Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®

Autor:	Cheng Y. Yang, Cottell Jeromy J, Krygowski Evan S, Jason K. Perry, Katana Ashley Anne, Mei Yu, Yujin Wang, Tran Chinh Viet, Guangyu Zhao, Yang Zheng-Yu, Kelly Wang, Yu-Jen Lee, Ruoyu Gong, Eric M. Gorman, Alejandra Trejo-Martin, Yang Tian, Kato Darryl, Erik Mogalian, Bacon Elizabeth M, Link John O, James G. Taylor, Guofeng Cheng, Zipfel Sheila
Rok vydání:	2019
Předmět:	Macrocyclic Compounds Genotype Sofosbuvir Voxilaprevir Hepatitis C virus Clinical Biochemistry Pharmaceutical Science Hepacivirus Microbial Sensitivity Tests Viral Nonstructural Proteins medicine.disease_cause Antiviral Agents Heterocyclic Compounds 4 or More Rings 01 natural sciences Biochemistry Structure-Activity Relationship Drug Discovery medicine Humans Protease Inhibitors Protease inhibitor (pharmacology) HCV NS5A Inhibitor NS5A Molecular Biology Sulfonamides Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry virus diseases Virology humanities digestive system diseases 0104 chemical sciences Drug Combinations 010404 medicinal & biomolecular chemistry Molecular Medicine Carbamates Velpatasvir Tablets medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 29:2415-2427
ISSN:	0960-894X
Popis:	Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67e1fbe8045531556d55ed210cd6fe2a https://doi.org/10.1016/j.bmcl.2019.04.027 Zobrazit plný text záznamu Full Text from ScienceDirect