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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
1   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China
2   Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China
,
Ying Dong
1   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China
2   Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China
,
Li-Chen Wang
2   Department of Organic Chemistry, China Pharmaceutical University, Nanjing, The People’s Republic of China
,
Bing-Ren Xiang
1   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, The People’s Republic of China
,
Zhen Chen
3   Department of Pharmacology, China Pharmaceutical University, Nanjing, The People’s Republic of China
,
Ling-Bo Qu
4   Department of Chemistry, Zhengzhou University, Zhengzhou, The People’s Republic of China
› Author Affiliations
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Publication History

Publication Date:
19 December 2011 (online)

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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
 

  • References

  • 1 Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldmanmd AM, Francis GS et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation. 2001; 104: 2996-3007
    CrossrefPubMedGoogle Scholar
  • 2 Balakumar P, Singh AP, Singh M. Rodent models of heart failure. J Pharmacol Toxicol. 2007; 56: 1-10
    CrossrefPubMedGoogle Scholar
  • 3 Mendez GF, Cowie MR. The epidemiological features of heart failure in developing countries: a review of the literature. Int J Cardiol. 2001; 80: 213-219
    CrossrefPubMedGoogle Scholar
  • 4 Jessup M, Brozena S. Heart Failure. N Engl J Med. 2003; 348: 2007-2018
    CrossrefPubMedGoogle Scholar
  • 5 Vogels RLC, Scheltens P, Schroeder-Tanka JM, Weinstein HC. Cognitive impairment in heart failure: A systematic review of the literature. Eur J Heart Fail. 2007; 9: 440-449
    CrossrefPubMedGoogle Scholar
  • 6 Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T et al. Heart Disease and Stroke Statistics-2006 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006; 113: e85-e151
    CrossrefPubMedGoogle Scholar
  • 7 Nadler G, Delimoge I, Lahouratate P, Leger I, Morvan M, Zimmermann RG et al. Stereospecificity of myofibrillar calcium sensitivity and PDE inhibition in cardiotonic thia-diazinones. Eur J Med Chem. 1996; 31: 805-812
    CrossrefPubMedGoogle Scholar
  • 8 Wang T, Dong Y, Wang LC, Chen Z. Synthesis and Bioactivity of 6-Phenyl-4,5-dihydro-3(2H)-pyridazinone Derivatives. Arzneimittel-Forschung (Drug Research). 2007; 57: 641-646
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Pawlak Z. Rough Set Theory and its Applications to Data Analysis. Cybernet Syst. 1998; 29: 661-668
    CrossrefPubMedGoogle Scholar
  • 10 Witlox F, Tindemans H. The application of rough sets analysis in activity-based modelling. Opportunities and constraints. Expert Syst Appl. 2004; 27: 585-592
    CrossrefPubMedGoogle Scholar
  • 11 Pawlak Z. Rough sets and intelligent data analysis. Inform Sri. 2002; 147: 1-12
    PubMedGoogle Scholar
  • 12 Wilk SZ, Slowinski R, Michalowski W, Greco S. Supporting triage of children with abdominal pain in the emergency room. Eur J Oper Res. 2005; 160: 696-709
    CrossrefPubMedGoogle Scholar
  • 13 Tay FEH, Shen LX. Fault diagnosis based on Rough Set Theory. Eng Appl Artif Intel. 2003; 16: 39-43
    CrossrefPubMedGoogle Scholar
  • 14 Walczak B, Massart DL. Rough sets theory. Chemometr Intell Lab. 1999; 47: 1-16
    CrossrefPubMedGoogle Scholar
  • 15 Liu H, Xiang BR, Qu LB. The application of rough sets in SAR analysis of N1-site substituted fluoroquinolones. Chemometr Intell Lab. 2007; 87: 155-160
    CrossrefPubMedGoogle Scholar
  • 16 Hai-Jun Zhou, Shi-xian Deng. Pharmaceutical experiments on isolated heart preparations. In: Shu-Yun Xu, Ru-Lian Bian, Xiu Chen. eds The methodology of pharmaceutical experiment. Beijing: People’s Medical Publishing House; 1991. p. 863-864
    Google Scholar
  • 17 Predki B, Slowinski R, Stefanowski J, Susmaga R, Wilk Sz. ROSE–Software Implementation of the Rough Set Theory. In: Polkowski L, Skowron A. eds. The Rough Sets and Current Trends in Computing, Lecture Notes in Artificial Intelligence. Vol. 1424 Berlin: Springer-Verlag; 1998. p. 605-608
    CrossrefGoogle Scholar
  • 18 Predki B, Wilk Sz. Rough Set Based Data Exploration Using ROSE System. In: Ras ZW, Skowron A. eds. In: The Foundations of Intelligent Systems, Lecture Notes in Artificial Intelligence. Vol. 1609 Berlin: Springer-Verlag; 1999. p. 172-180
    Google Scholar
  • 19 Younkin JM, Smith LJ, Compton RN. Semi-Empirical Calculations of re-Electron Affinities for Some Conjugated Organic Molecules. Theoret Chim Acta. 1976; 41: 157-176
    CrossrefPubMedGoogle Scholar