Regiospecific one-pot, combinatorial synthesis of new substituted pyrimido[4,5-c]pyridazines as potential monoamine oxidase inhibitors

New 3-aryl-6-methylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones and 3-aryl-6-ethyl-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazin-5(6H)-ones were efficiently synthesized via a regiospecific one-pot reaction of N-methylbarbituric acid and N-ethyl-2-thiobarbituric acid with various arylglyoxal monohydrates in the presence of hydrazine dihydrochloride in ethanol at 50 °C. The target compounds were obtained in high yields and were regioisomerically pure after recrystallization. These new heterocycles may act as potential MAO_{B} inhibitors.

Regiospecific one-pot, combinatorial synthesis of new substituted pyrimido[4,5-c]pyridazines as potential monoamine oxidase inhibitors

New 3-aryl-6-methylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones and 3-aryl-6-ethyl-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazin-5(6H)-ones were efficiently synthesized via a regiospecific one-pot reaction of N-methylbarbituric acid and N-ethyl-2-thiobarbituric acid with various arylglyoxal monohydrates in the presence of hydrazine dihydrochloride in ethanol at 50 °C. The target compounds were obtained in high yields and were regioisomerically pure after recrystallization. These new heterocycles may act as potential MAO_{B} inhibitors.

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  • D¨omling, A. Chem. Rev. 2006, 106, 17–89.
  • Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471–1499.
  • Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51–80.
  • Montagne, C.; Shiers, J. J.; Shipman, M. Tetrahedron Lett. 2006, 47, 9207–9209.
  • Pokhodylo, N. T.; Matiychuk, V. S.; Obushak, M. D. J. Comb. Chem. 2009, 11, 481–485.
  • Ghahremanzadeh, R.; Sayyafi, M.; Ahadi, S.; Bazgir, A. J. Comb. Chem. 2009, 11, 393–396.
  • Zhang, L.; Lushington, G. H.; Neuenswander, B.; Hershberger, J. C.; Malinakova, H. C. J. Comb. Chem. 2008, 10, 285–302.
  • Tu, S. J.; Zhang, X. H.; Han, Z. G.; Cao, X. D.; Wu, S. S.; Yan, S.; Hao, W. J.; Zhang, G.; Ma, N. J. Comb. Chem. 2009, 11, 428–432.
  • Wang, X. S.; Li, Q.; Wu, J. R.; Tu, S. J. J. Comb. Chem. 2009, 11, 433–437.
  • Zhu, J.; Bienayme, H. Multicomponent Reactions; Wiley-VCH: Weinheim, Germany, 2005.
  • Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168–3210.
  • Shaabani, A.; Seyyedhamzeh, M.; Maleki, A.; Behnam, M.; Rezazadeh, F. Tetrahedron Lett. 2009, 50, 2911–2913. 13.Adib, M.; Sheibani, E.; Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron 2008, 64, 10681–10686.
  • Sunderhaus, J. D.; Martin, S. F. Chem. Eur. J. 2009, 15, 1300–1308. 15.Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439–4486.
  • Maes, B. U. W.; Lemi`ere, G. L. F. In Comprehensive Heterocyclic Chemistry III ; Katritzky, A. R., Ramsden, C.
  • [Chem. Abstr. 1989, 110, 75541]. 21.Preshin, G. N.; Sherbakova, L. I.; Zykova, T. N.; Sokolova, V. N. Farmakol. Tokisikol. 1971, 35, 466–471. 22.Sacchi, A.; Laneri, S.; Arena, F.; Abignente, E.; Gallitelli, M.; D’amico, M.; Filippelli, W.; Rossi, F. Eur. J. Med.
  • Chem. 1999, 34, 1003–1008. 23.Nagawade, R. R.; Khanna, V. V.; Bhagwat, S. S.; Shinde, D. B. Eur. J. Med. Chem. 2005, 40, 1325–1330. 24.Liljebris, C.; Martinsson, J.; Tedenborg, L.; Williams, M.; Barker, E.; Duffy, J. E. S.; Nygren, A.; James, S. Bioorg.
  • Med. Chem. Lett. 2002, 12, 3497–3504. 25.Grey, R.; Pierce, A. C.; Bemis, G. W.; Jacobs, M. D.; Moody, C. S.; Jajoo, R.; Mohal, N.; Green, J. Bioorg. Med.
  • Chem. Lett. 2009, 19, 3019–3022. 26.Brown, D. J. in Comprehensive Heterocyclic Chemistry, Katritzky, A. R.; Rees, C. W. Eds.; Pergamon Press:
  • Oxford, UK, 1984; Vol. 3, pp. 57–155. 27.Wamhoff, H.; Dzenis, J.; Hirota, K. Adv. Heterocycl. Chem. 1992, 55, 129–259. 28.Hamilton, G. A. in Progress in Bioorganic Chemistry, Kaiser, E. T.; Kezdy, F. J. Eds.; Wiley: New York, NY,
  • Geha, R. M.; Rebrin, I.; Chen, K.; Shih, J. C. J. Biol. Chem. 2001, 276, 9877–9882.
  • Westlund, K. N.; Denney, R. M.; Kochersperger, L. M.; Rose, R. M.; Abell, C. W. Science 1985, 230, 181–183.
  • Bach, A. W. J.; Lan, N. C.; Johnson, D. L.; Abell, C. W.; Bembenek, M. E.; Kwan, S.W.; Seeburg, P. H.; Shih, J.
  • C. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 4934–4938.
  • Grimsby, J.; Chen, K.; Wang, L. J.; Lan, N. C.; Shin, J. C. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 3637–3641.
  • Rimaz, M.; Rabiei, H.; Khalili, B.; Prager, R. H. Aust. J. Chem. 2014, 67, 283–288.
  • Rimaz, M.; Mousavi, H. Turk. J. Chem. 2013, 37, 252–261. 39.Khalafy, J.; Rimaz, M.; Ezzati, M.; Prager, R. H. Bull. Korean. Chem. Soc. 2012, 33, 2890–2896.
  • Khalafy, J.; Rimaz, M.; Panahi, L.; Rabiei, H. Bull. Korean. Chem. Soc. 2011, 32, 2428–2432. 41.Rimaz, M.; Khalafy, J. Arkivoc 2010, (ii ), 110–117.
  • Rimaz, M.; Khalafy, J.; Najafi Moghadam, P. Aust. J. Chem. 2010, 63, 1396–1401.
  • Rimaz, M.; Khalafy, J.; Noroozi Pesyan, N.; Prager, R. H. Aust. J. Chem. 2010, 63, 507–510.
  • Pesyan, N. N.; Khalafy, J.; Rimaz, M. Curr. Chem. Lett. 2013, 2, 177–186.
  • Khalafy, J.; Rimaz, M.; Rabiei, H.; Panahi, L. J. Sulfur Chem. 2013, 34, 395. 46.Eftekhari-Sis B.; Zirak M.; Akbari A. Chem. Rev. 2013, 113, 2958–3040.
  • Riley H. A., Gray A. R. Gray, Organic Syntheses; Wiley & Sons: New York, NY, USA, 1943; Collect. Vol. II, p. 509.
  • Rimaz, M.; Noroozi Pesyan, N.; Khalafy, J. Magn. Reson. Chem. 2010, 48, 276–285.
Turkish Journal of Chemistry-Cover
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