Department of Medicinal Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4428-35. doi: 10.1016/j.bmcl.2013.05.040. Epub 2013 May 23.
The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds 2b and 2c 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 2a. 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.
异喹啉酰胺系列 HCV NS5A 抑制剂以化合物 2b 和 2c 为代表，提供了首个双基因型 1a/1b（GT-1a/1b）抑制剂类别，与最初的先导化合物二苯乙烯 2a 相比，对 GT-1a 复制子的效力有显著提高。描述了构效关系 (SAR) 研究，揭示了一种替代的基于苯甘氨酸的帽系列，该系列在病毒学特征方面进一步改善，同时对与 GT-1a 效力相关的药效团元素有了一些了解。
