| Literature DB >> 25613678 |
Guangming Chen1, Hongyu Ren1, Nanjing Zhang1, William Lennox1, Anthony Turpoff1, Steven Paget1, Chunshi Li1, Neil Almstead1, F George Njoroge2, Zhengxian Gu1, Jason Graci1, Stephen P Jung1, Joseph Colacino1, Fred Lahser2, Xin Zhao1, Marla Weetall1, Amin Nomeir2, Gary M Karp1.
Abstract
A structure-activity relationship investigation of various 6-(azaindol-2-yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the identification of a potent series of 7-azaindoles that target the hepatitis C virus NS4B. Compound 2ac, identified via further optimization of the series, has excellent potency against the HCV 1b replicon with an EC50 of 2nM and a selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also has excellent oral plasma exposure levels in rats, dogs and monkeys and has a favorable liver to plasma distribution profile in rats.Entities:
Keywords: 6-(Azaindol-2-yl)pyridine-3-sulfonamides; HCV inhibitors; NS4B; Replicon; Structure–activity relationship
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Year: 2015 PMID： 25613678 DOI： 10.1016/j.bmcl.2014.12.093
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823