was not mediated via stimulation of beta-adrenergic receptors. Compound 1 (BM 14.478) was more potent than milrinone (25) and enoximone when administered intravenously to rats, cats, and dogs. After oral administration of 1 mg/kg, compound 1, milrinone, and pimobendan were equipotent. However, only 1 and pimobendan were still active after 6 h. The structural requirements necessary for optimal cardiotonic activity within this novel class of heterocycles were investigated.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00391a004