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

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

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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.
Keywords: 3-benzisoxazolyl-4-indolylmaleimides; synthesis; GSK-3β; biological activity; docking; SAR 3-benzisoxazolyl-4-indolylmaleimides; synthesis; GSK-3β; biological activity; docking; SAR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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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