Abstract
A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure-activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K(+) channel. Preferred compounds were subsequently evaluated for selectivity in an alpha(1)-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.
MeSH terms
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Benzocycloheptenes / chemical synthesis*
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Benzocycloheptenes / chemistry
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Benzocycloheptenes / pharmacology
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Cell Line
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Neurotransmitter Agents / chemical synthesis*
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Neurotransmitter Agents / chemistry
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Neurotransmitter Agents / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / metabolism
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Structure-Activity Relationship
Substances
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Benzocycloheptenes
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Ether-A-Go-Go Potassium Channels
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KCNH1 protein, human
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NR2B NMDA receptor
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Neurotransmitter Agents
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Pyridines
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Receptors, N-Methyl-D-Aspartate