Abstract
The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.
MeSH terms
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Animals
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Antidepressive Agents / chemical synthesis
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Antidepressive Agents / chemistry*
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Antidepressive Agents / pharmacology
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Antidepressive Agents / therapeutic use*
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Cell Line
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Depression / drug therapy*
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Humans
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Male
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Molecular Docking Simulation
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Quinolines / therapeutic use*
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Rats
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Rats, Wistar
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Receptors, Glucocorticoid / antagonists & inhibitors*
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Receptors, Glucocorticoid / metabolism
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Structure-Activity Relationship
Substances
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Antidepressive Agents
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Quinolines
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Receptors, Glucocorticoid