Discovery of Indole- and Indazole-acylsulfonamides as Potent and Selective NaV1.7 Inhibitors for the Treatment of Pain

3-Aryl-indole and 3-aryl- indazolederivatives were identified as potent and selective Nav1.7 inhibitors. Compound 29 was shown to be efficacious in the mouse formalin assay and also reduced complete Freund’s adjuvant(CFA)-induced thermal hyperalgesiaand chronic constriction injury (CCI) induced cold allodyniaand models of inflammatory and neuropathic pain, respectively, following intraperitoneal (IP) doses of 30 mg/kg. The observed efficacy could be correlated with the mouse dorsal root ganglionexposure and NaV1.7 potency associated with 29.