Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 1;27(1):230-239.
doi: 10.1016/j.bmc.2018.12.002. Epub 2018 Dec 4.

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

Alan D Brown  1 , Sharan K Bagal  1 , Paul Blackwell  2 , David C Blakemore  3 , Bruce Brown  2 , Peter J Bungay  4 , Martin Corless  2 , James Crawforth  2 , David Fengas  5 , David R Fenwick  2 , Victoria Gray  2 , Mark Kemp  2 , Wolfgang Klute  2 , Laia Malet Sanz  2 , Duncan Miller  2 , Yoshihisa Murata  2 , C Elizabeth Payne  4 , Sarah Skerratt  1 , Edward B Stevens  4 , Joseph S Warmus  6
Affiliations

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

Alan D Brown et al. Bioorg Med Chem. .

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.

Keywords: Benzimidazole; Inflammatory pain; Na(V)1.8; Neuropathic pain; PF-06305591; SCN10A; Voltage gated sodium channel.

PubMed Disclaimer

MeSH terms

Substances

LinkOut - more resources