Synthesis of Potential Anticancer 6-Allylthio-3-aminopyridazine Derivatives

잠재적 항암작용이 있는 6-Allylthio-3-aminopyridazine 유도체의 합성

  • Published : 2007.06.20


A series of new 6-allylthio-3-aminopyridazine derivatives was synthesized through allylthiolation, amination and expected for anti-tumor activity. The pyridazine nucleus was obtained by condensing hydrazine monohydrate with maleic anhydride. 3,6-Dichloropyridazine was synthesized from 3,6-dihydroxypyridazine by treating with POCl3. 6-Allylthio-3-chloropyridazine was prepared from the reaction of 3,6-dichloropyridazine with allylmercaptan and sodium hydroxide. The heterocycles with nitrogen nucleophile such as morpholine, piperazine, pyrazole, imidazole, pyrrolidine, piperidine, perhydroazepine, and perhydroazocine were introduced into 3-position of pyridazine ring. The substitution reaction of 6-allylthio-3-chloropyridazine with heteroamines was performed by refluxing for 24~48 h in n-buthanol with NH4Cl.




  1. Tisler, M.; Stanovnik, B. Advances in heterocyclic chemistry; Katritzky & Boulton., Ed.; 1984; Vol. 3, pp.1-56
  2. Contreras, J. M.; Parrot, I.; Sippl, W.; Rival, Y. M.; Wermuth, C.G. J. Med. Chem., 2001, 44, 2707
  3. Parrot, I.; Wermuth, C. G.; Hibert, M. Tetrahedron Lett. 1999, 40, 7975
  4. Wermuth, C. G.; Bourguignon, J.; Schlewer, G.; Gies, J.; Schoenfelder, A.; Melikian, A.; Bouchet, M. J. Med. Chem., 1987, 30, 239
  5. Shin H.S.; Kwon, S. K. Arch. Pharm. Res., 2003, 5, 351
  6. 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
  7. Kleemann, A.; Engel, J. Pharmaceutical Substances; 2001, 4th, pp.1340-1342
  8. Contreras, J. M.; Rival, Y. M.; Chayer, S.; Bourguignon, J. J.; Wermuth, C. G. J. Med. Chem., 1999, 42, 730
  9. Lee, J. I.; Park, H.; Yun, Y. S.; Kwon, S. K. J. Kor. Chem. Soc., 2001, 45, 386
  10. Kwon S. K.; Kim, M.K.; Yakhak Hoeji, 2002, 46, 89
  11. Kwon, S.K. Yakhak Hoeji, 2002, 46, 155
  12. Kwon, S. K.; Moon, A. R. Arch. Pharm. Res., 2005, 4, 391
  13. Park, E. H.; Park, M. S. Yakhak Hoeji, 2005, 49(1), 56
  14. Kwon, S. K.; Lee, M. S. Yakhak Hoeji, 2005, 49(6), 505
  15. Parrot, I.; Rival, Y.; Wermuth, C. G.; Synthesis, 1999, 7, 1163
  16. Lu, Z.; Twieg, R. J. Tetrahedron, 2005, 61, 903
  17. Eldrup, A. B.; Dahl, O.; Nielsen, P. J. Am. Chem. Soc. 1997, 119, 11116
  18. Beletskaya, I.; Bessmertnykh, G.; Guilard, R. Tetrahedron Lett., 1999, 40, 6393
  19. Tewari, A.; Hein, M.; Zapt, A.; Beller, M. Tetrahedron, 2005, 61, 9705
  20. Yokoyama, R.; Ito, S.; Okujima, T.; Kubo, T.; Yasunami, M.; Tajiri, A.; Morita, N.; Tajiri, A.; Morita, N. Tetrahedron, 2003, 59, 8191

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