Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10596811 | Bioorganic & Medicinal Chemistry Letters | 2010 | 6 Pages |
Abstract
Conformational modeling has been successfully applied to the design of cyclic bioisosteres used to replace a conformationally rigid amide bond in a series of thiophene carboxylate inhibitors of HCV NS5B polymerase. Select compounds were equipotent with the original amide series. Single-point mutant binding studies, in combination with inhibition structure-activity relationships, suggest this new series interacts at the Thumb-II domain of NS5B. Inhibitor binding at the Thumb-II site was ultimately confirmed by solving a crystal structure of 8b complexed with NS5B.
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Authors
Hanbiao Yang, Robert T. Hendricks, Nidhi Arora, Dov Nitzan, Calvin Yee, Matthew C. Lucas, Yanli Yang, Amy Fung, Sonal Rajyaguru, Seth F. Harris, Vincent J.P. Leveque, Julie Q. Hang, Sophie Le Pogam, Deborah Reuter, Gisele A. Tavares,