Abstract
The synthesis of a series of 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl-2-arylbenzofuran and 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran-2-carboxamide derivatives as novel alpha(2C)-adrenergic receptor antagonists are described. Their affinity at three different human alpha(2)-adrenergic receptors is reported, and some of these compounds exhibited high affinity for the alpha(2C)-adrenergic receptor with high subtype selectivity. Among them, compound 10e has been found to show the anti-L-dopa-induced dyskinetic activity in marmosets. The structure-activity relationship of these compounds is also discussed.
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists*
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / pharmacology*
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Animals
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Benzofurans / chemical synthesis*
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Benzofurans / pharmacology*
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Callithrix
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Dopamine Agents / pharmacology
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Dyskinesia, Drug-Induced / physiopathology
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Humans
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Indicators and Reagents
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Isoquinolines / chemical synthesis*
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Isoquinolines / pharmacology*
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Levodopa / antagonists & inhibitors
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Levodopa / pharmacology
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Receptors, Adrenergic, alpha-2
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Structure-Activity Relationship
Substances
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4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran
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ADRA2C protein, human
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Antagonists
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Benzofurans
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Dopamine Agents
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Indicators and Reagents
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Isoquinolines
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Receptors, Adrenergic, alpha-2
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Levodopa