Discovery of pyrrolo-benzo-1,4-diazines as potent Nav1.7 sodium channel blockers

Abstract A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed potent Na v 1.7 inhibitory activity and moderate selectivity over Na v 1.5. The syntheses, structure–activity relationships, and selected pharmacokinetic data of these analogs are described. Compound 41 displayed anti-nociceptive efficacy in the rat CFA pain model at 100 mpk oral dosing.