Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-06-01
2000-09-26
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514292, 544126, 546 82, C07D47104, C07D41712, A61K 315375, A61K 314375
Patent
active
061242853
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel indole-2,3-dione-3-oxime derivatives capable of antagonising the effect of excitatory amino acids, such as glutamate. The invention also relates to a method of preparing the chemical compounds of the invention, to pharmaceutical compositions comprising the chemical compounds, and a method of treatment herewith.
BACKGROUND ART
Excessive excitation by neurotransmitters can cause the degeneration and death of neurones. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA), glutamate and aspartate, at the N-methyl-D-aspartate (NMDA), the alfa-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, and the kainate receptor. This excitotoxic action is responsible for the loss of neurones in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or haemorrhagic stroke, cerebral vasospasm, hypoglycaemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from near-drowning, pulmonary surgery and cerebral trauma as well as lathyrism, Alzheimer's, and Huntington's diseases. Compounds capable of blocking excitatory amino acid receptors are therefore considered useful for the treatment of the above disorders and diseases, as well as Amyotrophic Lateral Sclerosis (ALS), schizophrenia, Parkinsonism, epilepsy, anxiety, pain and drug addiction.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide novel indole-2,3-dione-3-oxime derivatives which are excitatory amino acid antagonists and useful in the treatment of disorders or diseases of mammals, including humans, which are responsive to excitatory amino acid receptor antagonists.
Accordingly, in its first aspect, the invention provides the novel indole-2,3-dione-3-oxime derivatives described in claim 1.
In another aspect the invention relates to the use of a chemical compound of the invention for the preparation of a pharmaceutical composition.
In a third aspect the invention provides a pharmaceutical composition comprising a therapeutically effective amount of the chemical compound of the invention together and a pharmaceutically acceptable excipient, carrier or diluent.
In a fourth aspect the invention relates to the use of a chemical compound of the invention for the manufacture of a pharmaceutical composition for the treatment of a disorder or disease of a mammal, including a human, which disorder or disease is responsive to glutamic and/or aspartic acid receptor antagonists.
In a more specific aspect the invention relates to the use of a chemical compound of the invention for the manufacture of a pharmaceutical composition for the treatment a cerebrovascular disorder, lathyrism, Alzheimer's disease, Huntington's diseases, amyotrophic lateral sclerosis (ALS), schizophrenia, Parkinsonism, epilepsy, anxiety, pain or drug addiction.
In a fifth aspect the invention provides a method of treating disorders or diseases of living animals, including humans, which are responsive to excitatory amino acid receptor antagonists, comprising administering to a living animal body, including a human, in need thereof an effective amount of a chemical compound of the invention.
In a more specific aspect the invention provides a method of treating a cerebrovascular disorder, lathyrism, Alzheimer's disease, Huntington's diseases, amyotrophic lateral sclerosis (ALS), schizophrenia, Parkinsonism, epilepsy, anxiety, pain or drug addiction.
In a sixth aspect the invention relates to the use of the chemical compound of the invention in a method of treating a disorder or disease of a mammal, including a human, which disorder or disease is responsive to glutamic and/or aspartic acid receptor antagonists, said method comprising administering to a living animal body, including a human, in need thereof an effective amount of the chemical compound.
In a more specific aspect the invention relates to the use of the chemical compound of the
REFERENCES:
patent: 5801174 (1998-09-01), Moldt et al.
patent: 5917053 (1999-06-01), Moldt et al.
JPET, Nielsen et al., vol. 289(3), pp. 1492-1501, 1999.
Drejer Jorgen
Watjen Frank
NeuroSearch A/S
Rotman Alan L.
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