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

ABSTRACT: 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??M). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties.

SUBMITTER: Yoon JH

PROVIDER: S-EPMC7126094 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Yoon Ji Hye JH Lee Jun Young JY Lee Jihye J Shin Young Sup YS Jeon Sangeun S Kim Dong Eon DE Min Jung Sun JS Song Jong Hwan JH Kim Seungtaek S Kwon Sunoh S Jin Young-Hee YH Jang Min Seong MS Kim Hyoung Rae HR Park Chul Min CM

Bioorganic & medicinal chemistry letters 20191009 23

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 (IC<sub>50</sub> = 86 nM) and low toxicity (CC<sub>50</sub> > 25 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties. ...[more]

PMID: 31624041

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