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

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 gene...

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Detalles Bibliográficos
Autores principales: Couly, Florence, Harari, Marine, Dubouilh-Benard, Carole, Bailly, Laetitia, Petit, Emilie, Diharce, Julien, Bonnet, Pascal, Meijer, Laurent, Fruit, Corinne, Besson, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225322/
https://www.ncbi.nlm.nih.gov/pubmed/30158487
http://dx.doi.org/10.3390/molecules23092181
Descripción
Sumario: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 IC(50) values against some kinases, and is the best candidate for the development as a DYRK kinase inhibitor.

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