Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742

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• 作者：Wensheng Yu^a ; ^{wensheng.yu@merck.com" class="auth_mail" title="E-mail the corresponding author} ; Craig A. Coburn^b ; Anilkumar G. Nair^a ; Michael Wong^a ; Ling Tong^a ; Michael P. Dwyer^a ; Bin Hu^c ; Bin Zhong^c ; Jinglai Hao^c ; De-Yi Yang^a ; Oleg Selyutin^a ; Yueheng Jiang^a ; Stuart B. Rosenblum^a ; Seong Heon Kim^a ; Brian J. Lavey^a ; Guowei Zhou^a ; Razia Rizvi^a ; Bandarpalle B. Shankar^a ; Qingbei Zeng^a ; Lei Chen^a ; Sony Agrawal^d ; Donna Carr^d ; Laura Rokosz^d ; Rong Liu^e ; Stephanie Curry^e ; Patricia McMonagle^e ; Paul Ingravallo^e ; Fred Lahser^e ; Ernest Asante-Appiah^e ; Amin Nomeir^f ; Joseph A. Kozlowski^a
• 关键词：BVAZQCUMNICBAQ-PZHYSIFUSA-N ; CGWIQTMOZACRHO-JGWWVUOKSA-N ; PLGAPCRWWULNNY-QIKRQHTMSA-N ; HVQPLOYCSSNTLU-ZLRJGBHPSA-N ; XSZNVZHMIMRTSW-AVNCCPHYSA-N ; KSSPCKOUBGFLGY-AVNCCPHYSA-N ; ZTKDISPEEJLVLZ-DYSJQOLXSA-N ; ZHDQPFPOWUOIDN-LEIRQVFBSA-N ; WRCDRUFXYBYOMQ-MOKNKNHJSA-N ; NDPGCXHNKBEWGE-NPTDXBJXSA-N ; OULXSYATJCDLKS-ZLRJGBHPSA-N ; BWIDBJZHNXZZRR-SKFDGZKZSA-N ; QMWHDHATHSZAOV-MDHUNEKDSA-N ; AUOIUPIMBMLOIR-DCTIZDGDSA-N ; NPMMJCGMZQERJW-JYUYELIWSA-N ; PAYKQBIPPSKPSN-LCSZIOFPSA-N ; MCPQISFWVIDUMA-LTDGQNSRSA-N ; LOIPKGB
• 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：3800-3805
• 全文大小：2037 K

文摘

HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein we describe our continued research efforts around the alkyl “Z group” modification of the tetracyclic indole-based NS5A inhibitor MK-8742, which led to the discovery of a series of potent NS5A inhibitors. Compounds 10 and 19 are of particular interests since they are as potent as our previous leads and have much improved rat pharmacokinetic profiles.