| Literature DB >> 29681153 |
Wensheng Yu, Ling Tong, Oleg Selyutin, Lei Chen, Bin Hu1, Bin Zhong1, Jinglai Hao1, Tao Ji1, Shuai Zan1, Jingjun Yin, Rebecca T Ruck, Stephanie Curry, Patricia McMonagle, Sony Agrawal, Laura Rokosz, Donna Carr, Paul Ingravallo, Karin Bystol, Frederick Lahser, Rong Liu, Shiying Chen, Kung-I Feng, Mark Cartwright, Ernest Asante-Appiah, Joseph A Kozlowski.
Abstract
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.Entities:
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Year: 2018 PMID： 29681153 DOI： 10.1021/acs.jmedchem.7b01927
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446