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The Pharmaceutical Society of Korea (대한약학회)
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Synthesis and Antinociceptive Activity of (5-Chloro-2(3H)-Benzoxazolon-3-yl) Propanamide Derivatives

  • Onkol, Tijen (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University) ;
  • Sahin, M.Fethi (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University) ;
  • Yidirim, Engin (Department of Pharmacology, Faculty of Medicine, Osmangazi University) ;
  • Erol, Kevser (Department of Pharmacology, Faculty of Medicine, Osmangazi University) ;
  • Ito, Shigero (Institute for Medicinal and Dental Engineering, Tokyo Medicinal and Dental University)
  • Published : 2004.11.01
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Abstract

In this study, (5-chloro-2(3H)-benzoxazolon-3-yl)propanamide derivatives were synthesized. The chemical structures of the compounds were elucidated by their IR and $^1H-NMR$ spectral data and microanalysis. The compounds were tested for anti nociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods. The varying levels of anti nociceptive activity of the compounds were compared with those of dipyrone and aspirin. Among these compounds, compound 5e, 5g, and 5h have been found to be significantly more active than the others and the standards in all the tests.

Keywords

References

  1. Aguirre-Banuelos, P. and Granados-Soto, V., Peripheral antinociceptive interaction of dipyrone and morphine in the formalin test. Proc.West. Pharmacol. Soc., 43, 11-14 (2000)
  2. Akman, H., Aksu, F., Gultekin, I., Ozbek, H., Oral, U., Doran, F., and Baysal, F., A possible central antinociceptive effect of dipyrone in mice. Pharmacology, 53, 71-78 (1996) https://doi.org/10.1159/000139417
  3. Bannwarth, B., Demotes-Mainard, F., Schaeverbeke, T., Labat, L., and Dehais, J., Central analgesic effects of aspirin-like drugs, Fundam. Clin. Pharmacol., 9, 1-7 (1995) https://doi.org/10.1111/j.1472-8206.1995.tb00258.x
  4. Biancchi, C. and Franceschini, J., Experimental observations on Haffners method for testing analgesic drugs. Br. J. Pharmacol., 9, 280-284 (1954)
  5. 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) https://doi.org/10.1021/ja01172a036
  6. Dajani, E. Z., Larsen, K. R., Taylor, J., Dajani, N. E., Shahwan, T. G., Neelemen, S. D., Taylor, M. S., Dayton, M. T., and Mir, G. N., 1',1'-Dimethylheptyl-$\Delta$-8-tetrahydrocannabinol-11-oic Acid: A Novel, Orally effective cannabinoid with analgesic and anti-inflammatory properties. J. Pharmacol. Exp. Ther., 291, 31-38 (1999)
  7. 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) https://doi.org/10.1016/S0223-5234(96)80008-0
  8. Dal Piaz, V., Vergelli, C., Giovannoni, P., Scheideler, M. A., Petrone, G., and Zaratin, P., 4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups ans related compounds:synthesis and antinociceptive activity. Farmaco, 58, 1063-1070 (2003) https://doi.org/10.1016/S0014-827X(03)00162-9
  9. D'Amour, F. E. and Smith, D. L., A method for determining loss of pain sensation. J. Pharmacol. Exp. Ther., 72, 74-79 (1941)
  10. 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)
  11. Dundar, Y., Cakir, B., Erol, K., and Sahin, M. F., Studies on the synthesis and antinociceptive activity of 1-[4-(2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)butanoyl]-4-aryl or alkyl substituted piperazine derivatives. J. Fac. Pharm. Gazi, 20, 21-30 (2003)
  12. Eddy, N. B. and Leimbach, D., Synthetic analgesic (II). Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. Exp. Ther., 107, 385-393 (1953)
