Abstract
Diphenylphosphinic amides and diphenylphosphine oxides have been synthesized and tested as inhibitors of the Kv1.5 potassium ion channel as a possible treatment for atrial fibrillation. In vitro structure-activity relationships are discussed and several compounds with Kv1.5 IC(50) values of <0.5 μM were discovered. Selectivity over the ventricular IKs current was monitored and selective compounds were found. Results from a rabbit PD-model are included.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Biphenyl Compounds / chemistry
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Humans
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Inhibitory Concentration 50
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Kv1.5 Potassium Channel / antagonists & inhibitors*
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Molecular Structure
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Oxides / chemical synthesis*
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Oxides / chemistry
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Oxides / pharmacology*
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Phosphines / chemical synthesis*
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Phosphines / chemistry
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Phosphines / pharmacology*
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Phosphinic Acids / chemistry
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Protein Binding / drug effects
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Rabbits
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Structure-Activity Relationship
Substances
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(2-isopropyl-5-methylcyclohexyl) diphenylphosphine oxide
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Amides
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Biphenyl Compounds
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Kv1.5 Potassium Channel
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Oxides
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Phosphines
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Phosphinic Acids
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diphenyl