Discovery of a novel class of isoxazoline voltage gated sodium channel blockers

Analogs of the previously reported voltage gated sodium channel blocker CDA54 were prepared in which one of the amide functions was replaced with aromatic and non-aromatic heterocycles. Replacement of the amide with an aromatic heterocycle resulted in significant loss of sodium channel blocking activity, while non-aromatic heterocycle replacements were well tolerated. (C) 2009 Elsevier Ltd. All rights reserved.