1432914-11-8Relevant articles and documents
Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models
Focken, Thilo,Liu, Shifeng,Chahal, Navjot,Dauphinais, Maxim,Grimwood, Michael E.,Chowdhury, Sultan,Hemeon, Ivan,Bichler, Paul,Bogucki, David,Waldbrook, Matthew,Bankar, Girish,Sojo, Luis E.,Young, Clint,Lin, Sophia,Shuart, Noah,Kwan, Rainbow,Pang, Jodie,Chang, Jae H.,Safina, Brian S.,Sutherlin, Daniel P.,Johnson,Dehnhardt, Christoph M.,Mansour, Tarek S.,Oballa, Renata M.,Cohen, Charles J.,Robinette, C. Lee
supporting information, p. 277 - 282 (2016/03/22)
We report on a novel series of aryl sulfonamides that act as nanomolar potent, isoform-selective inhibitors of the human sodium channel hNaV1.7. The optimization of these inhibitors is described. We aimed to improve potency against hNaV1.7 while minimizing off-target safety concerns and generated compound 3. This agent displayed significant analgesic effects in rodent models of acute and inflammatory pain and demonstrated that binding to the voltage sensor domain 4 site of NaV1.7 leads to an analgesic effect in vivo. Our findings corroborate the importance of hNaV1.7 as a drug target for the treatment of pain.
