Design, Synthesis and Structure-Activity Relationship Studies of 6-Phenyl-4,5-dihydro-3(2H)-pyridazinone Derivatives as Cardiotonic Agents

Teng Wang; Ying Dong; Li-Chen Wang; Bing-Ren Xiang; Zhen Chen; Ling-Bo Qu

doi:10.1055/s-0031-1296558

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2008; 58(11): 569-573
DOI: 10.1055/s-0031-1296558

Cardiac Drugs · Cardiac Stimulants · Coronary Drugs

Editio Cantor Verlag Aulendorf (Germany)

Design, Synthesis and Structure-Activity Relationship Studies of 6-Phenyl-4,5-dihydro-3(2H)-pyridazinone Derivatives as Cardiotonic Agents

Teng Wang

¹Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China

²Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China

,

Ying Dong

¹Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China

²Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China

,

Li-Chen Wang

²Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China

,

Bing-Ren Xiang

¹Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China

,

Zhen Chen

³Department of Pharmacology, China Pharmaceutical University, Nanjing, The People’s Republic of China

,

Ling-Bo Qu

⁴Department of Chemistry, Zhengzhou University, Zhengzhou, The People’s Republic of China

› Author Affiliations

Abstract

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-l,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-l,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, levosim-endan (CAS 141505-33-1). The structure activity relationships of the compounds were studied using the rough sets theory.

Key words

Cardiotonic agents - CAS 141505-33-1 - Levosimendan - 3(2H)-Pyridazinones, cardiotonic activity, structure-activity relationship, synthesis

Full Text

References

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