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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

1
Normandie University, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, 76000 Rouen, France
2
Institut de Chimie Organique et Analytique (ICOA), Université d’Orléans, UMR CNRS, 7311 BP 6759, 45067 Orléans CEDEX 2, France
3
ManRos Therapeutics, Perharidy Peninsula, 29680 Roscoff, France
*
Authors to whom correspondence should be addressed.
Molecules 2018, 23(9), 2181; https://doi.org/10.3390/molecules23092181
Received: 9 August 2018 / Revised: 24 August 2018 / Accepted: 27 August 2018 / Published: 29 August 2018
(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)
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. View Full-Text
Keywords: thiazolo[5,4-f]quinazolin-9(8H)-ones; microwave-assisted synthesis; C–H arylation; protein kinases; DYRK1A; CDK5; GSK-3; CLK1; CK1 thiazolo[5,4-f]quinazolin-9(8H)-ones; microwave-assisted synthesis; C–H arylation; protein kinases; DYRK1A; CDK5; GSK-3; CLK1; CK1
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MDPI and ACS Style

Couly, F.; Harari, M.; Dubouilh-Benard, C.; Bailly, L.; Petit, E.; Diharce, J.; Bonnet, P.; Meijer, L.; Fruit, C.; Besson, T. 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. Molecules 2018, 23, 2181.

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