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

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; in revised form: 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

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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.

AMA 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(5):5498-5516.

Chicago/Turabian Style

Ye, Qing; Li, Meng; Zhou, Yubo; Pang, Tao; Xu, Lei; Cao, Jiayi; Han, Liang; Li, Yujin; Wang, Weisi; Gao, Jianrong; Li, Jia. 2013. "Synthesis and Biological Evaluation of 3-Benzisoxazolyl-4-indolylmaleimides as Potent, Selective Inhibitors of Glycogen Synthase Kinase-3β." Molecules 18, no. 5: 5498-5516.

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