Oxopyridinylquinoxaline derivative

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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544353, 544356, 544355, C07D24136, C07D24138, A01N 4360

Patent

active

056773056

ABSTRACT:
An oxopyridinylquinoxaline derivative represented by the following Formula I or pharmaceutically acceptable salts thereof: ##STR1## wherein R.sup.1 is hydrogen, halogen, nitro, or trihalomethyl; R.sup.2 is hydrogen, halogen, nitro, cyano, trihalomethyl, carbamoyl, carbamoyl substituted with lower alkyl, sulfamoyl, or sulfamoyl substituted with lower alkyl; R.sup.3 is hydrogen, nitro, or halogen; R.sup.4 is hydrogen, lower alkyl, substituted lower alkyl, lower cycloalkyl, or substituted lower cycloalkyl; R.sup.5 's are substituents independently selected from the group consisting of halogen, nitro, cyano, lower alkyl, carbamoyl, and carbamoyl substituted with lower alkyl; and n is an integer of 0 to 4. The derivative works as an antagonistic agent against both the NMDA receptors and the AMPA receptors, so that it is effective as a therapeutic agent for neurological disorders caused by excitatory amino acids binding to the receptors.

REFERENCES:
P. Birch et al., "6,7-Dinitro-quinoxaline-2,3-dion and 6-Nitro,7-cyano-quinoxaline-2,3-dion Antagonise Responses to NMDA in the Rat Spinal Cord via an Action at the Strychnine-Insensitive Glycine Receptor", Eur. J. Pharmacol., 156, pp. 177-180 (1988).
J. Drejer et al., "Glycine Reverses the Effect of HA-966 on NMDA Responses in Cultured Rat Cortical Neurons and in Chick Retina", Neurosci. Lett., 98, pp. 333-338 (1989).
E. Fletcher & D. Lodge, "Glycine Reverses Antagonism of N-Methyl-D-aspartate (NMDA) by 1-Hydroxy-3-aminopyrrolidone-2 *HA-966) but not by D-2-Amino-5-phophonovalerate (D-AP5) on Rat Cortical Slices", Eur. J. Pharmacol., 151, pp. 161-162 (1988).
T. Honore et al., "Quinoxalinediones: Potent Competitive Non-NMDA Glutamate Receptor Antagonists", Science, 241, pp. 701-703 (1988).
P. Jacobsen et al., "Quinoxalinediones as AMPA Receptor Antagonists: Mechanism and Structure-Activity Studies", Excitatory Amino Acid Receptors: Design of Agonists and Antagonists, pp. 246-259 (P. Krogsgaard-Larsen & J. Hansen eds., 1992).
J. Mosinger et al., "Blockade of Both NMDA and Non-NMDA Receptors Is Required for Optimal Protection Against Ischemic Neuronal Degeneration in the in Vivo Adult Mammalian Retina", Exp. Neurol., 113, pp. 10-17 (1991).
M. Sheardown et al., "A Potent Antagonist of the Strychnine Insensitive Glycine Receptor Has Anticonvulsant Properties", Eur. J. Pharmacol., 174, pp. 197-204 (1989).
M. Sheardown et al., "2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: A Neuroprotectant for Cerebral Ischemia", Science, 247, pp. 571-574 (1990).

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