Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742

Autor:	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, Sony Agrawal
Rok vydání:	2016
Předmět:	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
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 26:3414-3420
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f844a35f493581f923c107e7306f3e35 https://doi.org/10.1016/j.bmcl.2016.06.056 Zobrazit plný text záznamu Full Text from ScienceDirect