Synthesis and biological evaluation of 3-([1,2,4]triazolo [4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3 beta inhibitors and neuroprotective agents
文献类型：期刊论文
| 作者 | Ye, Qing1,2; Mao, Weili1; Zhou, Yubo2 ; Xu, Lei2; Li, Qiu1; Gao, Yuanxue3; Wang, Jing3; Li, Chenhui3; Xu, Yazhou3; Xu, Yuan3
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2015-03-01 |
| 卷号 | 23期号:5页码:1179-1188 |
| 关键词 | GSK-3 beta inhibitors Maleimides Kinase activity Neuroprotective agents |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2014.12.026 |
| 文献子类 | Article |
| 英文摘要 | A series of novel 3-([1,2,4] triazolo[4,3-a] pyridin-3-yl)-4-(indol-3-yl)-maleimides were designed, prepared and evaluated for their GSK-3 beta inhibitory activities. Most compounds showed high potency to GSK-3 beta inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3 beta substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3 beta. In the in vitro neuronal injury models, compounds 7c, 7f, 7h, 7l and 7m prevented neuronal death against glutamate, oxygen-glucose deprivation and nutrient serum deprivation which are associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 7f reduced infarct size by 15% and improved the neurological deficit following focal cerebral ischemia. These findings may provide new insights into the development of novel GSK-3b inhibitors with potential neuroprotective activity. (C) 2015 Published by Elsevier Ltd. |
| WOS关键词 | GLYCOGEN-SYNTHASE KINASE-3-BETA ; FOCAL CEREBRAL-ISCHEMIA ; ALZHEIMERS-DISEASE ; VALPROIC ACID ; PHOSPHORYLATION ; TAU ; EXCITOTOXICITY ; LOCALIZATION ; EXPRESSION ; NEURONS |
| 资助项目 | Fundamental Research Funds for the Central Universities, China[JKZD2013006] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000349966700026 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276628]  |
| 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.Zhejiang Univ Technol, State Key Lab Breeding Base Green Chem Synth Tech, Hangzhou 310032, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, 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,Mao, Weili,Zhou, Yubo,et al. Synthesis and biological evaluation of 3-([1,2,4]triazolo [4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3 beta inhibitors and neuroprotective agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2015,23(5):1179-1188. |
| APA | Ye, Qing.,Mao, Weili.,Zhou, Yubo.,Xu, Lei.,Li, Qiu.,...&Pang, Tao.(2015).Synthesis and biological evaluation of 3-([1,2,4]triazolo [4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3 beta inhibitors and neuroprotective agents.BIOORGANIC & MEDICINAL CHEMISTRY,23(5),1179-1188. |
| MLA | Ye, Qing,et al."Synthesis and biological evaluation of 3-([1,2,4]triazolo [4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3 beta inhibitors and neuroprotective agents".BIOORGANIC & MEDICINAL CHEMISTRY 23.5(2015):1179-1188. |
入库方式： OAI收割
来源：上海药物研究所
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