Discovery and initial optimization of alkoxyanthranilic acid derivatives as inhibitors of HCV NS5B polymerase. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Parcella, Kyle; Nickel, Andrew; Beno, Brett R.; Sheriff, Steven; Wan, Changhong; Wang, Ying-Kai; Roberts, Susan B.; Meanwell, Nicholas A.; Kadow, John F.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 2(2017)
• Page Start: 295
• Page End: 298
• Publication Date: 2017-01-15
• Subjects: Hepatitis C virus (HCV) -- NS5B polymerase -- Allosteric inhibitors -- Primer grip; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.11.054
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Alkoxyanthranilic acid derivatives have been identified to inhibit HCV NS5B polymerase, binding in an allosteric site located at the convergence of the palm and thumb regions. Information from co-crystal structures guided the structural design strategy. Ultimately, two independent structural modifications led to a similar shift in binding mode that when combined led to a synergistic improvement in potency and the identification of inhibitors with sub-micromolar HCV NS5B binding potency.