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 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.
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D002316:Cardiotonic Agents; D011725:Pyridines; D011758:Pyrroles