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

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

  • Bioorg Med Chem Lett. 2019 Dec 1;29(23):126727. doi: 10.1016/j.bmcl.2019.126727.
Ji Hye Yoon 1,  Jun Young Lee 1,  Jihye Lee 2,  Young Sup Shin 1,  Sangeun Jeon 2,  Dong Eon Kim 3,  Jung Sun Min 3,  Jong Hwan Song 1,  Seungtaek Kim 4,  Sunoh Kwon 3,  Young-Hee Jin 3,  Min Seong Jang 5,  Hyoung Rae Kim 1,  Chul Min Park 1
Affiliations

Affiliations

  • 1 Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea.
  • 2 Respiratory Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea.
  • 3 Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
  • 4 Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea.
  • 5 Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea.
PMID: 31624041 DOI: 10.1016/j.bmcl.2019.126727
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 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties.

Keywords

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

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