Abstract
Phenethyl aminoheterocycles like compound 1 were known to be potent I(Kur) blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.
Keywords:
AERP; Atrial fibrillation; I(Kur); K(V)1.5; Phenethylamine.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
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Amines / chemical synthesis
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Amines / chemistry
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Amines / pharmacology*
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Animals
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Blood Pressure / drug effects
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Cyclohexanes / chemistry
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Cyclohexanes / pharmacology
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Dose-Response Relationship, Drug
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Humans
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Kv1.5 Potassium Channel / antagonists & inhibitors*
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Kv1.5 Potassium Channel / metabolism
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Mice
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Molecular Structure
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Potassium Channel Blockers / chemical synthesis
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Potassium Channel Blockers / chemistry
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Potassium Channel Blockers / pharmacology*
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Rabbits
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Rats
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Amines
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Cyclohexanes
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Kv1.5 Potassium Channel
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Potassium Channel Blockers
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Spiro Compounds