tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Young Sup Shin[SUP] 1 [/SUP], Sangeun Jeon[SUP] 2 [/SUP], Se In Lee[SUP] 1 [/SUP], Soojin Noh[SUP] 1 [/SUP], Jung-Eun Cho[SUP] 1 [/SUP], Min Seong Jang[SUP] 3 [/SUP], Seungtaek Kim[SUP] 2 [/SUP], Jong Hwan Song[SUP] 1 [/SUP], Hyoung Rae Kim[SUP] 1 [/SUP], Chul Min Park[SUP] 4 [/SUP]
Affiliations
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 (IC[SUB]50[/SUB] < 0.25 μM) and anti-MERS-CoV activities (IC[SUB]50[/SUB] < 1.1 μM) with no cytotoxicity (CC[SUB]50[/SUB] > 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.
. 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[SUP] 1 [/SUP], Young Sup Shin[SUP] 1 [/SUP], Sangeun Jeon[SUP] 2 [/SUP], Se In Lee[SUP] 1 [/SUP], Soojin Noh[SUP] 1 [/SUP], Jung-Eun Cho[SUP] 1 [/SUP], Min Seong Jang[SUP] 3 [/SUP], Seungtaek Kim[SUP] 2 [/SUP], Jong Hwan Song[SUP] 1 [/SUP], Hyoung Rae Kim[SUP] 1 [/SUP], Chul Min Park[SUP] 4 [/SUP]
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 (IC[SUB]50[/SUB] < 0.25 μM) and anti-MERS-CoV activities (IC[SUB]50[/SUB] < 1.1 μM) with no cytotoxicity (CC[SUB]50[/SUB] > 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.