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Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core

[Image: see text] Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series...

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Detalles Bibliográficos
Autores principales: Dvorakova, Marcela, Langhansova, Lenka, Temml, Veronika, Pavicic, Antonio, Vanek, Tomas, Landa, Premysl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040043/
https://www.ncbi.nlm.nih.gov/pubmed/33854702
http://dx.doi.org/10.1021/acsmedchemlett.1c00004
Descripción
Sumario:[Image: see text] Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series of quinazoline derivatives were prepared and tested for their potential inhibitory activity toward COX-1 and COX-2. Of the prepared compounds, 11 exhibited interesting COX-1 selectivity, with 8 compounds being totally COX-1-selective. The IC(50) value of the best quinazoline inhibitor was 64 nM. The structural features ensuring COX-1 selectivity were elucidated using in silico modeling.