Discovery of fluorobenzimidazole HCV NS5A inhibitors. Issue 22 (15th November 2016)

• Record Type: Journal Article
• Authors: Randolph, John T.; Flentge, Charles A.; Donner, Pamela; Rockway, Todd W.; Patel, Sachin V.; Nelson, Lissa; Hutchinson, Douglas K.; Mondal, Rubina; Mistry, Neeta; Reisch, Thomas; Dekhtyar, Tatyana; Krishnan, Preethi; Pilot-Matias, Tami; Stolarik, Deanne F.; Beno, David W.A.; Wagner, Rolf; Maring, Clarence; Kati, Warren M.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 22(2016)
• Page Start: 5462
• Page End: 5467
• Publication Date: 2016-11-15
• Subjects: HCV -- NS5A inhibitor -- Antiviral; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.10.030
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Research toward a next-generation HCV NS5A inhibitor has identified fluorobenzimidazole analogs that demonstrate potent, broad-genotype in vitro activity against HCV genotypes 1–6 replicons as well as HCV NS5A variants that are orders of magnitude less susceptible to inhibition by first-generation NS5A inhibitors in comparison to wild-type replicons. The fluorobenzimidazole inhibitors have improved pharmacokinetic properties in comparison to non-fluorinated benzimidazole analogs. Discovery of these inhibitors was facilitated by exploring SAR in a structurally simplified inhibitor series.