Abstract
A series of diphenyl-substituted heterocycles were synthesized and evaluated by electrophysiological techniques as openers of the cloned mammalian large-conductance, Ca(2+)-activated potassium (maxi-K) channel. The series was designed from deannulation of known benzimidazolone maxi-K opener NS-004 (2) thereby providing an effective template for obtaining structure-activity-related information. The triazolone ring system was the most studied wherein 4,5-diphenyltriazol-3-one 6d (maxi-K = 158%) was identified as the optimal maxi-K channel opener.
MeSH terms
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Animals
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Crystallography, X-Ray
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In Vitro Techniques
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Large-Conductance Calcium-Activated Potassium Channels
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Models, Molecular
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Molecular Conformation
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Oocytes / drug effects
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Oocytes / physiology
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Patch-Clamp Techniques
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Potassium Channels, Calcium-Activated / agonists*
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Potassium Channels, Calcium-Activated / physiology
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
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Xenopus laevis
Substances
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4-(5-chloro-2-hydroxyphenyl)-5-(3,5-bis(trifluoromethyl)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one
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Large-Conductance Calcium-Activated Potassium Channels
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Potassium Channels, Calcium-Activated
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Triazoles