Discovery of fluorobenzimidazole HCV NS5A inhibitors
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- 作者：John T. Randolph ; Charles A. Flentge ; Pamela Donner ; Todd W. Rockway ; Sachin V. Patel ; Lissa Nelson ; Douglas K. Hutchinson ; Rubina Mondal ; Neeta Mistry ; Thomas Reisch ; Tatyana Dekhtyar ; Preethi Krishnan ; Tami Pilot-Matias ; Deanne F. Stolarik ; David W.A. Beno ; Rolf Wagner ; Clarence Maring ; Warren M. Kati
- 关键词：HCV ; NS5A inhibitor ; Antiviral
- 刊名：Bioorganic & Medicinal Chemistry Letters
- 出版年：2016
- 出版时间：15 November 2016
- 年：2016
- 卷：26
- 期：22
- 页码：5462-5467
- 全文大小：2549 K
文摘
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.