Abstract
Novel 3-cyanoisoquinoline Kv1.5 antagonists have been prepared and evaluated in in vitro and in vivo assays for inhibition of the Kv1.5 potassium channel and its associated cardiac potassium current, IKur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency, selectivity, and oral bioavailability.
MeSH terms
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Administration, Oral
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Animals
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Anti-Arrhythmia Agents / chemical synthesis*
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Anti-Arrhythmia Agents / chemistry
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Anti-Arrhythmia Agents / pharmacology
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Atrial Fibrillation / drug therapy*
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Biological Availability
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Electrophysiology
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Heart / drug effects
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Heart / physiology
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Humans
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Kv1.5 Potassium Channel / antagonists & inhibitors*
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Kv1.5 Potassium Channel / physiology
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology
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Patch-Clamp Techniques
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Rats
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-Arrhythmia Agents
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Isoquinolines
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Kv1.5 Potassium Channel
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Nitriles