Dihydropyridazinone cardiotonics. The discovery and inotropic activity of 1, 3-dihydro-3, 3-dimethyl-5-(1, 4, 5, 6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one

DW Robertson, JH Krushinski, EE Beedle…

Index: Robertson; Krushinski; Beedle; Wyss; Pollock; Wilson; Kauffman; Hayes Journal of Medicinal Chemistry, 1986 , vol. 29, # 10 p. 1832 - 1840

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Citation Number: 71

Abstract

We discovered that 6 (N-[4-(1, 4, 5, 6-tetrahydr0-6-0~ 0-3-pyridazinyl) phenyl] acetamide) is a potent positive inotrope in dogs, and we have prepared several lactam analogues of this agent. These included 16 (1, 3-dihydro-5-(1, 4, 5, 6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol- 2-one), 32 (the analogous quinolin-2-one), and 37 (the analogous benzazepin-2-one). The inotropic ED,'s of these compounds were 24, 3.3, and 5.2 gglkg, respectively, after iv ...