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Synthesis, Analgesic, and Anti-Inflammatory Activities of [6-(3,5-Dimethyl-4-Chloropyrazole-1-yl)-3(2H)-Pyridazinon-2-yl]Acetamides

Sukuroglu, Murat    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University   ); Caliskanergun, Burcu    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University   ); Unlu, Serdar    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University   ); Sahin, M.Fethi    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University   ); Kupeli, Esra    (Department of Pharmacognosy, Faculty of Pharmacy, Gazi University   ); Yesilada, Erdem    (Department of Pharmacognosy, Faculty of Pharmacy, Gazi University   ); Banoglu, Erden    (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University  );
  • 초록

    A series of structurally diverse amide derivatives of [6-(3,5-dimethyl-4- chloro-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone-induced writhing test and carrageenan induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds, 7c, 7d and 7k were found to be equipotent to aspirin (as an analygesic) and indometacin (as an anti-inflammatory drug), respectively. The other amide derivatives generally resulted in lower activity on comparision with reference compounds.


  • 주제어

    Pyridazinone .   Pyrazole .   Analgesic .   Anti-Inflammatory .   Writhing .   Carrageenan.  

  • 참고문헌 (28)

    1. Coudert, P., Rubat, C., Rohet, F., Leal, F., Fialip, J., and Couquelet, J., Synthesis of new pyridazinones substituted by 4-arylpiperazine-1-yl-carbonyl alkyl moieties and their analgesic properties in mice. Pharm. Pharmacol. Commun., 6, 387-396 (2000) 
    2. Druey, J., Meier, Kd., and Eichenberger, K., Heilmittelchemiseke Studies in der heterocyclischen Reihe I. Helv. Chim. Acta, 37, 121-131 (1954) 
    3. Kalgutkar, A. S., Rowlinson, S. W., Crews, B. C., and Marnett, L. J., Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett., 12, 521-524 (2002) 
    4. Takaya, M., Sato, M., Terashima, K., and Tanizawa, H., A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)- pyridazinone and related compounds. J. Med. Chem., 22, 53-58 (1979) 
    5. Brooks, P., Emery, P., Evans, J. F., Fener, H., Hawkey, C. J., Patrono, C., Smolen, J., Breedveld, F., Day, R., Dougados, M., Ehrich, E. W., Gijon-Banos, J., Kvien, T. K., Van Rijswijk, M. H., Warner, T., and Zeidler, H., Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. Rheumatology, 38, 779-788 (1999) 
    6. Gokce, M., Sahin, M. F., Kupeli, E., and Yesilada, E., Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives. Arzneim. Forsch./ Drug Res., 54, 396-401 (2004) 
    7. Vinegar, R., Truax, J. F., Selph, J. L., Johnston, P. R., Venable, A. L., and McKenzie, K. K., Pathway to carrageenan-induced inflammation in the hind limb of the rat. Fed. Proc., 46, 118- 126 (1987) 
    8. Kalgutkar, A. S., Marnett, A. B., Crews, B. C., Remel, R. P., and Marnett, L. J., Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indometacin, as selective cyclooxygenase- 2 inhibitors. J. Med. Chem., 43, 2860-2870 (2000) 
    9. Banoglu, E., Akoglu, C., Unlu, S., Kupeli, E., Yesilada, E., and Sahin, M. F., Amide derivatives of [6-(5-Methyl-3-phenyl-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acids as potential analgesic and anti-inflammatory compounds. Arch. Pharm., 337, 7-14 (2004). 
    10. Clinch, D., Banerjee, A. K., Ostick, G., and Levy, D. W., Nonsteroidal anti-inflammatory drugs and gastrointestinal adverse effects. J. R. Coll. Physicians Lond., 17, 228-230 (1983) 
    11. Dogruer, D. S., Sahin, M. F., Unlu, S., and Shigeru, I., Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity. Arch. Pharm., 333, 79-86 (2000) 
