Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3 Inhibitors and Anti-Ischemic Agents

doi:10.1111/cbdd.12546

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	Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3 Inhibitors and Anti-Ischemic Agents
	Ye, Qing 1,2; Li, Qiu 2; Zhou, Yubo1 ; Xu, Lei 1; Mao, Weili 2; Gao, Yuanxue 3; Li, Chenhui 3; Xu, Yuan 3; Xu, Yazhou 3; Liao, Hong 3
刊名	CHEMICAL BIOLOGY & DRUG DESIGN
	2015-10
卷号	86 期号:4 页码:746-752
关键词	anti-ischemic agents GSK-3 inhibitors kinase activity maleimides
ISSN号	1747-0277
DOI	10.1111/cbdd.12546
文献子类	Article
英文摘要	A series of novel 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides were designed, synthesized, and biologically evaluated for their GSK-3 inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3 protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3 substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3 activity. In the invitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen-glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the invivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK-3 inhibitors with potential neuroprotective activity against brain ischemic stroke.
资助项目	Natural Science Foundation of Zhejiang[LY14H300003] ; Postdoctoral Science Foundation of China[2014M550256] ; State Key Laboratory of Drug Research[SIMM1403KF-02] ; Fundamental Research Funds for the Central Universities[JKZD2013006] ; National Natural Science Foundation of China[21402241] ; Natural Science Foundation of Jiangsu Province[BK20130653]
WOS关键词	GLYCOGEN-SYNTHASE KINASE-3-BETA ; FOCAL CEREBRAL-ISCHEMIA ; VALPROIC ACID ; PHOSPHORYLATION ; EXCITOTOXICITY ; NEURONS ; LITHIUM ; MODELS ; STROKE ; POTENT
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000362163500039
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276389]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物安全性评价中心
通讯作者	Gao, Jianrong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Zhejiang Univ Technol, State Key Lab Breeding Base Green Chem Synth Tech, Hangzhou 310032, Zhejiang, Peoples R China; 3.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Ye, Qing,Li, Qiu,Zhou, Yubo,et al. Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3 Inhibitors and Anti-Ischemic Agents[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2015,86(4):746-752.
APA	Ye, Qing.,Li, Qiu.,Zhou, Yubo.,Xu, Lei.,Mao, Weili.,...&Pang, Tao.(2015).Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3 Inhibitors and Anti-Ischemic Agents.CHEMICAL BIOLOGY & DRUG DESIGN,86(4),746-752.
MLA	Ye, Qing,et al."Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3 Inhibitors and Anti-Ischemic Agents".CHEMICAL BIOLOGY & DRUG DESIGN 86.4(2015):746-752.