Discovery of MK-6169, a Potent Pan-Genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Substitutions

摘要: We describe the discovery of MK-6169, a potent and pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions. SAR studies around combination changes to both valine aminal carbon region elbasvir led series compounds substantially improved potency substitutions in major genotypes, as well good pharmacokinetics rat dog. Through further optimization key leads from this effort, MK-6169 (21) was discovered preclinical candidate for development.