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

ABSTRACT: Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-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(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-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.

SUBMITTER: Lee JY

PROVIDER: S-EPMC7920804 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Lee Jun Young JY Shin Young Sup YS Jeon Sangeun S Lee Se In SI Noh Soojin S Cho Jung-Eun JE Jang Min Seong MS Kim Seungtaek S Song Jong Hwan JH Kim Hyoung Rae HR Park Chul Min CM

Bioorganic & medicinal chemistry letters 20210302

Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-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(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC<sub>50</sub> ...[more]

PMID: 33662537

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