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

• Published in: Bioorganic & medicinal chemistry letters 2019-12, Vol.29 (23), p.126727-126727, Article 126727
• Main Authors: Yoon, Ji Hye, Lee, Jun Young, Lee, Jihye, Shin, Young Sup, Jeon, Sangeun, Kim, Dong Eon, Min, Jung Sun, Song, Jong Hwan, Kim, Seungtaek, Kwon, Sunoh, Jin, Young-hee, Jang, Min Seong, Kim, Hyoung Rae, Park, Chul Min
• Format: Article
• Language: English
• Subjects: 3-Acyl-2-amino-1,4-dihydroquinolin-4(1H)-ones; Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Cell Survival - drug effects; Chlorocebus aethiops; CHO Cells; Cricetulus; Dose-Response Relationship, Drug; Humans; Inhibitor; MERS-CoV; Mice; Microbial Sensitivity Tests; Middle East Respiratory Syndrome Coronavirus - drug effects; Molecular Structure; NIH 3T3 Cells; Quinolones - chemical synthesis; Quinolones - chemistry; Quinolones - pharmacology; RNA virus; SAR optimization; Structure-Activity Relationship; Vero Cells
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.126727

[Display omitted] 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 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties.