Molecular structure of the dihydropyridazinone cardiotonic 1, 3-dihydro-3, 3-dimethyl-5-(1, 4, 5, 6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one, a potent inhibitor of …

DW Robertson, ND Jones, JH Krushinski…

Index: Robertson, David W.; Jones, Noel D.; Krushinski, Joseph H.; Pollock, G. Don; Swartzendruber, John K.; Hayes, J. Scott Journal of Medicinal Chemistry, 1987 , vol. 30, # 4 p. 623 - 627

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Citation Number: 32

Abstract

The cardiotonic 1, 3-dihydro-3, 3-dimethyl-5-(1, 4, 5, 6-tetrahydro-6-oxo-3-pyridazinyl)-2H- indol-2-one (1, LY 195115) is a potent, competitive inhibitor (Ki= 80 nM) of sarcoplasmic reticulum derived phosphodiesterase (SR-PDE). Moreover, the compound is a potent positive inotrope both in vitro and in vivo. To assist further cardiotonic drug-design studies, we have mapped the three-dimensional structure of 1 using X-ray crystallography. From a ...