Discovery of Indole- and Indazole-acylsulfonamides as Potent and Selective NaV1.7 Inhibitors for the Treatment of Pain.
Basic Information
ID: ALA4371076
Journal: J Med Chem
Title: Discovery of Indole- and Indazole-acylsulfonamides as Potent and Selective NaV1.7 Inhibitors for the Treatment of Pain.
Authors: Luo G, Chen L, Easton A, Newton A, Bourin C, Shields E, Mosure K, Soars MG, Knox RJ, Matchett M, Pieschl RL, Post-Munson DJ, Wang S, Herrington J, Graef J, Newberry K, Sivarao DV, Senapati A, Bristow LJ, Meanwell NA, Thompson LA, Dzierba C.
Abstract: 3-Aryl-indole and 3-aryl-indazole derivatives 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 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 NaV1.7 potency associated with 29.
CiteXplore: 30576602
DOI: 10.1021/acs.jmedchem.8b01550
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