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Amino acid derivatives of substituted quinexaline 2,3-dione derivatives as glutamate receptor antagonists

A technology of quinoxaline and amino, which is applied in the fields of compounds of Group 5/15 elements of the periodic table, metabolic diseases, drug combinations, etc., and can solve problems such as no disclosure or prompting

Inactive Publication Date: 2003-10-29
WARNER-LAMBERT CO
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The application does not disclose or suggest compounds having the amino groups of the present invention as substituents, or the necessary methods for their preparation

Method used

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Embodiment Construction

[0033] The substituted quinoxaline-2,3-diones of the present invention are those represented by formula I or pharmaceutically acceptable salts thereof: Wherein R is an amino acid derivative;

[0034] n is an integer of 1-4;

[0035] R 1 is hydrogen, alkyl, aralkyl, carboxyalkyl, phosphoroalkyl, or phosphonoalkyl;

[0036] R 2 is hydrogen, hydroxyl, or amino;

[0037] R 3 and R 4 each independently hydrogen, alkyl, cycloalkyl, alkenyl, halogen, haloalkyl, nitro, cyano, SO 2 CF 3 , C(O)R 6 , where R 6 for hydroxyl, alkoxy, Alkyl, haloalkyl, aryl, aralkyl, CH 2 SO 2 R 6 , (CH 2 ) m CO 2 R 9 , where R 9 is hydrogen, alkyl, aralkyl or cycloalkyl, (CH 2 ) m CONR 7 R 8 , (CH 2 ) m SO 2 NR 7 R 8 , or NHCOR 6 , where m is an integer of 0-4, R 7 and R 8 each independently hydrogen, alkyl, cycloalkyl, haloalkyl, or aralkyl;

[0038] R 5 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, halogen, haloalkyl, aryl, heteroaralkyl, aralkyl, heteroaryl, nitro, ...

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Abstract

A novel series of substituted quinoxaline 2,3-diones useful as neuroprotective agents are taught. Novel intermediates, processes of preparation, and pharmaceutical compositions containing the compounds are also taught. The compounds are glutamate antagonists and are useful in the treatment of stroke, cerebral ischemia, or cerebral infarction resulting from thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia, Alzheimer's, Parkinson's, and Huntington's diseases.

Description

Background of the invention [0001] The present invention relates to novel glutamate receptor antagonists, which are novel compounds of the 5,6,7,8-substituted quinoxaline 2,3-dione type. The a or b position of the fused ring system is replaced by an amino acid derivative. The compound is an excitatory amino acid receptor antagonist acting on glutamate receptors, including N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors such as α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) receptor and kainate receptor or either. The present invention also relates to the use of these quinoxaline-2,3-diones as neuroprotective agents for the treatment of conditions caused by various phenomena such as thromboembolic or hemorrhagic stroke, cerebral vasospasm, hypoglycemia, cardiac arrest, status epilepticus, Cerebral ischemia or cerebral infarction caused by peripartum asphyxia, hypoxia (such as due to drowning), lung surgery and brain injury, etc., can also be used in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D241/44C07F9/6509C07C229/18A61K31/495A61P3/08A61P9/00A61P9/06A61P25/00A61P25/04A61P25/08A61P25/18A61P25/20A61P25/28C07C229/14C07C229/20
CPCC07C229/14C07D241/44C07F9/650994A61P25/00A61P25/04A61P25/08A61P25/18A61P25/20A61P25/28A61P3/08A61P9/00A61P9/06
Inventor S·尼卡姆
Owner WARNER-LAMBERT CO
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