First synthesis of important secondary oxidative metabolites of morphine and codeine with the Michael addition

• Autorzy: Sándor Garadnay , Zsuzsanna Gyulai , Sándor Makleit , Attila Sipos
• Języki publikacji: EN

Abstrakty

EN

Abstract Morphine (1) and codeine (2) are two representatives of medically important, frequently used natural opiates, therefore the exploration of their metabolic pathways and the exact characterization of the metabolites are main targets of their pharmacological studies. These morphinans also play a crucial role in drug abuse; therefore, the analysis and preparation of the metabolites for identification and quantitation in human samples are considered important aims. In order to allow the in-depth analysis of metabolites derived from the oxidative pathways through morphinone (3) and codeinone (4), synthetic procedures have been elaborated for the gram-scale preparation of glutathione and N-acetylcysteine adducts. Primary pharmacological studies revealed the inactive nature of these metabolites in opioid receptor binding tests. Graphical abstract [...]

Słowa kluczowe

EN

Morphine; Codeine; Metabolite; Glutathione; Cysteine

• Czasopismo: Open Chemistry
• Rocznik: 2013
• Tom: 11
• Numer: 3
• Strony: 430-437

Daty

wydano

2013-03-01

online

2012-12-28

Twórcy

autor

Sándor Garadnay

• Department of Organic Chemistry, University of Debrecen, H-4032, Debrecen, Hungary

autor

Zsuzsanna Gyulai

• Department of Organic Chemistry, University of Debrecen, H-4032, Debrecen, Hungary

autor

Sándor Makleit

• Department of Organic Chemistry, University of Debrecen, H-4032, Debrecen, Hungary

autor

Attila Sipos

• Department of Pharmaceutical Chemistry, Medical and Health Science Center, University of Debrecen, H-4032, Debrecen, Hungary,

Bibliografia

• [1] J.V. Aldrich, S.C. Vigil-Cruz, Narcotic Analgesics. In: Burger’s Medicinal Chemistry and Drug Discovery (John Wiley & Sons, New York, 2003) 329
• [2] M.H. Levy, New Engl. J. Med. 335, 1124 (1996) http://dx.doi.org/10.1056/NEJM199611143352011[Crossref]
• [3] L.A. Woods, J. Pharm. Exp. Therap. 112, 158 (1954)
• [4] Y. Kumagi, T. Tokdaka, S. Toki, J. Pharm. Exp. Therap. 255, 504 (1990)
• [5] B.J. Canning, Pulmon. Pharmacol. Ther. 22, 75 (2009) http://dx.doi.org/10.1016/j.pupt.2009.01.003[Crossref]
• [6] T. Ishida, Y. Kumagai, Y. Ikeda, K. Ito, M. Yano, S. Toki, K. Mihasni, T. Fujioka, Y. Iwase, S. Hachiyama, Drug Metabol. Dispos. 17, 77 (1989)
• [7] M. Jairaj, D.G. Watson, M.H. Grant, G.G. Skellern, Chem.-Biol. Interactions 146, 121 (2003) http://dx.doi.org/10.1016/S0009-2797(03)00091-7[Crossref]
• [8] T. Ishida, M. Yano, S. Toki, J. Anal. Toxicol. 22, 567 (1998) [Crossref]
• [9] T. Ishida, Y. Kumagai, Y. Ikeda, K. Ito, S. Yano, S. Hachiyama, Org. Mass Spectroscopy 24, 286 (1989) http://dx.doi.org/10.1002/oms.1210240418[Crossref]
• [10] S. Yamano, E. Kageura, T. Ishida, S. Toki, J. Biol. Chem. 260, 5259 (1985)
• [11] S. Yamano, A. Takahashi, T. Todaka, S. Toki, Xenobiotica 27, 645 (1997) http://dx.doi.org/10.1080/004982597240244[Crossref]
• [12] J.F. Bickley, A. Ciucci, P. Evans, S.M. Roberts, N. Rossa, M.G. Santoro, Bioorg. Med. Chem. 12, 3221 (2004) http://dx.doi.org/10.1016/j.bmc.2004.03.061[Crossref]
• [13] S.P. Findlay, L.F. Small, J. Am. Chem. Soc. 72, 3247 (1950) http://dx.doi.org/10.1021/ja01163a126[Crossref]
• [14] H. Rapoport, D.R. Baker, H.N. Reist, J. Org. Chem. 22, 1489 (1957) http://dx.doi.org/10.1021/jo01362a044[Crossref]
• [15] T. Sagara, M. Okamura, Y. Shimohigashi, M. Ohno, K. Kanematsu, Bioorg. Med. Chem. Lett. 14, 1609 (1995) http://dx.doi.org/10.1016/0960-894X(95)00263-S[Crossref]
• [16] A. Sipos, L. Girán, H. Mittendorfer, H. Schmidhammer, S. Berényi, Tetrahedron 64, 1023 (2008) http://dx.doi.org/10.1016/j.tet.2007.08.075[Crossref]
• [17] M. Tóth, Zs. Gyulai, S. Berényi, A. Sipos, Lett. Org. Chem. 4, 539 (2007) http://dx.doi.org/10.2174/157017807782795538[Crossref]
• [18] A. Sipos, S. Berényi, Monatsh. Chemie 140, 387 (2009) http://dx.doi.org/10.1007/s00706-008-0038-x[Crossref]
• [19] L. Girán, S. Berényi, A. Sipos, Tetrahedron 64, 10388 (2008) http://dx.doi.org/10.1016/j.tet.2008.08.069[Crossref]
• [20] E.J. Corey, I. Szekely, C.S. Shiner, Tetrahedron Lett. 18, 3529 (1977) http://dx.doi.org/10.1016/S0040-4039(01)83284-6[Crossref]
• [21] J.O. Polazzi, R.N. Schut, M.P. Kotick, J. Med. Chem. 23, 174 (1980) http://dx.doi.org/10.1021/jm00176a013[Crossref]
• [22] M.P. Kotick, D.L. Leland, J.O. Polazzi, R.N. Schut, J. Med. Chem. 23, 166 (1980) http://dx.doi.org/10.1021/jm00176a012[Crossref]
• [23] A.D. Becke, J. Chem. Phys. 98, 5648 (1993) http://dx.doi.org/10.1063/1.464913[Crossref]
• [24] A.D. Becke Physical Reviews. A 38, 3098 (1988) http://dx.doi.org/10.1103/PhysRevA.38.3098[Crossref]
• [25] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37, 785 (1988) http://dx.doi.org/10.1103/PhysRevB.37.785[Crossref]
• [26] S.H. Vosko, L. Wilk, M. Nusair, Can. J. Phys. 58, 1200 (1980) http://dx.doi.org/10.1139/p80-159[Crossref]
• [27] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery, Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople Gaussian 03, Revision C.02, (Gaussian, Inc., Wallingford CT, 2004)

Identyfikatory

DOI

10.2478/s11532-012-0181-4