Glycine receptor antagonists and the use thereof

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

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

A61K 31495

Patent

active

055146805

ABSTRACT:
Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, inducing anesthesia and treating psychosis are disclosed by administering to an animal in need of such treatment a compound having high affinity for the glycine binding site, lacking PCP side effects and which crosses the blood brain barrier of the animal.
Also disclosed are novel 1,4-dihydroquinoxaline-2,3-diones, and pharmaceutical compositions thereof. Also disclosed are highly soluble ammonium salts of 1,4-dihydroquinoxaline-2,3-diones.

REFERENCES:
patent: 3962440 (1976-06-01), St. Clair et al.
patent: 3992378 (1976-11-01), St. Clair et al.
patent: 4312807 (1982-01-01), Fuchs
patent: 4659713 (1987-04-01), Hass
patent: 4803270 (1989-02-01), Takemoto
patent: 4812458 (1989-03-01), Honore et al.
patent: 4889855 (1989-12-01), Jacobsen et al.
patent: 4912108 (1990-03-01), Jacobsen et al.
patent: 4948794 (1990-08-01), Honore et al.
patent: 4975430 (1990-12-01), Jahr et al.
patent: 4977155 (1990-12-01), Jacobsen et al.
patent: 4994460 (1991-02-01), Dextraze et al.
patent: 5026704 (1991-06-01), Honore et al.
patent: 5055465 (1991-10-01), Davey
patent: 5055470 (1991-10-01), Boissard et al.
patent: 5057516 (1991-10-01), Jacobsen et al.
patent: 5061706 (1991-10-01), Honoree et al.
patent: 5075306 (1991-12-01), Jacobsen et al.
patent: 5079250 (1992-01-01), Jacobsen et al.
patent: 5081123 (1992-01-01), Honore et al.
patent: 5109001 (1992-04-01), Jacobsen et al.
patent: 5166155 (1992-11-01), Jorgensen et al.
patent: 5187171 (1993-02-01), Cordi
patent: 5190941 (1993-03-01), Nozulak et al.
patent: 5196421 (1993-03-01), McQuaid et al.
patent: 5198461 (1993-03-01), Watjen et al.
patent: 5268378 (1993-12-01), Baker et al.
patent: 5283244 (1994-02-01), Sakamoto et al.
patent: 5308845 (1994-05-01), Honore et al.
patent: 5352683 (1994-10-01), Mayer et al.
Allison et al., Polyfluoroheterocyclic Compounds, Part XX. Preparation and Nucleophilic Substitution of Hexafluoroquinoxaline, J. Fluorine Chem. 1:59-667 (1971).
Burton et al., Halogeno-o-phenylenediamines and Derived Heterocycles. Part I. Reductive Fission of Benzotriazoles to o-Phenylenediamines, J. Chem. Soc. (C) 10:1268-1273 (1968).
Lutfy et al., Blockade of Morphine Tolerance by ACEA-1328, a novel NMDA receptor/glycine site antagonist, Eur. J. Pharmacol. 273:187-189 (Jan. 1995).
Warner et al., In Vivo Models of Cerebral Ischemia: Effects of Parenterally Administered NMDA Receptor Glycine Site Antagonists, J. Cereb. Blood Flow Metab. 15:188-196 (Mar. 1995).
Copy of the Supplementary Partial European Search Report, mailed by the European Patent Office on Aug. 10, 1995.
Derwent Abstract 93-387595 (Abstract of EP 572 852).
Adreasen et al., "Effects of Non-N-Methyl-D-Aspartate Antagonists on Synaptic Transmission in the In Vitro Rat Hippocampus", J. Physiol. 414:317-336 (1989).
Bigge, C., "Structural Requirements for the Development of Potent N-Methyl-D-Aspartic Acid (NMDA) Receptor Antagonists", Biochem. Pharm. 45:1547-1561 (1993).
Birch et al., "FG-9065 and FG-9041 antagonise responses to NMDA via an action at the strychnine-insensitive glycine receptor", Meeting of the British Pharmacological Society, Nottingham, England, Sep. 7-9, 1988, Br. J. Pharmacol. 95:758P (1988).
Carling et al., "Anticonvulsant Activity of Glycine-site NMDA Antagonists", Bioorganic & Medicinal Chem. Lett. 3:65-70 (1993).
Carling et al., "3-Nitro-3,4-dihydro-2(1H)-quinolones. Excitatory Amino Acid Antagonists Acting at Glycine-Site NMDA and (RS)-.alpha.-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors", J. Med. Chem. 36:3397-3408 (1993).
Cheeseman, G. W. H., "Quinoxalines and Related Compounds, Part VI. Substitution of 2,3-Dihydroxyquinoxaline and its 1,4-Dimethyl Derivative", J. Chem. Soc. 223:1170-1176 (1962).
Davies & Collingridge, "Quinoxalinediones as Excitatory Amino Acid Antgonists in the Vertebrate Central Nervous System", Int. Rev. Neurobiol. 32:281-303 (1990).
