鲁扎司韦（MK-8408）的发现：一种强效的泛基因型丙型肝炎病毒NS5A抑制剂，对常见耐药相关多态性具有优化活性。
Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms.
作者信息
Tong Ling, Yu Wensheng, Chen Lei, Selyutin Oleg, Dwyer Michael P, Nair Anilkumar G, Mazzola Robert, Kim Jae-Hun, Sha Deyou, Yin Jingjun, Ruck Rebecca T, Davies Ian W, Hu Bin, Zhong Bin, Hao Jinglai, Ji Tao, Zan Shuai, Liu Rong, Agrawal Sony, Xia Ellen, Curry Stephanie, McMonagle Patricia, Bystol Karin, Lahser Frederick, Carr Donna, Rokosz Laura, Ingravallo Paul, Chen Shiying, Feng Kung-I, Cartwright Mark, Asante-Appiah Ernest, Kozlowski Joseph A
机构信息
Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China.
出版信息
J Med Chem. 2017 Jan 12;60(1):290-306. doi: 10.1021/acs.jmedchem.6b01310. Epub 2016 Nov 15.
We describe the research that led to the discovery of compound 40 (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 40 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.
我们描述了导致发现化合物40（鲁扎斯韦，MK-8408）的研究过程，它是一种泛基因型丙型肝炎病毒非结构蛋白5A（NS5A）抑制剂，具有“扁平”的GT1突变体谱。这种NS5A抑制剂含有独特的四环吲哚核心，同时保留了我们之前的NS5A抑制剂的咪唑-脯氨酸-缬氨酸Moc基序。化合物40目前正处于早期临床试验阶段，作为一种全口服直接抗病毒药物（DAA）方案的一部分，正在接受评估，用于治疗慢性丙型肝炎病毒感染。
Zotero 插件