Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms
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- 作者：Ling TongWensheng Yu ; Lei ChenOleg Selyutin ; Michael P. Dwyer ; Anilkumar G. Nair ; Robert Mazzola ; Jae-Hun Kim ; Deyou Sha ; Jingjun Yin ; Rebecca T. Ruck ; Ian W. Davies ; Bin Hu ; Bin Zhong ; Jinglai Hao ; Tao Ji ; Shuai Zan ; Rong Liu ; Sony Agrawal ; Ellen Xia ; Stephanie Curry ; Patricia McMonagle ; Karin Bystol ; Frederick Lahser ; Donna Carr ; Laura Rokosz ; Paul Ingravallo ; Shiying Chen ; Kung-I Feng ; Mark Cartwright ; Ernest Asante-Appiah ; Joseph A. Kozlowski
- 刊名：Journal of Medicinal Chemistry
- 出版年：2017
- 出版时间：January 12, 2017
- 年：2017
- 卷：60
- 期：1
- 页码：290-306
- 全文大小：937K
- ISSN：1520-4804
文摘
We describe the research that led to the discovery of compound <b>40b> (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a “flat” GT1 mutant profile. This NS5A inhibitor contains a unique tetracyclic indole core while maintaining the imidazole–proline–valine Moc motifs of our previous NS5A inhibitors. Compound <b>40b> is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV infection.