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

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

  • J Med Chem. 2019 Jan 24;62(2):831-856. doi: 10.1021/acs.jmedchem.8b01550.
Guanglin Luo 1,  Ling Chen 1,  Amy Easton 1,  Amy Newton 1,  Clotilde Bourin 1,  Eric Shields 1,  Kathy Mosure 1,  Matthew G Soars 1,  Ronald J Knox 1,  Michele Matchett 1,  Rick L Pieschl 1,  Debra J Post-Munson 1,  Shuya Wang 1,  James Herrington 1,  John Graef 1,  Kimberly Newberry 1,  Digavalli V Sivarao 1,  Arun Senapati 1,  Linda J Bristow 1,  Nicholas A Meanwell 1,  Lorin A Thompson 1,  Carolyn Dzierba 1
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Research and Development , PO Box 4000, Princeton , New Jersey 08543-4000 , United States.
PMID: 30576602 DOI: 10.1021/acs.jmedchem.8b01550
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.

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