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
  • 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.