Synthesis and biological evaluation of 2‐benzylaminoquinazolin ‐4( 3 H )‐one derivatives as a potential treatment for SARS‐CoV ‐2 release_j5xilyl2yfckxojuzzxtflw3ky

by Jun Young Lee, Young Sup Shin, Sangeun Jeon, Se In Lee, Jung‐Eun Cho, Subeen Myung, Min Seong Jang, Seungtaek Kim, Jong Hwan Song, Hyoung Rae Kim, Chul Min Park

Published in Bulletin of the Korean Chemical Society (Print) by Wiley.

2022   Volume 43, Issue 3, p412-416

Abstract

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(3H)-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(3H)-one (Compound 39) showed highest anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration value greater than that of remdesivir (IC50 = 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.
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Type  article-journal
Stage   published
Date   2022-01-23
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DOI  10.1002/bkcs.12470
PubMed  35440837
PMC  PMC9011860
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