HCV NS5A Replication Complex Inhibitors. Part 4.1 Optimization for Genotype 1a Replicon Inhibitory Activity
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- 作者：Denis R. St. Laurent ; Michael H. Serrano-Wu ; Makonen Belema ; Min Ding ; Hua Fang ; Min Gao ; Jason T. Goodrich ; Rudolph G. Krause ; Julie A. Lemm ; Mengping Liu ; Omar D. Lopez ; Van N. Nguyen ; Peter T. Nower ; Donald R. O鈥橞oyle II ; Bradley C. Pearce ; Jeffrey L. Romine ; Lourdes Valera ; Jin-Hua Sun ; Ying-Kai Wang ; Fukang Yang ; Xuejie Yang ; Nicholas A. Meanwell ; Lawrence B. Snyder
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：March 13, 2014
- 年：2014
- 卷：57
- 期：5
- 页码：1976-1994
- 全文大小：634K
- 年卷期：v.57,no.5(March 13, 2014)
- ISSN：1520-4804
文摘
A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.