  13. Flouzat, C., Bresson, Y., Mattio, A., Bonnet, J., and Guillaumet, G., Novel nonopioid non-antiinflammatory analgesic: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones. J. Med. Chem., 36, 497-503 (1993) https://doi.org/10.1021/jm00056a010
  14. Fujii, K., Studies on the syntheses of phenothiazine derivatives(V). Syntheses of pyrido[3,2,1-kh]phenothiazine derivatives (I). J. Pharm. Soc. Japan, 77, 1065-1068 (1957)
  15. Gulcan, H. O., Kupeli, E., Unlu, S., Yesilada, E., and Sahin, M. F., 4-(5-Chloro-2(3H)-benzoxazolon-3-yl) butanoic acid derivatives: synthesis, antinociceptive and anti-inflammatory properties, Arch. Pharm. Pharm. Med. Chem., 336, 477-482 (2003) https://doi.org/10.1002/ardp.200300722
  16. Kalgutkar, A. S., Marnett, A. B., Crews, B. C., Remmel, R. P., and Marnett, L. J., Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors. J. Med. Chem., 43, 2860-2870 (2000) https://doi.org/10.1021/jm000004e
  17. Koster, R., Anderson, M., and Beer, E. J., Acetic acid for analgesic screening. Fed. Proc., 18, 412 (1959)
  18. Lespagnol, C., Cazin, M., Cazin, J. C., Lesieur, D., and Dupont, C., Recherches sur lactivite analgesique de derives de la benzoxazolinone. Chim. Ther., 2, 347-348 (1967)
  19. Noble, F., Smadja, C., and Roques, B. P., Role of endogenous cholecystokinin in the facilitation of mu-mediated anti-nociception by delta-opioid agonists. J. Pharmacol. Exp. Ther., 271, 1127-1134 (1994)
  20. 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)
  21. Onkol, T., Dogruer, D. S., Sahin, M. F., and Ito, S., Synthesis and antinociceptive activity of (5-chloro-2-benzothiazolon-3-yl)acetamide derivatives. Pharm. Pharm. Med. Chem., 333, 337-340 (2000) https://doi.org/10.1002/1521-4184(200010)333:10<337::AID-ARDP337>3.0.CO;2-A
  22. Onkol, T., Ito, S., Yildirin, 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) https://doi.org/10.1002/1521-4184(200101)334:1<17::AID-ARDP17>3.0.CO;2-Z
  23. Onkol, T., Dundar, Y., Sirmaqul, B., Erol, K., and Sahin, M. F., (2-Oxobenzazoline-3-yl)alkanoic acide derivatives and antinociceptive activity. J. Fac. Pharm. Gazi, 19, 15-24 (2002)
  24. Palaska, E., Unlu, S., Erdooan, H., Safak, C., Gumusel, B., and Sunal, R., 1-(3-Methyl-2-benzoxazolinone-6-yl)-2-(4-substituted piperazine-1-yl)ethanones and ethanols: analgesic and antiinflammatory activities. Eur. J. Med. Chem., 28, 963-967 (1963) https://doi.org/10.1016/0223-5234(93)90052-G
  25. 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., 15, 453-456 (1980)
  26. 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-morpholino3(2H)-pyridazinone and related compounds. J. Med. Chem., 22, 53-58 (1979) https://doi.org/10.1021/jm00187a013
  27. Safak, C., Erdooan, H., Palaska, E.. Sunal, R., and Duru, S., Synthesis of 3-(2-pyridylethyl)benzoxazolinone derivatives:Potent analgesic and antiinflammatory compounds inhibiting prostaglandin $E_2$. J. Med. Chem., 35, 1296-1299 (1992) https://doi.org/10.1021/jm00085a018
  28. Unlu, S., Onkol, T., Okcelik, B., Kupeli, E., Yesilada, E., and Sahin, M. F., Synthesis and antinociceptive activities of 1-(3methyl-2-benzoxazolinone-6-yl)-2-aminoethanones and ethanoles. J. Fac.Pharm. Gazi, 19, 79-85 (2002)
  29. Viaud, M. C., Jamoneau, P., Flouzat, C., Bizot-Espiard, J. G., Pfeiffer, B., Renard, P., Caignard, D. H., Adam, G., and Guillaumet, G., N-Substituted oxazolo[5,4-b]pyridin-2(1H)-ones:A new class of non-opiate antinociceptive agents. J. Med. Chem., 38, 1278-1286 (1995) https://doi.org/10.1021/jm00008a006
  30. Zinner, V. H., Randow, F., and Wigert, H., Benzazoles. XXI. (Benzoxazolon-3-yl) carboxylic acids. J. Prakt. Chem., 33, 130-138 (1966) https://doi.org/10.1002/prac.19660330303