Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers

A series of low molecular weight biaryl substituted oxazoles, imidazoles, and thiazoles were identified as Na v1.7 blockers. These state dependent sodium channel blockers were synthesized and evaluated for treatment of neuropathic pain. Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency.