Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo.

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 20, 1999, Pages 2921-2926

  Jimonet, Patrick ^a   Boireau, Alain ^a   Chevé, Michel ^a   Damour, Dominique ^a   Genevois Borella, Arielle ^a   Imperato, Assunta ^a   Pratt, Jeremy ^a   Randle, John C R ^a   Ribeill, Yves ^a   Stutzmann, Jean Marie ^a   Mignani, Serge ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMPA RECEPTOR; AMPA RECEPTOR ANTAGONIST; GLYCINE RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PYRAZINE DERIVATIVE;

ANTICONVULSANT ACTIVITY; ARTICLE; BINDING SITE; DRUG ANTAGONISM; DRUG SYNTHESIS; IN VITRO STUDY; IN VIVO STUDY; INTRAPERITONEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; ISOMER; MOUSE; NONHUMAN; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING SITES; EXCITATORY AMINO ACID ANTAGONISTS; GLYCINE; MICE; PYRAZINES; RECEPTORS, AMPA; RECEPTORS, N-METHYL-D-ASPARTATE; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033581566     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00502-8     Document Type: Article

References (20)

1. For a review, see : Lodge, D.; Collinridge, G. Eds. The pharmacology of excitatory amino acids. A special report. Trends in Pharmacological Sciences 1991.
2. Bradford, H. F. Progress in Neurobiology, 1995, 47, 477 and references cited therein.
3. a) Bigge, C. F.; Nikam, S. S. Exp. Opin. Ther. Patents, 1997, 7, 1099
4. b) Guzikowski, A. P.; Xiong Cai, S.; Espitia, S. A.; Hawkinon, J. E.; Huettner, J. E.; Nogales, D. F.; Tran, M.; Woodward, R. M.; Weber, E.; Keana, J. F. J. Med. Chem., 1996, 39, 4643
5. c) Di Fabio, R.; Capelli, A. M.; Conti, N.; Cugola, A.; Donati, D.; Feriani, A.; Gastaldi, P.; Gaviraghi, G.; Hewkin, C. T.; Micheli, F.; Missio, A.; Mugnaini, M.; Pecunioso, A.; Quaglia, A. M.; Ratti, E.; Rossi, L.; Tedesco, G.; Trist, D. G.; Reggiani, A. J. Med. Chem., 1997, 40, 841.
6. Ohmori, J.; Sakamoto, S.; Kubota, H.; Shimizu-Sasamata, M.; Okada,m.; Kawasaki, S.; Hidaka, K.; Togami, J.; Furuya, T.; Murase, K. J. Med. Chem., 1994, 37, 467.
7. Turski, L.; Huth, A.; McDonald, F.; Schneider, H. H.; Neuhaus, R.; Dyrks, T.; Bresink, I.; Ottow, E. 27th Annual Meeting of the Society for Neuroscience, New Orleans, October 25-30, 1997, poster # 946.18.
8. Ornstein, P. L.; Arnold, M. B.; Augenstein, N. K. J. Med. Chem., 1993, 36, 2046.
9. Woodward, R. M.; Huettner, J. E.; Guastella, J.; Keana, J. F.; Weber, E. Mol. Pharmacol., 1995, 47, 568 and references cited therein.
10. Di Fabio, R.; Capelli, A. M.; Conti, N.; Cugola, A.; Donati, D.; Feriani, A.; Gastaldi, P.; Gaviraghi, G.; Hewkin, C. T.; Micheli, F.; Missio, A.; Mugnaini, M.; Pecunioso, A; Quaglia, A. M.; Ratti, E.; Rossi, L.; Tedesco, G.; Trist, D. G.; Reggiani, A., J. Med. Chem. Lett., 1997, 40, 841.
11. 1H-NMR, IR and mass spectroscopy, and have given satisfactory combustion analyses (C, H, N)
12. b) Aloup, J-C.; Barreau, M.; Damour, D.; Jimonet, P.; Genevois-Borella, A.; Mignani, S.; Ribeill, Y. Patent Applications WO 95/02601, Chem. Abstr. 122: 314575;
13. WO 95/26350, Chem. Abstr. 124: 146198
14. and WO 96/14318, Chem. Abstr. 125: 114701.
15. Mignani, S.; Aloup, J-C.; Blanchard, J-C.; Böhme, G. A.; Boireau, A.; Damour, D.; Debono, M- W.; Dubroeucq, M-C.; Genevois-Borella, A.; Imperato, A.; Jimonet, P.; Pratt, J.; Randle, J. C. R.; Reibaud, M.; Ribeill, Y.; Stutzmann, J-M. Drug Dev. Res., 1999, submitted for publication.
16. Hosomi, A.; Sakata, Y.; Sakurai, H. Chem. Lett., 1984, 1117 and references cited therein.
17. Honoré, T.; Drejer, J. J. Neurochem., 1988, 51, 457
18. b) Canton., T.; Doble, A.; Miquet, J-M; Jimonet, P.; Blanchard, J-C. J. Pharm. Pharmacol., 1992, 44, 812.
19. Swinyard, E. A.; Brown, W. C.; Goodmann, L. S. J. Pharmacol. Exp. Ther., 1952, 106, 319.
20. 50 values are defined as the dose which protected 50% of the animals from a tonic convulsion (6 male CD1 mice/dose of compound, with at least 3 doses plus 1 group receiving vehicle alone.