Drejer & Honore, "New quinoxalinediones show potent antagonism of quisqualate responses in cultured mouse cortical neurons", Neur. Lett. 87:104-108 (1988).
Fletcher et al., "Quinoxalinediones selectively block quisqualate and kainate receptors and synaptic events in rat neocortex and hippocampus and frog spinal cord in vitro", Br. J. Pharmacol. 95:585-597 (1988).
Frenk et al., "Absence of Side-Effects in the Anticonvulsant Action of Cortically Applied Antagonists of N-Methyl-D-Aspartate", Brain Res. 373:222-226 (1986).
Hays et al., "N-Sulfonyl Derivatives of 6,7-Dichloro 3,4-Dihydro-3-Oxo-quinoxalinecarboxylate as Glycine-site NMDA and AMPA Antagonists", Bioorg. & Med. Chem. Lett. 3:77-80 (1993).
Honore et al., "Quinoxalinediones: Potent Competitive Non-NMDA Glutamate Receptor Antagonists", Science 241:701-703 (Aug. 5, 1988).
Honore et al., "Quinoxalinediones Non-N-Methyl-D-aspartate Receptor Antagonists as Potential Drug Candidates", pp. 451-460, in: Excitatory Amino Acids, Meldrum et al. (eds.), Raven Press Ltd., New York (1991).
Horner et al., "Derivatives of quinoxaline as isosteres of the pteridines", Chem. Abst. 48:2692 (1953).
Kay & Ikeda, "The quinoxalinediones antagonise the visual firing of sustained retinal ganglion cells", Eur. J. Pharmacol. 164:381-384 (1989).
Kemp & Leeson, "The glycine site of the NMDA receptor-five years on", TiPS 14:20-25 (Jan. 1993).
Kessler et al., "Quinoxaline derivatives are high-affinity antagonists of the NMDA receptor-associated glycine sites", Brain Res. 489:377-382 (1989).
Kessler et al., "A Glycine Site Associated with N-Methyl-D-Aspartic Acid Receptors: Characterization and Identification of a New Class of Antagonists", J. Neurochem. 52:1319-1328 (1989).
Kleckner & Dingledine, "Selectivity of Quinoxalines and Kynurenines as Antagonists of the Glycine Site on N-Methyl-D-aspartate Receptors", Mol. Pharmacol. 36:430-436 (1989).
Leeson et al., "Kynurenic Acid Derivatives. Structure-Activity Relationships for Excitatory Amino Acid Antagonism and Identification of Potent and Selective Antagonists at the Glycine Site on the N-Methyl-D-aspartate Receptor", J. Med. Chem. 34:1243-1252 (1991).
Leeson et al., "Amino Acid Bioisosteres: Design of 2-Quinolone Derivatives as Glycine-Site N-Methyl-D-aspartate Receptor Antagonists", Bioorg. & Med. Chem. Lett. 3:299-304 (1993).
Leeson, P., "Glycine-Site N-Methyl-D-Aspartate Receptor Antagonists", pp. 339-381, in: Drug Design for Neurosci., Kozikowski (ed.), Raven Press Ltd., New York (1993).
Lester et al., "Interaction of 6-Cyano-7-nitroquinoxaline-2,3-dione with the N-Methyl-D-aspartate Receptor-Associated Glycine Binding Site", Mol. Pharmacol. 35:565-570 (1989).
Littman et al., "The quinoxalinediones DNQX, CNQX and two related congeners suppress hair cell-to-auditory nerve transmission", Hearing Res. 40:45-53 (1989).
Lodge & Jones, "Evidence for Glutamate Receptor Subtypes From In Vivo Electrophysiology: Studies with HA-966, Quinoxalinediones and Philanthotoxin", pp. 101-108 in: Excitatory Amino Acids and Neuronal Plasticity, Ben-Ari, Y. (ed.), Plenum Press, New York (1990).
Lodge et al., "Excitatory amino acids:new tools for old stories or Pharmacological subtypes of glutamate receptors:electrophysiological studies", Can. J. Physiol. Pharmacol. 69:1123-1128 (1991).
Louvet et al., "Novel benzimidazoles as ligands for the strychnine-insensitive N-methyl-D-aspartate-linked glycine receptor", Eur. J. Med. Chem. 28:71-75 (1993).
McFarlane & Smith, "A New Route to N-Hydroxyquinoxaline-2,3-diones and some AZA-Analogues", Tetrahedron Lett. 28:6363-6366 (1987).
McQuaid et al., "Synthesis and Excitatory Amino Acid Pharmacology of a Series of Heterocyclic-Fused Quinoxalinones and Quinazolinones", J. Med. Chem. 35:3319-3324 (1992).
Moore et al., "Anticonvulsant Activity of Glycine-Site NMDA Antagonists",

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Glycine receptor antagonists and the use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Glycine receptor antagonists and the use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Glycine receptor antagonists and the use thereof will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-1227424

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.