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Synthesis and biological evaluation of 2‐benzylaminoquinazolin ‐4( 3 H )‐one derivatives as a potential treatment for SARS‐CoV ‐2
Author(s) -
Lee Jun Young,
Shin Young Sup,
Jeon Sangeun,
Lee Se In,
Cho JungEun,
Myung Subeen,
Jang Min Seong,
Kim Seungtaek,
Song Jong Hwan,
Kim Hyoung Rae,
Park Chul Min
Publication year - 2022
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.12470
Subject(s) - pharmacokinetics , chemistry , metabolic stability , covid-19 , ic50 , ether , pharmacology , solubility , stereochemistry , biochemistry , in vitro , medicine , disease , organic chemistry , infectious disease (medical specialty)
Despite the continuing global crisis caused by coronavirus disease 2019 (COVID‐19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2‐benzylaminoquinazolin‐4(3 H )‐one derivatives and demonstrated that they are effective against SARS‐CoV‐2. Among the synthesized derivatives, 7‐chloro‐2‐(((4‐chlorophenyl)(phenyl)methyl)amino)quinazolin‐4(3 H )‐one (Compound 39 ) showed highest anti‐SARS‐CoV‐2 activity, with a half‐maximal inhibitory concentration value greater than that of remdesivir (IC 50 = 4.2 μM vs. 7.6 μM, respectively), which gained urgent approval from the U.S. Food and Drug Administration. In addition, Compound 39 showed good results in various assays measuring metabolic stability, human ether a‐go‐go, Cytochromes P450 (CYPs) inhibition, and plasma protein binding (PPB), and showed better solubility and pharmacokinetics than our previous work.