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.
Wang
Teng
T
Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People's Republic of China.
Dong
Ying
Y
Wang
Li-Chen
LC
Xiang
Bing-Ren
BR
Chen
Zhen
Z
Qu
Ling-Bo
LB
D000818:Animals; D002025:Bufonidae; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006835:Hydrazones / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000077464:Simendan; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D006835:Hydrazones; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan