Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742

详细信息    查看全文

• 作者：Wensheng Yu^a ; ; Craig A. Coburn^b ; Anilkumar G. Nair^a ; Michael Wong^a ; Stuart B. Rosenblum^a ; Guowei Zhou^a ; Michael P. Dwyer^a ; Ling Tong^a ; Bin Hu^c ; Bin Zhong^c ; Jinglai Hao^c ; Tao Ji^c ; Shuai Zan^c ; Seong Heon Kim^a ; Qingbei Zeng^a ; Oleg Selyutin^a ; Lei Chen^a ; Frederic Masse^d ; Sony Agrawal^d ; Rong Liu^e ; Ellen Xia^d ; Ying Zhai^d ; Stephanie Curry^e ; Patricia McMonagle^e ; Paul Ingravallo^e ; Ernest Asante-Appiah^e ; Mingxiang Lin^f ; Joseph A. Kozlowski^a
• 关键词：XXMYVGBAHJZAHH-DBFVGOLASA-N ; FLDBOLOBRLMSHU-LEIRQVFBSA-N ; VLINDSPVYPOCKD-DYSJQOLXSA-N ; GHZSWSOYQIFBAA-HIIDTSOHSA-N ; VLKGLFRTXSAWLC-HIIDTSOHSA-N ; DDWRYTGXAPUCCU-MOKNKNHJSA-N ; IQYCGFUBAXSQGT-MOKNKNHJSA-N ; DVOCGCPQHPYVLQ-MOKNKNHJSA-N ; AYEKKEBXMVMQCW-NPTDXBJXSA-N ; MHRXLNLLUKFSPA-NPTDXBJXSA-N ; SQUFCGHNIRTTQO-VPQGWNJZSA-N ; KNLKVPVXRMGYFZ-VPQGWNJZSA-N ; UJXHOBOEBQXXDO-ZIEJMRAYSA-N ; IROXEJUPIAHIKR-ZIEJMRAYSA-N ; RHXGEOLLIYZLGW-RKUGBEGMSA-N ; IYLNUNSJACDBHO-NZRCMKGGSA-N ; GUDYLVLIGVZFHC-PFHKGJDSSA-N
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：26
• 期：15
• 页码：3414-3420
• 全文大小：2074 K

文摘

Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45–47, 54, 56, and 65, which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition.