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Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives


A series of pyridazinone-containing compounds were designed and synthesized as congeners for diclofenac, the most potent and widely used NSAID. The target compounds were evaluated for their anti-inflammatory activity on rat paw edema inflammation model against diclofenac as a reference compound. Seven of the tested compounds demonstrated more than 50% inhibition of carrageenan-induced rat paw edema at a dose 10 mg/kg. The compounds, 6-(2-bromophenylamino)pyridazin-3(2H)-one 2a and 6-(2,6-dimethylphenylamino)pyridazin-3(2H)-one 2e, displayed 74 and 73.5% inflammation-inhibitory activity, respectively, which is comparable to diclofenac (78.3%) at the same dose level after 4 h. The most active compounds as anti-inflammatory agents, 2a, 2e, and 6a, displayed fewer number of ulcers and milder ulcer score than indomethacin in ulcerogenicity screening.

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  • Abouzid K, Bekhit SA (2008) Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity. Bioorg Med Chem 16:5547–5556

    Article  PubMed  CAS  Google Scholar 

  • Allison MC, Howatson AG, Torranc CJ, Lee FD, Russell RIG (1992) Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 327:749–754

    Article  PubMed  CAS  Google Scholar 

  • Boissier JR, Ratouis R, Dumont C (1963) Synthesis and pharmacological study of new piperazine derivatives I benzylpiperazines. J Med Chem 6:541–544

    Article  PubMed  CAS  Google Scholar 

  • Chintakunta VK, Akella V, Vedula MS, Mamnoor PK, Mishra P, Casturi SR, Vangoori A, Rajagopalan R (2002) 3-O-Substituted benzyl pyridazinone derivatives as COX inhibitors. Eur J Med Chem 37:339–347

    Article  PubMed  CAS  Google Scholar 

  • Clementi G, Caruso A, Cutuli VMC, deBernardis E, Prato A, Mangano NG, Amico-Roxas M (1998) Effects of centrally or peripherally injected adrenomedullin on reserpine-induced gastric lesions. Eur J Pharmacol 360:51–54

    Article  PubMed  CAS  Google Scholar 

  • Dogne JM, Supuran CT, Pratico D (2000) Adverse cardiovascular effects of the coxibs. J Med Chem 48:2251–2257

    Article  Google Scholar 

  • Gleave RJ, Beswick PJ, Brown AJ, Giblin GMP, Goldsmith P, Haslam CP et al (2010) Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain. Bioorg Med Chem 20:465–468

    Article  CAS  Google Scholar 

  • Gökce M, Utku S, Küpeli E (2009) Synthesis and analgesic and anti-inflammatory activities 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted/non substituted benzal)hydrazone derivatives. Eur J Med Chem 44:3760–3764

    Article  PubMed  Google Scholar 

  • Graham DJ, Campen D, Hui R, Spence M (2005) Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. The Lancet 365(9458):475–481

    CAS  Google Scholar 

  • Hsiao F-Y, Tsai Y-W, Huang W-F (2009) Changes in physicians’ practice of prescribing cyclooxygenase-2 inhibitor after market withdrawal of rofecoxib: a retrospective study of physician-patient pairs in Taiwan. Clin Ther 31(11):2618–2627

    Article  PubMed  Google Scholar 

  • Lanas A, Rodriguez LAG, Arroyo MT, Gomollon F, Feu F, Gonzalez-Pérez A et al (2006) Risk of upper gastrointestinal ulcer bleeding associated with selective cyclooxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 55(12):1731–1738

    Article  PubMed  CAS  Google Scholar 

  • Oyagi A, Ogawa K, Kakino M, Hara H (2010) Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice. BMC Complement Altern Med 10:45–53

    Article  PubMed  Google Scholar 

  • Süküroglu M, Çaliskanergun B, Ünlü S, Sahin MF, Küpelli E, Yesilada E, Banoglu E (2005) Synthesis, analgesic, and anti-inflammatory activities of [6-(3, 5-dimethyl-4-chloropyrazole-1-yl)-3(2H)-pyridazinon-2-yl] acetamides. Arch Pharm Res 28:509–517

    Article  PubMed  Google Scholar 

  • Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 111:544–547

    PubMed  CAS  Google Scholar 

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Correspondence to K. A. M. Abouzid.

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Abouzid, K.A.M., Khalil, N.A., Ahmed, E.M. et al. Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives. Med Chem Res 21, 3581–3590 (2012).

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