Discovery of morpholine-based aryl sulfonamides as Nav1.7 inhibitors. Issue 5 (1st March 2018)

• Record Type: Journal Article
• Authors: Wu, Yong-Jin; Guernon, Jason; McClure, Andrea; Venables, Brian; Rajamani, Ramkumar; Robbins, Kevin J.; Knox, Ronald J.; Matchett, Michele; Pieschl, Rick L.; Herrington, James; Bristow, Linda J.; Meanwell, Nicholas A.; Olson, Richard; Thompson, Lorin A.; Dzierba, Carolyn
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 5(2018)
• Page Start: 958
• Page End: 962
• Publication Date: 2018-03-01
• Subjects: Nav1.7 inhibitor -- Aryl sulfonamides -- Morpholine-based -- Pain; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.035
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Replacement of the piperidine ring in the lead benzenesulfonamide Nav 1.7 inhibitor1 with a weakly basic morpholine core resulted in a significant reduction in Nav 1.7 inhibitory activity, but the activity was restored by shortening the linkage from methyleneoxy to oxygen. These efforts led to a series of morpholine-based aryl sulfonamides as isoform-selective Nav 1.7 inhibitors. This report describes the synthesis and SAR of these analogs.