3-Oxoisoindoline-1-carboxamides: potent, state-dependent blockers of voltage-gated sodium channel NaV1. 7 with efficacy in rat pain models

…, E Venyike, S Oerther, K Hygge Blakeman…

Index: MacSari, Istvan; Besidski, Yevgeni; Csjernyik, Gabor; Nilsson, Linda I.; Sandberg, Lars; Yngve, Ulrika; Ahlin, Kristofer; Bueters, Tjerk; Eriksson, Anders B.; Lund, Per-Eric; Venyike, Elisabet; Oerther, Sandra; Hygge Blakeman, Karin; Luo, Lei; Arvidsson, Per I. Journal of Medicinal Chemistry, 2012 , vol. 55, # 15 p. 6866 - 6880

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Citation Number: 16

Abstract

The voltage-gated sodium channel NaV1. 7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure–activity relationships, and in vitro and in vivo characterization of a novel series of NaV1. 7 inhibitors based on the oxoisoindoline core. ...