噻唑并[5,4-f]喹唑啉-9(8H)-酮作为丝氨酸/苏氨酸激酶多靶点导向配体的合成
Synthesis of Thiazolo[5,4-f]quinazolin-9(8H)-ones as Multi-Target Directed Ligands of Ser/Thr Kinases.
作者信息
Hédou Damien, Godeau Julien, Loaëc Nadège, Meijer Laurent, Fruit Corinne, Besson Thierry
机构信息
Normandie Univ; Uni Rouen; INSA; CNRS, COBRA, UMR 6014, 76000 Rouen, France.
Protein Phosphorylation & Human Disease group, Station Biologique, 29680 Roscoff, France.
出版信息
Molecules. 2016 Apr 30;21(5):578. doi: 10.3390/molecules21050578.
Abstract
A 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 kinases.
摘要
借助微波辅助技术（必要时），高效合成了一个包含30种新型噻唑并[5,4-f]喹唑啉-9(8H)-酮衍生物的文库，这些衍生物分属12、13、14和15四个系列。对6-氨基-2-氰基苯并[d]噻唑-7-羧酸甲酯（1）的高效多步合成进行了重新研究，并在数克规模上进行了制备。评估了最终产物对参与阿尔茨海默病的五种激酶的抑制效力。这项研究表明，本文所述的12和13系列中的一些分子在开发新型多靶点激酶抑制剂方面特别有前景。
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