N-Aryl azacycles as novel sodium channel blockers

[Display omitted] We have identified a new series of N-aryl azacycles as sodium channel blockers, which showed good potency on Nav1.7 in FLIPR-based and electrophysiological functional assays. Analogs from this series possessed selectivity over hERG, reasonable oral exposure in rat PK studies and ar...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 25; no. 1; pp. 48 - 52
Main Authors:	Lynch, Stephen M., Tafesse, Laykea, Carlin, Kevin, Ghatak, Parijat, Shao, Bin, Abdelhamid, Haissam, Kyle, Donald J.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-01-2015
Subjects:	Amino Acid Sequence Animals Azacycle Cell Membrane Permeability - drug effects Cell Membrane Permeability - physiology Dogs Madin Darby Canine Kidney Cells Molecular Sequence Data Nav1.7 NAV1.7 Voltage-Gated Sodium Channel - physiology Neuropathic pain Rats Sodium channel Sodium Channel Blockers - chemical synthesis Sodium Channel Blockers - pharmacology Nav1.7 Sodium channel Azacycle GAFPQLZAICTDSD-MZGUNHGESA-N ARXQEUXKXBDCRA-JJRNEHELSA-N XJOGDSABVMVHKS-UHFFFAOYSA-N Neuropathic pain Na(v)1.7
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Summary:	[Display omitted] We have identified a new series of N-aryl azacycles as sodium channel blockers, which showed good potency on Nav1.7 in FLIPR-based and electrophysiological functional assays. Analogs from this series possessed selectivity over hERG, reasonable oral exposure in rat PK studies and are predicted to have limited CNS penetration.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2014.11.023