Discovery of Indole- and Indazole-acylsulfonamides as Potent and Selective Na_V1.7 Inhibitors for the Treatment of Pain

Abstract

3-Aryl-indole and 3-aryl-indazole derivatives were identified as potent and selective Na_v1.7 inhibitors. Compound 29 was shown to be efficacious in the mouse formalin assay and also reduced complete Freund's adjuvant (CFA)-induced thermal hyperalgesia and chronic constriction injury (CCI) induced cold allodynia and 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 ganglion exposure and Na_V1.7 potency associated with 29.