|
|||||
|
|
HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic glycinamide cap derivatives |
|
| Authors: | 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 Jin-Hua Sun Mengping Liu Robert A Fridell Julie A Lemm Min Gao Jay O Knipe Nicholas A Meanwell Lawrence B Snyder |
| Institution: | 1. Department of Medicinal Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA;2. Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA;3. Department of Computer-Aided Drug Design, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA;4. Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA |
| Abstract: | 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. |
| Keywords: | Daclatasvir HCV NS5A Mandelamide X-ray Pan-genotype HCV replicon inhibition Phenylglycine |
| 本文献已被 ScienceDirect 等数据库收录！ | |