Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3β (GSK-3β) inhibitors
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- 作者：Qing Ye ; Guiqing Xu ; Dan Lv ; Zhe Cheng ; Jia Li ; Yongzhou Hu
- 关键词：4-Azaindolyl-indolyl-maleimides ; Synthesis ; Biological evaluation ; GSK-3β ; inhibitors
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2009
- 出版时间：1 July 2009
- 年：2009
- 卷：17
- 期：13
- 页码：4302-4312
- 全文大小：541 K
文摘
A series of novel 4-azaindolyl-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high potency to GSK-3β. Among them, compound 7c was the most promising GSK-3β inhibitor. Preliminary structure–activity relationships were discussed based on the experimental data obtained and showed that different substituents on the indole ring and side chains at 1-position of indole had varying degrees of influence on the GSK-3β inhibitory potency. In a cell-based functional assay, compounds 7c and 15a significantly reduced Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β.