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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

Abstract

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.

Keywords

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

References

  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. https://doi.org/10.1016/j.ejmech.2011.02.002
  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. https://doi.org/10.1016/j.bmcl.2009.04.061
  4. Kandile, N. G.; Mohamed, M. I.; Zaky, H.; Mohamed, H. M. Euro. J. Med. Chem. 2009, 44, 1989. https://doi.org/10.1016/j.ejmech.2008.09.047
  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. https://doi.org/10.1016/j.bmcl.2011.06.122
  6. Contreras, J. M.; Parrot, I.; Sippl, W.; Rival, Y. M.; Wermuth, C. G. J. Med. Chem. 2001, 44, 2707. https://doi.org/10.1021/jm001088u
  7. Parrot, I.; Wermuth, C. G.; Hibert, M. Tetrahedron Lett. 1999, 40, 7975. https://doi.org/10.1016/S0040-4039(99)01533-6
  8. Wermuth, C. G.; Bourguignon, J.; Schlewer, G.; Gies, J.; Schoenfelder, A.; Melikian, A.; Bouchet, M. J. Med. Chem. 1987, 30, 239. https://doi.org/10.1021/jm00385a003
  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. https://doi.org/10.1021/jm00123a004
  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. https://doi.org/10.1021/jm981101z
  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. https://doi.org/10.5012/jkcs.2007.51.3.244
  20. Lee, M. S.; Kim, E. S.; Moon, A.; Park, M. S. Bull. Korean Chem. Soc. 2009, 30, 83. https://doi.org/10.5012/bkcs.2009.30.1.083
  21. Won, Y. H.; Park, M. S. Arch. Pharm. Res. 2010, 33, 189. https://doi.org/10.1007/s12272-010-0201-x
  22. Parrot, I.; Rival, Y.; Wermuth, C. G. Synthesis 1999, 7, 1163.
  23. Lu, Z.; Twieg, R. J. Tetrahedron 2005, 61, 903. https://doi.org/10.1016/j.tet.2004.11.017
  24. Scheele, U.; Dechert, S.; Meyer, F. Tetrahedron Lett. 2007, 48, 8366. https://doi.org/10.1016/j.tetlet.2007.09.099
  25. Akkaoui, A. E.; Koubachi, J.; Kazzouli, S. W.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Tetrahedron Lett. 2008, 49, 2472. https://doi.org/10.1016/j.tetlet.2008.02.008
  26. Tewari, A.; Hein, M.; Zapt, A.; Beller, M. Tetrahedron 2005, 61, 9705. https://doi.org/10.1016/j.tet.2005.06.067
  27. Yokoyama, R.; Ito, S.; Okujima, T.; Kubo, T.; Yasunami, M.; Tajiri, A.; Morita, N. Tetrahedron 2003, 59, 8191. https://doi.org/10.1016/j.tet.2003.08.048
  28. Yoon, D. H.; Ji, M. K.; Ha, H. J.; Park, J.; Kang, P.; Lee, W. K. Bull. Korean Chem. Soc. 2013, 34, 1899. https://doi.org/10.5012/bkcs.2013.34.6.1899
  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. https://doi.org/10.1016/j.ejmech.2012.04.019

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