RECENT ADVANCES IN METAL-CATALYZED C-H FUNCTIONALIZATION OF PYRIMIDINONES, QUINAZOLINONES AND FUSED QUINAZOLINONES

International audienceThis review emphasises the recent developments in metal-catalyzed functionalization using direct C-H bond activation of pyrimidinones (uracils), quinazolinones and quinazolinone-based fused poly-N-heterocycles as well as metal-catalyzed C-H functionalization of high valuable 2-arylquinazolinones

Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases

International audienceA library of thirty novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives belonging to four series designated as 12, 13, 14 and 15 was efficiently prepared, helped by microwave-assisted technology when required. The efficient multistep synthesis of methyl 6-amino-2-cyano- benzo[d]thiazole-7-carboxylate (1) has been reinvestigated and performed on a multigram scale. The inhibitory potency of the final products against five kinases involved in Alzheimer’s disease was evaluated. This study demonstrates that some molecules of the 12 and 13 series described in this paper are particularly promising for the development of new multi-target inhibitors of kinase

Synthesis of bioactive 2-(arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff reaction or Cu- catalyzed intramolecular C-S bond formation

International audienceA library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient multistep synthesis of the key 6-amino-3-cyclopropylquinazolin-4(3H)-one (3) has been reinvestigated and performed on a multigram scale from the starting 5-nitroanthranilic acid. The inhibitory potency of the final products was evaluated against five kinases involved in Alzheimer’s disease and showed that some molecules of the 17 series described in this paper are particularly promising for the development of novel multi-target inhibitors of kinases

Three catalysts for activating carbon-hydrogen bonds

International audienceTransition metal–catalyzed arylation of C–H bonds has been intensively studied for forming C–C bonds in complex-molecule synthesis (1). An acidic C–H bond (for example, one near a double bond or an O atom) is cleaved to form a carbon–metal bond, which then couples to arene. Many of these organometallic species can be generated catalytically. Much less research has dealt with unreactive nonacidic sp3 C–H bond functionalization (3). On page 1304 of this issue, Shaw et al. (3) report an efficient and general method that focuses on arylation of sp3 C–H bonds at carbon atoms adjacent to amines and to cyclic ethers by combining nickel, visible-light photoredox, and hydrogen-atom transfer (HAT) catalysis

Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-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-f]quinazolin-9(8H)-one (also called FC162) 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. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610)

Late-Stage C-H Arylation of Bioactive Heterocycles for the Synthesis of Promising Kinases Inhibitors

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Late-Stage C-H Arylation of Bioactive Heterocycles for the Synthesis of Promising Kinases Inhibitors

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Late-Stage C-H arylation of Thiazolo[5,4-f]quinazolin-9(8H)-one Backbone: Synthesis of an Array of Potential Kinase Inhibitors

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Late-Stage C-H arylation of Thiazolo[5,4-f]quinazolin-9(8H)-one Backbone: Synthesis of an Array of Potential Kinase Inhibitors

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Copper-mediated C-H Activation of quinazolinones and thiazoloquinazolinones for the Synthesis of kinase Inhibitors

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