We previously reported the discovery of diphenylimidazoles as potent sodium channel
blockers, potentially useful in the treatment of epilepsy. In this work we further explore the structural
requirements necessary for the potency of these derivatives with the aim to understand which structural
modifications of the original scaffold could be tolerated in order to retain activity. We have synthesized
new compounds working on the 2-position of the imidazole ring. First we have introduced a
carbonyl spacer, that was subsequently reduced to alcohol. Both carbonyl and alcohol derivatives
have been tested for their ability to block NaV1.6 sodium channel subtype in vitro and for their antiepileptic
activity in rodent acute seizures models.
Keywords: Sodium channels, patch clamp electrophysiology, NaV1.6, Phenyl-imidazoles.
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