Development of Kinase Inhibitors via Metal-Catalyzed C–H Arylation of 8-Alkyl-thiazolo[5,4-f]-quinazolin-9-ones Designed by Fragment-Growing Studies

Autor:	Florence Couly, Marine Harari, Carole Dubouilh-Benard, Laetitia Bailly, Emilie Petit, Julien Diharce, Pascal Bonnet, Laurent Meijer, Corinne Fruit, Thierry Besson
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	thiazolo[5 4-f]quinazolin-9(8H)-ones microwave-assisted synthesis C–H arylation protein kinases DYRK1A CDK5 GSK-3 CLK1 CK1 Organic chemistry QD241-441
Zdroj:	Molecules, Vol 23, Iss 9, p 2181 (2018)
Druh dokumentu:	article
ISSN:	1420-3049 23092181
DOI:	10.3390/molecules23092181
Popis:	Efficient metal catalyzed C–H arylation of 8-alkyl-thiazolo[5,4-f]-quinazolin-9-ones was explored for SAR studies. Application of this powerful chemical tool at the last stage of the synthesis of kinase inhibitors allowed the synthesis of arrays of molecules inspired by fragment-growing studies generated by molecular modeling calculations. Among the potentially active compounds designed through this strategy, FC162 (4c) exhibits nanomolar IC50 values against some kinases, and is the best candidate for the development as a DYRK kinase inhibitor.
Databáze:	Directory of Open Access Journals
Externí odkaz:	https://doaj.org/article/a5c5ba93d71c4074a8e149ffd8cfd7c3 Zobrazit plný text záznamu View record in DOAJ Plný text ve formátu PDF