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Molecules 2013, 18(5), 5498-5516; https://doi.org/10.3390/molecules18055498

Synthesis and Biological Evaluation of 3-Benzisoxazolyl-4-indolylmaleimides as Potent, Selective Inhibitors of Glycogen Synthase Kinase-3β

1
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China
2
The National Center for Drug Screening, Shanghai 201203, China
3
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
*
Authors to whom correspondence should be addressed.
Received: 21 March 2013 / Revised: 2 May 2013 / Accepted: 7 May 2013 / Published: 13 May 2013
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Abstract

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC50 value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N1-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7jl and 7oq could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay. View Full-Text
Keywords: 3-benzisoxazolyl-4-indolylmaleimides; synthesis; GSK-3β; biological activity; docking; SAR 3-benzisoxazolyl-4-indolylmaleimides; synthesis; GSK-3β; biological activity; docking; SAR
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Ye, Q.; Li, M.; Zhou, Y.; Pang, T.; Xu, L.; Cao, J.; Han, L.; Li, Y.; Wang, W.; Gao, J.; Li, J. Synthesis and Biological Evaluation of 3-Benzisoxazolyl-4-indolylmaleimides as Potent, Selective Inhibitors of Glycogen Synthase Kinase-3β. Molecules 2013, 18, 5498-5516.

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