Design, synthesis and structure-activity relationship studies of 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives as cardiotonic agents.

Based on our previous study, a variety of 12 novel 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives were synthesized. The structures attributed to the compounds were elucidated using IR, 1H-NMR and mass spectra. The cardiotonic activities of these compounds were assessed by Straub's perfusion method and a clear cardiotonic effect was shown for compounds 1c (2,3-dichloro-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)phenyl) benzamide), 1d (4-amino-3-methyl-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl) phenyl)benzamide), 2a (3-methyl-4-nitro-N-(4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)phenyl)benzamide) and 2d (4-amino-3-methyl -N-(4-(6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl) benzamide) when compared to another 3(2H)-pyridazinone derivative, levosimendan (CAS 141505-33-1). The structure-activity relationships of the compounds were studied using the rough sets theory.