    12. Rubat, C., Coudert, P., Albuisson, E., Bastide, J., Couquelet, J., and Tronche, P., Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents. J. Pharm. Sci., 81, 1084- 1087 (1992) 
    13. Kasahara, Y., Hikino, H., Tsurufuji, S., Watanabe, M., and Ohuchi, K., Antiinflammations Actions of Ephedrines in Acute Inflammations. Planta Med., 51, 325-331 (1985) 
    14. Rubat, C., Coudert, P., Tronche, P., Bastide, J., Bastide, P., and Privat, A. M., Synthesis and Pharmacological Evaluation of N-Substituted 4,6-Diaryl-3-pyridazinones as Analgesic, Antiinflammatory and Antipyretic Agents. Chem. Pharm. Bull., 37, 2832-2835 (1989) 
    15. Dal Piaz, V., Giovannoni, M. P., Ciciani, G., Barlocco, D., Giardina, G., Petrone, G., and Clarke, G. D., 4,5-Functionalized 6- Phenyl-3(2H)-pyridazinones: Synthesis and Evaluation of Antinociceptive Activity. Eur. J. Med. Chem., 31, 65-70 (1996) 
    16. Gokce, M., Dogruer, D., and Pahin, M. F., Synthesis and antinociceptive activity of 6-substituted-3-pyridazinone derivatives. Farmaco, 56, 233-237 (2001) 
    17. Pieretti, S., Dal Piaz, V., Matucci, R., Giovannoni, M. P., and Galli, A., Antinociceptive activity of a 3(2H)-pyridazinone derivative in mice. Life Sci., 65, 1381-1394 (1999) 
    18. Rubat, C., Coudert, P., Couquelet, J., Bastide, P., and Bastide, J., Synthesis and analgesic effect of N-substituted 5- arylidene-6-methyl-3(4H)-pyridazinones. Chem. Pharm. Bull., 36,1558-1561 (1988) 
    19. Szilagyi, G., Kasztreiner, E., Tardos, L., Jaszlits, L., Kosa, E., Cseh, G., Tolnay, P., and Kovacs-Szabo, I., Studies in the field of pyridazine compounds, III (1). Hypotensive 3-(1- Pyrazolyl)-pyridazine derivatives. Eur. J. Med. Chem., 14, 439-445 (1979) 
    20. Vinegar, R., Schreiber, W., and Hugo, R., Biphasic development of carrageenin edema in rats. J. Pharmacol. Exp. Ther., 166, 96-103 (1969) 
    21. Rohet, F., Rubat, C., Coudert, P., Albuisson, E., and Couquelet, J., Synthesis and trazodone-like analgesic activity of 4-phenyl-6-aryl-2-[3-(4-arylpiperazin-1-yl)propyl]pyridazin-3-ones. Chem. Pharm. Bull., 44, 980-986 (1996) 
    22. Santagati, N. A., Duro, F., Caruso, A., Trombadore, S., and Amico-Roxas, M., Synthesis and Pharmacological Study of A Series of 3(2H)-pyridazinones as Analgesic and Anti-inflammatory Agents. Farmaco, 40, 921-929 (1985) 
    23. Moreau, S., Coudert, P., Rubat, C., Albuisson, E., and Couquelet, J., Synthesis and peripherally acting analgesic 3- arylpiperazinyl-5-benzyl-pyridazines. Arzneim. Forsch./Drug Res., 46, 800-805 (1996) 
    24. Okun, R., Liddon, S. C., and Lasagnal, L., The effects of aggregation, electric shock, and adrenergic blocking drugs on inhibition of the 'writhing syndrome'. J. Pharmacol. Exp. Ther., 139, 107-114 (1963) 
    25. Okcelik, B., Unlu, S., Banoglu, E., Kupeli, E., Yesilada, E., and Sahin, M. F., Investigations of new pyridazinone derivatives for the synthesis of potent analgesic and anti-inflammatory compounds with cyclooxygenase inhibitory activity. Arch. Pharm., 336, 406-412 (2003) 
    26. Chintakunta, V. K., Akella, V., Vedula, M. S., Mamnoor, P. K., Mishra, P., Casturi, S. R., Vangoori, A., and Rajagopalan, R., 3-O-substituted benzyl pyridazinone derivatives as COX inhibitors. Eur. J. Med. Chem., 37, 339-347 (2002) 
    27. Meade, E. A., Smith, W. L., and DeWitt, D. L., Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by acetyl salicylic acid and other nonsteroidal anti-inflammatory drugs. J. Biol. Chem., 268, 6610- 6614 (1993) 
    28. Patrono, C. and Dunn, M. J., The clinical significance of inhibition of renal prostaglandin synthesis. Kidney Int., 32, 1- 12 (1987) 

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