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

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 the combination
of changes to both the valine and aminal carbon region of elbasvir
led to the discovery of a series of compounds with substantially improved
potency against common resistance-associated substitutions in the
major genotypes, as well as good pharmacokinetics in both rat and
dog. Through further optimization of key leads from this effort, MK-6169
(21) was discovered as a preclinical candidate for further
development.