Cardiac Ion Channel Inhibition

التفاصيل البيبلوغرافية
العنوان: Cardiac Ion Channel Inhibition
المؤلفون: Bordoni, Cinzia, Brough, Daniel J., Davison, Gemma, Hunter, James H., Lopez-Fernandez, J. Daniel, McAdam, Kate, Miller, Duncan C., Morese, Pasquale A., Papaioannou, Alexia, Uguen, Mélanie, Ratcliffe, Paul, Sitnikov, Nikolay, Waring, Michael J.
المصدر: The Medicinal Chemist's Guide to Solving ADMET Challenges ; page 403-492 ; ISBN 9781788012270 9781788012270 9781839160493 9781788016414
بيانات النشر: The Royal Society of Chemistry
سنة النشر: 2021
الوصف: Interaction with cardiac ion channels can potentially result in severe or even fatal cardiac side effects. The most prominent of cardiac channels, human ether-a-go-go-related gene (hERG), voltage-gated sodium channel 1.5 (NaV1.5) and voltage-gated calcium channel 1.2 (CaV1.2), which traffic major ion currents shaping cardiac action potential, are recognized as primary counter-screen targets. These channels possess relatively large inner pores with multiple binding sites and can accommodate a variety of structurally diverse ligands. This chapter provides a short overview of in vitro approaches in preclinical cardiotoxicity screening, gives a summary of available structural data and pharmacophore models for hERG, NaV1.5 and CaV1.2 as well as discusses medicinal chemistry strategies that were successfully applied to mitigate cardiotoxicity risk. The major highlighted approaches are lipophilicity reduction, basicity reduction and removal or modification of (hetero)aromatic substituents. The strategies are illustrated by multiple examples from recent literature.
نوع الوثيقة: book part
اللغة: English
ردمك: 978-1-78801-227-0
978-1-78801-641-4
1-78801-227-5
1-78801-641-6
DOI: 10.1039/9781788016414-00403
الاتاحة: http://dx.doi.org/10.1039/9781788016414-00403
https://books.rsc.org/books/edited-volume/chapter-pdf/1587980/bk9781788012270-00403.pdf
رقم الانضمام: edsbas.2E9062D6
قاعدة البيانات: BASE
الوصف
ردمك:9781788012270
9781788016414
1788012275
1788016416
DOI:10.1039/9781788016414-00403