| Literature DB >> 30538065 |
Alan D Brown1, Sharan K Bagal1, Paul Blackwell2, David C Blakemore3, Bruce Brown2, Peter J Bungay4, Martin Corless2, James Crawforth2, David Fengas5, David R Fenwick2, Victoria Gray2, Mark Kemp2, Wolfgang Klute2, Laia Malet Sanz2, Duncan Miller2, Yoshihisa Murata2, C Elizabeth Payne4, Sarah Skerratt1, Edward B Stevens4, Joseph S Warmus6.
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.Entities:
Keywords: Benzimidazole; Inflammatory pain; Na(V)1.8; Neuropathic pain; PF-06305591; SCN10A; Voltage gated sodium channel
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Year: 2018 PMID： 30538065 DOI： 10.1016/j.bmc.2018.12.002
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641