methyl 2-(5-chloro-1-methyl-1H-indol-3-yl)-2-oxoacetate | 436161-22-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 2-(5-chloro-1-methyl-1H-indol-3-yl)-2-oxoacetate
• 英文别名: Methyl 2-(5-chloro-1-methylindol-3-yl)-2-oxoacetate
• CAS: 436161-22-7
• 化学式: C₁₂H₁₀ClNO₃
• 分子量: 251.669
• InChiKey: UWZCUFAGWRZGAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-(5-chloro-1-methyl-1H-indol-3-yl)-2-oxoacetate 在 sodium tetrahydroborate 、 氯化铵 作用下， 以 甲醇 、 水 为溶剂， 反应 1.75h， 生成
  参考文献：
  名称：

  手性布朗斯台德酸催化的品哪醇重排

  摘要：

  非对称频哪醇重排：频哪醇重排长期以来已知难以在区域选择性和立体选择性方面进行控制。已经发现，吲哚二醇可以用手性磷酸处理以高效地进行区域和对映选择性的频哪醇重排（参见方案； Ar ＝ 1-萘基）。

  DOI：

  10.1002/anie.201004778
• 作为产物：
  描述：

  2-(5-chloro-1H-indol-3-yl)-2-oxoacetyl chloride 在 sodium hydride 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.5h， 生成 methyl 2-(5-chloro-1-methyl-1H-indol-3-yl)-2-oxoacetate
  参考文献：
  名称：

  用于正电子发射断层显像的基于[18F]马来酰亚胺的糖原合酶激酶3β配体的开发。

  摘要：

  糖原合酶激酶3β（GSK-3β）的失调与神经退行性和精神病性疾病的发病机制有关。因此，开发用于正电子发射断层摄影（PET）成像的GSK-3β放射性示踪剂至关重要，因为这种无创成像技术可以更好地了解GSK-3β活性与活生物体中枢神经系统疾病之间的联系，从而可以及早发现该酶的异常活性。在此，我们报告了一系列高亲和力GSK-3β抑制剂氟取代的马来酰亚胺衍生物的合成和生物学评估。实现了潜在的GSK-3β示踪剂[18F] 10a的放射性合成。在啮齿动物中进行的体内PET初步成像研究显示，大脑摄取中等，尽管在大脑中未观察到饱和结合。有必要进一步完善铅支架，以开发用于中枢神经系统PET成像的[18F]标记的GSK-3放射性示踪剂。

  DOI：

  10.1021/acsmedchemlett.6b00405

文献信息

• [EN] [18F]MALEIMIDE-BASED GLYCOGEN SYNTHASE KINASE-3BETA LIGANDS FOR POSITRON EMISSION TOMOGRAPHY IMAGING AND RADIOSYNTHESIS METHOD<br/>[FR] LIGANDS DE GLYCOGÈNE SYNTHASE KINASE-3β À BASE DE [18F]MALÉIMIDE POUR IMAGERIE PAR TOMOGRAPHIE PAR ÉMISSION DE POSITRONS ET PROCÉDÉ DE RADIOSYNTHÈSE
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2018132636A1

  公开（公告）日：2018-07-19

  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.

  本发明提供了一种具有结构的化合物：（式I），以及一种抑制糖原合成酶激酶-3β（GSK-3β）的方法，包括向受试者施用所述化合物，从而抑制受试者中的GSK-3β。
• 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
  作者：Qing Ye、Weili Mao、Yubo Zhou、Lei Xu、Qiu Li、Yuanxue Gao、Jing Wang、Chenhui Li、Yazhou Xu、Yuan Xu、Hong Liao、Luyong Zhang、Jianrong Gao、Jia Li、Tao Pang

  DOI：10.1016/j.bmc.2014.12.026

  日期：2015.3

  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.
• Synthesis and Evaluation of 3-(furo[2,3<i>-b</i>]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3<i>β</i>Inhibitors and Anti-Ischemic Agents
  作者：Qing Ye、Qiu Li、Yubo Zhou、Lei Xu、Weili Mao、Yuanxue Gao、Chenhui Li、Yuan Xu、Yazhou Xu、Hong Liao、Luyong Zhang、Jianrong Gao、Jia Li、Tao Pang

  DOI：10.1111/cbdd.12546

  日期：2015.10

  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.
• WO2007/8514
  申请人：——

  公开号：——

  公开（公告）日：——
• SUBSTITUTED INDAZOLYL(INDOLYL)MALEIMIDE DERIVATIVES AS KINASE INHIBITORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP1654255B1

  公开（公告）日：2008-08-27