Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives as potential MERS-CoV inhibitors

[摘要] 3-Acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives were synthesized and evaluated to show high anti-MERS-CoV inhibitory activities. Among them, 6,8-difluoro-3-isobutyryl-2-((2,3,4-trifluorophenyl)amino)quinolin-4(1H)-one (6u) exhibits high inhibitory effect (IC50 = 86 nM) and low toxicity (CC50 > 25 mu M). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties.

[发布日期] 2019-12-01

[关键词] MERS-CoV;RNA virus;3-Acyl-2-amino-1,4-dihydroquinolin-4(1H)-ones;Inhibitor;SAR optimization