Abstract
A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM.
MeSH terms
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Animals
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Dogs
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / drug effects*
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Heart Rate / drug effects
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Humans
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Indicators and Reagents
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Mice
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Naphthalenes / chemical synthesis
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Naphthalenes / pharmacology*
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Piperazines / chemical synthesis
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Piperazines / pharmacology*
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Potassium Channel Blockers / pharmacology*
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Receptors, Somatostatin / antagonists & inhibitors*
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Weight Loss / drug effects
Substances
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Indicators and Reagents
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KCNH2 protein, human
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MCHR1 protein, human
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Naphthalenes
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Piperazines
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Potassium Channel Blockers
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Receptors, Somatostatin
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aminomethyl tetrahydronaphthalene ketopiperazine