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Etude de la fonctionnalisation de thiazolo[5,4-f]quinazolin-9(8H)-ones via des sel de diaryliodonium et synthèse de nouvelles thiazolo[4,5-g]quinazolin-8(7H)-ones, potentiels inhibiteurs de kinases.

Abstract : The synthesis of aromatic polyheterocyclic structures is studied by our group for more than twenty years. The functional modulation of the scaffolds led to two hits compounds, inhibitors of kinase DYRK1A belonging to the CMGC group. To understand the implication of this kinase in neurodegenerative diseases (e.g. Alzheimer Disease), we envisioned to design the first radiotracer of DYRK1A by radiolabeling the hit compounds developed previously. The first part of this manuscript investigates the cyanation reaction of thiazolo [5,4-f] quinazolin-9 (8H) -ones from diaryliodonium, boronic ester or iodine derivatives. This work reveals the difficulty of synthesizing a heteroaryliodonium salt or a boronic ester from the studied heterocycles. Cyanation from a non-toxic cyanide ion source by palladium or copper catalyzed cross-coupling reaction was also unsuccessful. A second part is focus on a new eco-friendly method for the modulation of heterocycles developed by the laboratory with diaryliodonium salts as arylating agents of heteroaromatic rings. This new methodology was successfully applied to original heterocycles including a fused pyrimidinone. A third chapter described new access to linear thiazolo [4,5-g] quinazolin-8 (7H) -ones, functionalized at the C7 position. The thiazole ring fused to a quinazoline was successfully realized by cyclizing of a novel N-arylcyanothioformamides. During this work around 60 novel products were synthesized and characterized.
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Submitted on : Friday, May 13, 2022 - 1:01:12 AM
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Alexandra Pacheco-Benichou. Etude de la fonctionnalisation de thiazolo[5,4-f]quinazolin-9(8H)-ones via des sel de diaryliodonium et synthèse de nouvelles thiazolo[4,5-g]quinazolin-8(7H)-ones, potentiels inhibiteurs de kinases.. Chimie organique. Normandie Université, 2021. Français. ⟨NNT : 2021NORMR055⟩. ⟨tel-03666952⟩

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