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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jun Young, Shin, Young Sup, Jeon, Sangeun, Lee, Se In, Noh, Soojin, Cho, Jung-Eun, Jang, Min Seong, Kim, Seungtaek, Song, Jong Hwan, Kim, Hyoung Rae, Park, Chul Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier Ltd. 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920804/
https://www.ncbi.nlm.nih.gov/pubmed/33662537
http://dx.doi.org/10.1016/j.bmcl.2021.127885
Descripción
Sumario: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(50) < 0.25 μM) and anti-MERS-CoV activities (IC(50) < 1.1 μM) with no cytotoxicity (CC(50) > 25 μM). In addition, both compounds showed acceptable results in metabolic stabilities, hERG binding affinities, CYP inhibitions, and preliminary PK studies.

Ejemplares similares