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 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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010424:Pentobarbital / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000494:pharmacology
D002316:Cardiotonic Agents; D007093:Imidazoles; D011433:Propranolol; D010424:Pentobarbital