1. Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742
- Author
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Ling Tong, Craig A. Coburn, Michael P. Dwyer, Paul Ingravallo, Stephanie Curry, Mingxiang Lin, Guowei Zhou, Stuart B. Rosenblum, Shuai Zan, Wensheng Yu, Joseph A. Kozlowski, Ying Zhai, Oleg Selyutin, Bin Hu, Michael Wong, Lei Chen, Rong Liu, Ernest Asante-Appiah, Qingbei Zeng, Jinglai Hao, Seong Heon Kim, Anilkumar G. Nair, Ellen Xia, Tao Ji, Patricia McMonagle, Frédéric Massé, Bin Zhong, and Sony Agrawal
- Subjects
Male ,0301 basic medicine ,Elbasvir ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Hepacivirus ,Microbial Sensitivity Tests ,Viral Nonstructural Proteins ,Antiviral Agents ,01 natural sciences ,Biochemistry ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Potency ,Structure–activity relationship ,HCV NS5A Inhibitor ,NS5A ,Molecular Biology ,Benzofurans ,Indole test ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Aryl ,Organic Chemistry ,Imidazoles ,virus diseases ,digestive system diseases ,Rats ,0104 chemical sciences ,030104 developmental biology ,chemistry ,Aminal ,Molecular Medicine - Abstract
Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45-47, 54, 56, and 65, which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition.
- Published
- 2016
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