Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease

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• 作者：Xianfeng Li ; Yong-Kang Zhang ; Yang Liu ; Suoming Zhang ; Charles Z. Ding ; Yasheen Zhou ; Jacob J. Plattner ; Stephen J. Baker ; Liang Liu ; Wei Bu ; Wieslaw M. Kazmierski ; Lois L. Wright ; Gary K. Smith ; Rich
• 关键词：Hepatitis C virus ; HCV NS3 ; Protease inhibitor ; Macrocyclic inhibitor ; Benzoxaborole
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 December 2010
• 年：2010
• 卷：20
• 期：24
• 页码：7493-7497
• 全文大小：667 K

文摘

HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1′ region was synthesized and evaluated. The resulting P1–P3 and P2–P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described.