YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis of Aryloxyallylthiopyridazine Derivatives

Aryloxyallylthiopyridazine 유도체 합성

  • 권순경 (덕성여자대학교 약학대학) ;
  • 김미경 (덕성여자대학교 약학대학)
  • Published : 2002.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Allylthio group of the sulfur compounds of garlic oil plays an important role for prevention and treatment of hepatic diseases induced by toxic substances or carbon tetrachloride. Thus allylthio group as pharmacologically active group was introduced into pyridazine heterocycle ring. Aryloxyallylthiopyridazine derivatives were synthesized and their hepatoprotective activities were screened in rat. The activities of these compounds were weaker than alkoxyallylthiopyridazine derivatives, which exhibit a superior hepatoprotective effect.

Keywords

References

  1. Dorant, E., Brandt, P. A., Goldbolm, R. A., Hermus, R.J. J.and Sturmans, F. : Garlic and its singnificance for the prevention of cancer in humans; a critical view. Br. J. Cancer 67, 424 (1993)
  2. Sparnins, V. L., Barany, G. and Wattenberg, L. W. : Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse. Carcinogenesis 9(1), 131 (1988).
  3. Hayes, M. A., Rushmore, T.H. and Goldberg, M. T. : Inhibition of hepatocarcinogenic responses to 1,2-dimethylhydrazine by diallyl sulfide, a component of garlic oil. Carcinogenesis 8(8), 1155 (1987)
  4. Dausch, J. G. and Nixon, D. W. : Garlic: A review of its relationship to malignant disease. Preventive Medicine 19, 346 (1990)
  5. Wargovich, M. J., Woods, C., Eng, V. W. S., Stephens, L. C. and Gray, K. : Chemopre-vention of N-nitrosomethylbenzylarnine-induced esophageal cancer in rats by the naturally occurring thioether, diallyl sulfide. Cancer Res. 48, 6872 (1988)
  6. Kim, B. H. and Lee, Y. S. : Study on the inhibitory effect of diallysulfide and/or diallyldisulfide in the rat hepatocarcino-genesis. J. Appl. pharmcol, 3, 279 (1995)
  7. Rawls, R. : Turning on carcinogens. C & EN. p. 31 (Oct. 7. 1996)
  8. Kim, S. G. and Novak, R. E : The induction of Cytochrome P450 2E1 by nitrogen-and sulfur-containing heterocycles: Expression and molecular regulation. Toxicol. appl. pharmacol, 120, 257 (1993)
  9. Prous, J. R. : Chemoprotective agents. The years drug news. 1995, 631 (1995)
  10. Kim, S. G., Chung, H. J. and Cho, J. Y. : Molecular mechanism of alkyl sulfide-modulated carbon tetrachloride-induced hepatotoxicity: The role of cytochrome $P_{450}$ $2E_{1}$ , P450 2B and glutathione S-transferase expression. J. pharmacol. exp. Ther. 277, 1058 (1996)
  11. Kwon, S. K., Lee, E. B., Kim, M. K. and Park, Y. N. : Synthesis of allylthiopyridazine derivatives and hepatoprotective activities. Duksung Bull. Pharm. Sci. 9, 3 (1998)
  12. Tisler, M and Stanovnik, B. : Pyridazine. Advances in heterocyclic chemistry edited by A. R. Katritzky and A. J. Boulton, Academic Press, vol. 9, 211 (1968)
  13. Drueg, J. : Pyridazine in der Azneimittelsynthese, Angew. Chem. 70, 5 (1958)
  14. Drueg, J., Meier, Kd. and Eichenberger, K. : Heilmittelchemische Studien in der heterocyclischen Reihe, Pyridazine I. Derivate der cyclischen Maleinsaeureund Citraconsaeure hydrazids. Helv. Chem. Acta. 37, 121 (1954)
  15. Kocevar, M., Sranovnik, B. and Tisler, M. : Heterocycles, CI. Syntheses and Isomerizations of some allylthio nitrogen heterocycles. Croatica Chemica 45, 457 (1973)
  16. Mizzoni, R. H. and Spoerri, P. E. : Synthesis in the pyridazine series. I. J. Am. Chem. Soc. 73, 1873 (1951) https://doi.org/10.1021/ja01148a537