163160-55-2Relevant academic research and scientific papers
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-3β inhibitors and neuroprotective agents
Ye, Qing,Mao, Weili,Zhou, Yubo,Xu, Lei,Li, Qiu,Gao, Yuanxue,Wang, Jing,Li, Chenhui,Xu, Yazhou,Xu, Yuan,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
, p. 1179 - 1188 (2015)
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-3β inhibitory activities. Most compounds showed high potency to GSK-3β inhibition with high selectivity. Among them, compounds 7c, 7f, 7h, 7l and 7m significantly reduced GSK-3β substrate Tau phosphorylation at Ser396 in primary neurons, showing the inhibition of cellular GSK-3β. 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-3β inhibitors with potential neuroprotective activity.
3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
Hu, Yuanyuan,Gao, Anhui,Liao, Honghui,Zhang, Mengmeng,Xu, Gaoya,Gao, Lixin,Xu, Lei,Zhou, Yubo,Gao, Jianrong,Ye, Qing,Li, Jia
, (2018/09/06)
A series of 3-(7-azainodyl)-4-indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild-type IDH1. Evaluation of the biological activities at the cellular level showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Preliminary structure–activity relationship (SAR) and molecular modeling studies were discussed based on the experimental data obtained. These findings may provide new insights into the development of novel IDH1/R132H inhibitors.
[18F]MALEIMIDE-BASED GLYCOGEN SYNTHASE KINASE-3BETA LIGANDS FOR POSITRON EMISSION TOMOGRAPHY IMAGING AND RADIOSYNTHESIS METHOD
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Page/Page column 40; 41, (2018/08/03)
The present invention provides a compound having the structure: (Formula I), and a method of inhibiting Glycogen synthase kinase-3 β (GSK-3β) in a subject comprising administering to the subject said compound, so as to thereby inhibit the GSK-3β in the subject.
3 - (1, 2, 4 - triazole [4, 3 - a] pyridine - 3 - yl) - 4 - (1H - Indol - 3 - yl) maleimide derivatives and its preparation method and application
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Paragraph 0035; 0036; 0043; 0044, (2017/08/25)
The invention provides a 3-(1,2,4-triazolo(4,3-a)pyridine-3-yl)-4-(1H-indole-3-yl)maleimide derivative with a novel structure and a preparation method and application of the derivative. The compound can be used for treating ischemic cerebral apoplexy. The general structural formula of the compound is shown in the specification.
Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
, p. 287 - 292 (2017/03/17)
Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3β Inhibitors and Anti-Ischemic Agents
Ye, Qing,Li, Qiu,Zhou, Yubo,Xu, Lei,Mao, Weili,Gao, Yuanxue,Li, Chenhui,Xu, Yuan,Xu, Yazhou,Liao, Hong,Zhang, Luyong,Gao, Jianrong,Li, Jia,Pang, Tao
, p. 746 - 752 (2015/03/30)
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-3β inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3β protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3β substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3β activity. In the in vitro 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 in vivo 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-3β inhibitors with potential neuroprotective activity against brain ischemic stroke.
Discovery of ecopladib, an indole inhibitor of cytosolic phospholipase A2α
Lee, Katherine L.,Foley, Megan A.,Chen, Lihren,Behnke, Mark L.,Lovering, Frank E.,Kirincich, Steven J.,Wang, Weiheng,Shim, Jaechul,Tam, Steve,Shen, Marina W. H.,Khor, SooPeang,Xu, Xin,Goodwin, Debra G.,Ramarao, Manjunath K.,Nickerson-Nutter, Cheryl,Donahue, Frances,Ku, M. Sherry,Clark, James D.,McKew, John C.
, p. 1380 - 1400 (2008/02/01)
The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2α (cPLA 2α, type IVA phospholipase) are described. Inhibitors of cPLA2α are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a submicromolar inhibitor of cPLA2α in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.
N-(indol-3-ylglyoxylyl)amino acid ester derivatives. Synthesis and interaction properties at the benzodiazepine receptor
Primofiore,Da Settimo,Marini,La Motta,Martini,Senatore,Lucacchini
, p. 5 - 12 (2007/10/02)
Several N-(indol-3-ylglyoxylyl)alanine and glycine ester derivatives were prepared to evaluate the influence of the ester group size both on affinity and on activity at the benzodiazepine receptor. Moreover, indol-3-ylglyoxylic acid esters, closely related to 3-alkoxy-β-carbolines, were synthesized and tested in vitro on the benzodiazepine receptor.
