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

Article abstract of DOI:10.1021/jm00391a004

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 β-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.