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Design, synthesis and biological evaluation of 2-aminoquinazolin-4(3 H )-one derivatives as potential SARS-CoV-2 and MERS-CoV treatments

Authors
  • Lee, Jun Young1
  • Shin, Young Sup1
  • Jeon, Sangeun2
  • Lee, Se In1
  • Noh, Soojin1
  • Cho, Jung-Eun1
  • Jang, Min Seong3
  • Kim, Seungtaek2
  • Song, Jong Hwan1
  • Kim, Hyoung Rae1
  • Park, Chul Min1, 4
  • 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 Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, South Korea
  • 3 Department of Non-Clinical Studies, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, South Korea
  • 4 Korea University of Science and Technology, Daejeon 34114, South Korea
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Mar 02, 2021
Volume
39
Pages
127885–127885
Identifiers
DOI: 10.1016/j.bmcl.2021.127885
PMID: 33662537
PMCID: PMC7920804
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

Abstract

Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3 H )-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3 H )-one ( 9g ) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3 H )-one ( 11e ) showed the most potent anti-SARS-CoV-2 activities (IC50 < 0.25 μM) and anti-MERS-CoV activities (IC50 < 1.1 μM) with no cytotoxicity (CC50 > 25 μM). In addition, both compounds showed acceptable results in metabolic stabilities, hERG binding affinities, CYP inhibitions, and preliminary PK studies.

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