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

0547414 - ÚEB 2022 RIV US eng J - Journal Article
Dvořáková, Marcela - Langhansová, Lenka - Temml, V. - Pavičić, Antonio - Vaněk, Tomáš - Landa, Přemysl
Synthesis, Inhibitory Activity, and in Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core.
ACS Medicinal Chemistry Letters. Roč. 12, č. 4 (2021), s. 610-616. ISSN 1948-5875
R&D Projects: GA MŠMT(CZ) LTC17048
Institutional support: RVO:61389030
Keywords : Cyclooxygenase * docking * inhibitor * quinazoline * selectivity
OECD category: Organic chemistry
Impact factor: 4.632, year: 2021
Method of publishing: Open access
http://doi.org/10.1021/acsmedchemlett.1c00004

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 IC50 value of the best quinazoline inhibitor was 64 nM. The structural features ensuring COX-1 selectivity were elucidated using in silico modeling.
Permanent Link: http://hdl.handle.net/11104/0323654