Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-]quinazolin-9(8)-one, a Promising Inhibitor of DYRK1A.

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-]quinazolin-9(8)-one (also called ) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells.

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

Efficient metal catalyzed C⁻H arylation of 8-alkyl-thiazolo[5,4-]-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, () exhibits nanomolar IC values against some kinases, and is the best candidate for the development as a DYRK kinase inhibitor.

Pd-Catalyzed and Copper Assisted Regioselective Sequential C2 and C7 Arylation of Thiazolo[5,4-f]quinazolin-9(8H)-one with Aryl Halides.

A selective functionalization of thiazolo[5,4-f]quinazolin-9(8H)-one has been developed through sequential activation of C-H bonds to furnish diarylated compounds. This strategy allows the regioselective C2 and C7 arylation by a judicious choice of coupling partners and bases, requiring no additional ligands or directing groups. Differently substituted N(8)-benzylated-2,7-diaryl-thiazoloquinazolin-9(8H)-ones were thereby obtained in a facile manner.