Synthesis and anti-inflammatory activity of certain piperazinylthienylpyridazine derivatives
Tóm tắt
In this study, a novel series of 2-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones(3a- f), 2-(4-substituted piperazin-l-yl carbonylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones(4a- c) and 2-[2-(4-substituted piperazin-l-ylcarbonylethyl)]-6-(thien-2-yl)-2H-pyridazin-3-ones(5a,b) were prepared from 6-(thien-2-yl)-2H- pyridazin-3-one(1). In addition, 3-(4-substituted piperazin-l-ylcarbonyl methyl thio)-6-(thien-2-yl) pyridazines(6a- c) and 3-[2-(4-substitutedpiperazin-l-ylcarbonyl ethylthio]-6-(thien-2-yl) pyridazines(7a,b) were synthesized. Furthermore, 5-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones(12a,b) were prepared. The structures of the new compounds were confirmed by elemental analysis as well as by1H-NMR,IR andMS data. Some of the newly prepared compounds were subjected to evaluation for their anti-inflammatory activity against carrageenan-induced paw edema at a dose of 10 mg/kg using indomethacin as the reference standard.
Tài liệu tham khảo
Banoglu, E., Akoglu, C., Unlu, S., Kupeli, E., YesilActa, E., and Sahin, M. F., Amide derivatives of [6-(5-methyl-3-phenyl-pyrazol-1-yl)-3(2H)-pyridazinone-2-yl] acetic acids as potential analgesic and anti-inflammatory compounds.Arch. Pharm. Pharm. Med. Chem., 337, 7–14, (2004).
Bianchi, M., Butti, A., Christidis, Y, Perronnet, J., Barzaghi, F., Cesana, R., and Nencioni, A., Gastric anti-secretory, anti-ulcer and cytoprotective properties of substituted (E)-4-phenyl- and heteroaryl-4-oxo-2-butenoic acids.Eur. J. Med. Chem., 23, 45–52 (1988).
Close, W. J., Burris, D., Tiffany, D., and Spielman, M. A., The analgesic activity of some benzoxazolinone derivatives.J. Am. Chem. Soc., 71, 1265–1268 (1949).
Coates, W. J. and Mckillop, A., One-pot preparation of 6-substituted 3(2H)-pyridazinones from ketones.Synthesis, 3, 334–342(1993).
Contreras, J., Parrot, I., Sippl, W., Rival, Y. M., and Wermuth, C. G., Design, synthesis and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors.J. Med. Chem., 44, 2707–2718(2001).
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).
Dal Piaz, V., Vergelli, C., Giovannoni, P., Scheideier, M. A., Petrone, G., and Zaratin, P., 4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups and related compounds: synthesis and antinociceptive activity.Farmaco, 58, 1063–1070(2003).
Dogruer, D. S., Sahin, M. F., Unlu, S., and Ito, S., Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity.Arch. Pharm. Pharm. Med. Chem., 333, 79–86 (2000).
Kalgutkar, A. S., Marnett, A. B., Crews, B. C., Remmel, R. P., and Marnett, L J., Ester and amide derivatives of the non-steroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors.J. Med. Chem., 43, 2860–2870 (2000).
Nakamura, H., Shimoda, A., Ishii, K., and Kadokawa, T., Central and peripheral analgesic action of non-acidic non-steroidal anti-inflammatory drugs in mice and rats.Arch. Int. Pharmacodyn., 282, 16–25 (1986).
Onkol, T, Dogruer, D. S., Ito, S., and Sahin, M. F., Synthesis and antinociceptive activity of (5-chloro-2-benzothiazolinon-3-yl) acetamide derivatives.Arch. Pharm. Pharm. Med. Chem., 333, 337–340 (2000).
Onkol, T, Ito, S., Yildirim, E., Erol, K., and Sahin, M. F., Synthesis and antinociceptive activity of (2-benzazolon-3-yl) propionamide derivatives.Arch. Pharm. Pharm. Med. Chem., 334, 17–20(2001).
Onkol, T, Sahin, M. F., Yildirim, E., Erol, K., and Ito, S., Synthesis and antinociceptive activity of (5-chloro-2(3H)-benzoxazolon-3-yl) propanamide derivatives.Arch. Pharm. Res., 27, 1086–1092 (2004a).
Onkol, T., Yildirim, E, Erol, K., Ito, S., and Sahin, M. F., Synthesis and antinociceptive activity of (5-chloro-2(3H)-benzothiazolinone-3-yl) propanamide derivatives.Arch. Pharm. Pharm. Med Chem., 337, 475–481 (2004b).
Ravina, E., Teran, C., Dominguez, N. G., and Masaguer, C. F., Synthesis and antihypertensive activity of 6-(2-thienyl)-5-aminomethyl-3-hydrazinopyridazines.Arch. Pharm., 324, 455–459(1991).
Renard, P., Lesieur, D., Lespagnol, C., Cazin, M., Brunet, C., and Cazin, J. C., Acyl-6-benzoxazolinones et acides (acyl-6-oxo-2-benzoxazolinyl-3) alcanoiqines.Eur. J. Med. Chem., Chim. Ther., 15, 453–456 (1980).
Sahin, M. F., Badicoglu, B., Cokce, M., Kupeli, E., and YesilActa, E., Synthesis and analgesic and anti-inflammatory activity of methyl 6-substituted 3(2H)-pyridazinon-2-yl acetate derivatives.Arch. Pharm. Pharm. Med. Chem., 337, 445–452 (2004).
Takaya, M., Sato, M., Terashima, K., Tanizawa, H., and Maki, Y., 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).
Unlu, S., Baytas, S. N., Kupeli, E., and YesilActa, E., Studies on 7-acyl-5-chloro-2-oxo-3H-benzoxazole derivatives as potential analgesic and anti-inflammatory agents.Arch. Pharm. Pharm. Med. Chem., 336, 310–321 (2003).
Viaud, M. C., Jamoneau, P., Flouzat, C., Espiard, J. G. B., Pfeiffer, B., Renard, P., Caignard, D. H., Actam, G., and Guillaumet, G., N-Substituted oxazolo[5,4-b]pyridine-2(1H)-ones: A new class of non-opiate antinociceptive agents. J.Med. Chem., 38, 1278–1286 (1995).
Winter, C. A., Risley, E. A., and Nuss, G. W., Carrageenin-induced oedema in hind paw of the rat as an assay for anti-inflammatory drugs.Proc. Soc. Exp. Boil. Med., 111, 544–547 (1962).
Zayed, S. M., El-Namaky, H. M., and Moti, F. M. A., Synthesis of biologically active S-(6-arylpyridazin-3-yl)thioglycolic acids and related derivatives.Indian J. Chem., 16B, 936–938 (1978).
Zayed, M. F., Ali, A. S., and El-Din, N. K., Photosensitized oxygenation of 6-aryl-2,3-dihydro-3-mercaptopyridazines and 2,6-diaryl-2,3-dihydro-pyridazine-3-thiones.Sulfur lett., 12, 215–221 (1991).