4-Aroyl-1,3-dihydro-2H-imidazol-2-ones, a new class of cardiotonic agents

A series of 4-aroyl-1,3-dihydro-2H-imidazol-2-ones was synthesized and evaluated for pharmacological activity in the anesthetized dog. Most members of this series produced dose-related increases in cardiac contractile force as well as relatively minor increases in heart rate and decreases in systemi...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1982-12, Vol.25 (12), p.1477-1481
Main Authors: Schnettler, Richard A, Dage, Richard C, Grisar, J. Martin
Format: Article
Language:English
Subjects:
Animals
Blood Pressure - drug effects
Cardiac Output - drug effects
Cardiotonic Agents - chemical synthesis
Chemical Phenomena
Chemistry
Dogs
Female
Heart Rate - drug effects
Hemodynamics - drug effects
Imidazoles - chemical synthesis
Imidazoles - pharmacology
Male
Myocardial Contraction - drug effects
Pentobarbital - antagonists & inhibitors
Propranolol - pharmacology
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Summary:A series of 4-aroyl-1,3-dihydro-2H-imidazol-2-ones was synthesized and evaluated for pharmacological activity in the anesthetized dog. Most members of this series produced dose-related increases in cardiac contractile force as well as relatively minor increases in heart rate and decreases in systemic arterial blood pressure that were not blocked by propranolol. In general, 4-methoxy or 4-methylthiobenzoyl substitution afforded compounds of greatest inotropic potency. 1,3-Dihydro-4-(4-methoxybenzoyl)-5-methyl-2H-imidazol-one (6) was shown to produce a dose-related positive inotropic effect and reverse the depressant effect of pentobarbital on cardiac pump function in the dog heart-lung preparation. The cardiotonic activity of this series may have important utility in the treatment of congestive heart failure. 1,3-Dihydro-4-[4-(methylthio)benzoyl]-5-methyl-2H-imidazol-2-one (17) was chosen for human studies and is currently undergoing clinical trials.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00354a017