Bioorg Med Chem Lett . Design, Synthesis and Biological Evaluation of 2-Aminoquinazolin-4(3H)-one Derivatives as Potential SARS-CoV-2 and MERS-CoV Treatments

[tetano]

Bioorg Med Chem Lett


. 2021 Mar 1;127885.
doi: 10.1016/j.bmcl.2021.127885. Online ahead of print.
Design, Synthesis and Biological Evaluation of 2-Aminoquinazolin-4(3H)-one Derivatives as Potential SARS-CoV-2 and MERS-CoV Treatments


Jun Young Lee ¹ , Young Sup Shin ¹ , Sangeun Jeon ² , Se In Lee ¹ , Soojin Noh ¹ , Jung-Eun Cho ¹ , Min Seong Jang ³ , Seungtaek Kim ² , Jong Hwan Song ¹ , Hyoung Rae Kim ¹ , Chul Min Park ⁴



Affiliations

• PMID: 33662537
• DOI: 10.1016/j.bmcl.2021.127885

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.

Keywords: 2-aminoquinazolinone; MERS-CoV; SARS-CoV-2; antiviral; coronavirus.