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 : a Journal of Synthetic Chemistry and Natural Product Chemistry
Florence CoulyThierry Besson

Abstract

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.

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Citations

Sep 1, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dongdong ZhangRui Wang

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Methods Mentioned

BETA
column chromatography

Software Mentioned

Sigma
Plot

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