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

Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part I

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Microwave-assisted synthesis of novel N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides inspired by marine topsentines and nortopsentines

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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(8 H)-one Backbone: Synthesis of an Array of Potential Kinase Inhibitors

International audienceDriven by the need of structural modification to establish structure-activity relationships, the regioselective C–H bond activation of thiazolo[5,4-f]quinazolin-9(8H)-one backbone has been developed to furnish the corresponding C2-arylated valuable scaffold. This strategy provides a synthetically streamlined and useful route for late-stage diversification of this attractive skeleton, required in drug discovery. A more eco-friendly synthesis of thiazolo[5,4-f]quinazolin-9(8H)-ones is also described giving access to these aforementioned compounds in a facile manner

Synthesis of Bioactive 2-(arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation

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Synthesis of polyfunctionalized benzo[d]thiazoles as novel anthranilic acid derivatives

International audienceA small library of valuable novel polyfunctionalized benzo[d]thiazole derivatives was prepared in a straightforward and convenient manner. Here again, 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) proved to be an efficient agent for merging a 2-cyanothiazole ring to an arene counterpart

First synthesis of 4-aminopyrido[2′,3′:4,5]furo[3,2-d]pyrimidines

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Monitoring of Catalyst-Free Microwave-Assisted MCR-Type Synthesis of 2-Amino-3-cyano-4H-chromene Derivatives Using Raman Spectrometry

Abstract In order to prepare an array of β-cyanoenamine derivatives as potential precursors of heterocyclic systems with pharmaceutical interest, the synthesis of fifteen polyfunctionalized 4H-chromenes was realized via a microwave-assisted and catalyst-free three-component reaction. Microwave-heated reactions were monitored by Raman spectroscopy, enabling a fast and efficient setting of the process parameters. This study confirms that this monitoring tool may have some limitations linked to homogeneity of reaction medium. This work also investigates the use of some bio-sourced and sustainable solvents currently studied in many works. Ethanol remains the most suitable for this synthesis

Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives

International audienceWe previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1δ/ε, GSK3α/β and DYRK1A). As a result, we have identified promising compounds targeting CK1δ/ε and DYRK1A and displaying micromolar and submicromolar IC50 values