Human iPSC-derived cardiomyocytes and pyridyl-phenyl mexiletine analogs.
Bioorg Med Chem Lett
; 46: 128162, 2021 08 15.
Article
em En
| MEDLINE
| ID: mdl-34062251
ABSTRACT
In the United States, approximately one million individuals are hospitalized every year for arrhythmias, making arrhythmias one of the top causes of healthcare expenditures. Mexiletine is currently used as an antiarrhythmic drug but has limitations. The purpose of this work was to use normal and Long QT syndrome Type 3 (LQTS3) patient-derived human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to identify an analog of mexiletine with superior drug-like properties. Compared to racemic mexiletine, medicinal chemistry optimization of substituted racemic pyridyl phenyl mexiletine analogs resulted in a more potent sodium channel inhibitor with greater selectivity for the sodium over the potassium channel and for late over peak sodium current.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Síndrome do QT Longo
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Miócitos Cardíacos
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Células-Tronco Pluripotentes Induzidas
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Canal de Sódio Disparado por Voltagem NAV1.5
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Doença do Sistema de Condução Cardíaco
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Mexiletina
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article