Novel Alkylaminopyridazine Derivatives: Synthesis and Their Anti-proliferative Effects against MCF-7 Cells

  • Kim, Chaewon ;
  • Park, Eun-Hee ;
  • Park, Myung-Sook
  • Received : 2013.07.22
  • Accepted : 2013.08.22
  • Published : 2013.11.20


A series of new 3-alkylamino-6-allylthio-pyridazine derivatives was synthesized through allythiolation and amino-de-halogenation and were expected to have anti-proliferative activity. 6-Allylthio-3-chloropyridazine was prepared from the reaction of 3,6-dichloropyridazine with allylmercaptan and sodium hydroxide. The alkylamines such as methylamine and the dialkylamines such as dimethylamine were introduced into the 3-position of the pyridazine ring. These new compounds showed anti-proliferative activities against MCF-7 human breast cancer cells in CCK-8 assays. These compounds are thus promising candidates for chemotherapy of breast cancer. Two compounds, 14 and 15, showed higher potencies for inhibiting growth of breast cancer cells than did 5FU. This suggests the potential anti-proliferative activity of these compounds.


Alkylaminopyridazines;Dialkylaminopyridazines;Allylthiopyridazines;Human breast cancer;MCF-7


  1. Tisler, M.; Stanovnik, B. Advances in Heterocyclic Chemistry; Katritzky & Boulton., Eds.; 1984; Vol. 3, pp 1-56.
  2. Uto, Y.; Ueno, Y.; Kiyotsuka, Y.; Miyazawa, T.; Kurata, H.; Ogata, T.; Tagaki, T.; Wakimoto, S.; Ohsumi, Euro. J. Med. Chem. 2011, 46, 1892.
  3. Grey, R.; Pierce, A. C.; Bemis, G.; Jacobs, M. D.; Moody, C. S.; Jajoo, R.; Mohal, N.; Green, J. Bioorg. Med. Chem. Lett. 2009, 19, 3019.
  4. Kandile, N. G.; Mohamed, M. I.; Zaky, H.; Mohamed, H. M. Euro. J. Med. Chem. 2009, 44, 1989.
  5. Bradbury, R. H.; Hales, N.; Rabow, A.; Walker, G. E.; Acton, D. G.; Andrews, D. M.; Ballard, P.; Brooks, N. A. N.; Colclough, N.; Girdwood, A.; Hancox, U.; Jones, O.; Jude, D.; Loddick, S. A.; Mortlock, A. A. Bioorg. Med. Chem. Lett. 2011, 21, 5442.
  6. Contreras, J. M.; Parrot, I.; Sippl, W.; Rival, Y. M.; Wermuth, C. G. J. Med. Chem. 2001, 44, 2707.
  7. Parrot, I.; Wermuth, C. G.; Hibert, M. Tetrahedron Lett. 1999, 40, 7975.
  8. Wermuth, C. G.; Bourguignon, J.; Schlewer, G.; Gies, J.; Schoenfelder, A.; Melikian, A.; Bouchet, M. J. Med. Chem. 1987, 30, 239.
  9. Shin, H. S.; Kwon, S. K. Arch. Pharm. Res. 2003, 5, 351.
  10. Wermuth, C. G.; Schlewer, G.; Bourguignon, J. J.; Maghiros, G.; Bouchet, M. J., Moire, C.; Kan, J. P.; Worms, P.; Biziere, K. J. Med. Chem. 1989, 32, 528.
  11. Kleemann, A.; Engel, J. Pharmaceutical Substances; 2001, 4th, pp 1340-1342.
  12. Contreras, J. M.; Rival, Y. M.; Chayer, S.; Bourguignon, J. J.; Wermuth, C. G. J. Med. Chem. 1999, 42, 730.
  13. Lee, J. I.; Park, H.; Yun, Y. S.; Kwon, S. K. J. Kor. Chem. Soc. 2001, 45, 386.
  14. Kwon S. K.; Kim, M. K. Yakhak Hoeji 2002, 46, 89.
  15. Kwon, S. K. Yakhak Hoeji 2002, 46, 155.
  16. Kwon, S. K.; Moon, A. R. Arch. Pharm. Res. 2005, 4, 391.
  17. Park, E. H.; Park, M. S. Yakhak Hoeji 2005, 49(1), 56.
  18. Kwon, S. K.; Lee, M. S. Yakhak Hoeji 2005, 49(6), 505.
  19. Park, E. H.; Park, M. S. J. Korean Chem. Soc. 2007, 51, 244.
  20. Lee, M. S.; Kim, E. S.; Moon, A.; Park, M. S. Bull. Korean Chem. Soc. 2009, 30, 83.
  21. Won, Y. H.; Park, M. S. Arch. Pharm. Res. 2010, 33, 189.
  22. Parrot, I.; Rival, Y.; Wermuth, C. G. Synthesis 1999, 7, 1163.
  23. Lu, Z.; Twieg, R. J. Tetrahedron 2005, 61, 903.
  24. Scheele, U.; Dechert, S.; Meyer, F. Tetrahedron Lett. 2007, 48, 8366.
  25. Akkaoui, A. E.; Koubachi, J.; Kazzouli, S. W.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Tetrahedron Lett. 2008, 49, 2472.
  26. Tewari, A.; Hein, M.; Zapt, A.; Beller, M. Tetrahedron 2005, 61, 9705.
  27. Yokoyama, R.; Ito, S.; Okujima, T.; Kubo, T.; Yasunami, M.; Tajiri, A.; Morita, N. Tetrahedron 2003, 59, 8191.
  28. Yoon, D. H.; Ji, M. K.; Ha, H. J.; Park, J.; Kang, P.; Lee, W. K. Bull. Korean Chem. Soc. 2013, 34, 1899.
  29. Li, X.; Zheng, S. L.; Li, X.; Li, J. L.; Qiang, O.; Liu, R.; He, L. J. Eur. J. Med. Chem. 2012, 54, 42.

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