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
文献类型：期刊论文
| 作者 | Ye, Qing1,2; Li, Qiu2; Zhou, Yubo1 ; Xu, Lei1; Mao, Weili2; Gao, Yuanxue3; Li, Chenhui3; Xu, Yuan3; Xu, Yazhou3; Liao, Hong3
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 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. |
| WOS关键词 | GLYCOGEN-SYNTHASE KINASE-3-BETA ; FOCAL CEREBRAL-ISCHEMIA ; VALPROIC ACID ; PHOSPHORYLATION ; EXCITOTOXICITY ; NEURONS ; LITHIUM ; MODELS ; STROKE ; POTENT |
| 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研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000362163500039 |
| 出版者 | WILEY-BLACKWELL |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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