Abstract
A novel series of 2-(3-indolyl)alkylamino-1-(3-chlorophenyl)ethanols was prepared and evaluated for in vitro ability to stimulate cAMP production in Chinese hamster ovary cells expressing cloned human beta(3)-AR. The optically active 30a was found to be the most potent and selective human beta(3)-AR agonist in this series with an EC(50) value of 0.062nM. In addition, 30a selectivity for human beta(3)-AR was 210-fold and 103-fold that for human beta(2)-AR and beta(1)-AR, respectively. Furthermore, 30a showed potent agonistic activity at rat beta(3)-AR.
MeSH terms
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Adrenergic beta-3 Receptor Agonists*
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Adrenergic beta-Agonists / chemical synthesis*
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Adrenergic beta-Agonists / pharmacology*
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Alkanes / chemical synthesis*
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Alkanes / pharmacology*
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Animals
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CHO Cells
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Cloning, Molecular
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Cricetinae
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Cyclic AMP / metabolism
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Ethanolamines / pharmacology
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Humans
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Indoles / pharmacology*
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Models, Molecular
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Molecular Conformation
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Rats
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Structure-Activity Relationship
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Tryptamines / chemical synthesis
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Tryptamines / pharmacology
Substances
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Adrenergic beta-3 Receptor Agonists
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Adrenergic beta-Agonists
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Alkanes
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Ethanolamines
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Indoles
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Tryptamines
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BRL 37344
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Cyclic AMP