The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics

Abstract

In this article, we describe the discovery of an aryl ether series of potent and selective Na_v1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Na_v channels, we propose this series binds in the same location. We describe the development of this series from a published starting point, highlighting key selectivity and potency data, and several studies designed to validate Na_v1.3 as a target for pain.