Abstract
A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D(2) ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D(2) partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D(2) affinity, function, and SRI activity.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Antipsychotic Agents / chemical synthesis
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Antipsychotic Agents / chemistry*
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Antipsychotic Agents / therapeutic use
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Disease Models, Animal
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Dopamine Agonists / chemical synthesis
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Dopamine Agonists / chemistry*
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Dopamine Agonists / therapeutic use
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Quinolones / chemical synthesis
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Quinolones / chemistry*
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Quinolones / therapeutic use
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Receptor, Serotonin, 5-HT1A / chemistry
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Receptor, Serotonin, 5-HT1A / metabolism
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D2 / metabolism
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Schizophrenia / drug therapy*
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Selective Serotonin Reuptake Inhibitors / chemical synthesis
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Selective Serotonin Reuptake Inhibitors / chemistry*
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Selective Serotonin Reuptake Inhibitors / therapeutic use
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Structure-Activity Relationship
Substances
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Antipsychotic Agents
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Dopamine Agonists
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Quinolones
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Receptors, Dopamine D2
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Serotonin Uptake Inhibitors
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Receptor, Serotonin, 5-HT1A