Abstract
The combination of I(Kr) and I(Ks) blockade could lead to synergistic and safe class III anti-arrhythmic effect with the enhanced efficacy and reduced risk. On the rationale of structural hybridization of azimilide and HMR-1556, a novel series of I(Kr) and I(Ks) dual blockers were designed, synthesized and evaluated in vitro. One compound, 3r (CPUY11018), deserves further evaluation for its potent anti-arrhythmic activity and favorable cardiovascular profile.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Arrhythmia Agents / chemical synthesis*
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Anti-Arrhythmia Agents / pharmacology
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Chromans / chemical synthesis*
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Chromans / chemistry
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Chromans / pharmacology
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Drug Evaluation, Preclinical / methods
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Guinea Pigs
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Heart Rate / drug effects
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Heart Rate / physiology
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / physiology
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Nucleic Acid Hybridization
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Potassium Channel Blockers / chemical synthesis*
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Voltage-Gated / antagonists & inhibitors*
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Potassium Channels, Voltage-Gated / physiology
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Rats
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Rats, Sprague-Dawley
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Anti-Arrhythmia Agents
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Chromans
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HMR 1556
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Potassium Channel Blockers
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Potassium Channels, Voltage-Gated
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Sulfonamides
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potassium channel protein I(sk)