Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors. Issue 22 (15th November 2015)

• Record Type: Journal Article
• Authors: Suzuki, Sayaka; Kuroda, Takeshi; Kimoto, Hiroko; Domon, Yuki; Kubota, Kazufumi; Kitano, Yutaka; Yokoyama, Tomihisa; Shimizugawa, Akiko; Sugita, Ryusuke; Koishi, Ryuta; Asano, Daigo; Tamaki, Kazuhiko; Shinozuka, Tsuyoshi; Kobayashi, Hiroyuki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 22(2015)
• Page Start: 5419
• Page End: 5423
• Publication Date: 2015-11-15
• Subjects: Voltage-gated sodium channel -- Pain -- CNS side effects -- High-throughput screening -- Piperidine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.09.005
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A novel class of NaV 1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine9o showed potent human and mouse NaV 1.7 inhibitory activities with fair subtype selectivity over NaV 1.5. Compound9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.