HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic glycinamide cap derivatives
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- 作者：Makonen Belema ; Van N. Nguyen ; Denis R. St. Laurent ; Omar D. Lopez ; Yuping Qiu ; Andrew C. Good ; Peter T. Nower ; Lourdes Valera ; Donald R. O¡¯Boyle II ; Jin-Hua Sun ; Mengping Liu ; Robert A. Fridell ; Julie A. Lemm ; Min Gao ; Jay O. Knipe ; Nicholas A. Meanwell ; Lawrence B. Snyder
- 关键词：Daclatasvir ; HCV ; NS5A ; Mandelamide X-ray ; Pan-genotype HCV replicon inhibition ; Phenylglycine
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：1 August, 2013
- 年：2013
- 卷：23
- 期：15
- 页码：4428-4435
- 全文大小：3286 K
文摘
The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds ong class=""boldFont"">2b ong> and ong class=""boldFont"">2c ong> provided the first dual genotype-1a/1b (GT-1a/1b) inhibitor class that demonstrated a significant improvement in potency toward GT-1a replicons compared to that of the initial program lead, stilbene ong class=""boldFont"">2a ong>. Structure-activity relationship (SAR) studies that uncovered an alternate phenylglycine-based cap series that exhibit further improvements in virology profile, along with some insights into the pharmacophoric elements associated with the GT-1a potency, are described.