Design, synthesis and biological evaluation of 2-aminoquinazolin-4(3H)-one derivatives as potential SARS-CoV-2 and MERS-CoV treatments.
Bioorg Med Chem Lett
; 39: 127885, 2021 05 01.
Article
in English
| MEDLINE | ID: covidwho-1116317
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Design
/
Quinazolinones
/
Middle East Respiratory Syndrome Coronavirus
/
SARS-CoV-2
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Bioorg Med Chem Lett
Journal subject:
Biochemistry
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
J.bmcl.2021.127885
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