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ID: ALA4330091

Journal: Bioorg Med Chem

Title: The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain.

Authors: Brown AD, Bagal SK, Blackwell P, Blakemore DC, Brown B, Bungay PJ, Corless M, Crawforth J, Fengas D, Fenwick DR, Gray V, Kemp M, Klute W, Malet Sanz L, Miller D, Murata Y, Payne CE, Skerratt S, Stevens EB, Warmus JS.

Abstract: The voltage gated sodium channel NaV1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole NaV1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.

CiteXplore: 30538065

DOI: 10.1016/j.bmc.2018.12.002