methyl 2-(1-isopropyl-1H-indol-3-yl)-2-oxoacetate | 1318754-45-8

• 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-(1-isopropyl-1H-indol-3-yl)-2-oxoacetate
• 英文别名: Methyl 2-oxo-2-(1-propan-2-ylindol-3-yl)acetate
• CAS: 1318754-45-8
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: NMKMTIMSUGTHSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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-(1-isopropyl-1H-indol-3-yl)-2-oxoacetate 在 potassium tert-butylate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  基于（氮杂）吲哚基马来酰亚胺的糖原合酶激酶3β共价抑制剂的设计与合成

  摘要：

  作为多种信号转导途径中的重要激酶，GSK-3β已成为化学探针发现和药物开发的有吸引力的靶标。与已开发的多种可逆抑制剂相比，GSK-3β的共价抑制剂明显缺乏。在这里，我们报告了通过优化非共价相互作用和反应性基团的一系列共价GSK-3β抑制剂的发现。在这些共价抑制剂中，具有轻度α-氟甲基酰胺反应性基团的化合物38b出现为针对GSK-3β的选择性共价抑制剂，可有效抑制糖原合酶和tau蛋白的磷酸化，并增加活细胞中β-catenin的水平。此外，化合物38b具有高渗透性，不是P的底物-糖蛋白。

  DOI：

  10.1039/c8ob00642c
• 作为产物：
  描述：

  吲哚-3-乙醛酰氯 在 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 8.0h， 生成 methyl 2-(1-isopropyl-1H-indol-3-yl)-2-oxoacetate
  参考文献：
  名称：

  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

  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.

  DOI：

  10.1016/j.bmc.2014.12.026

文献信息

• 3-(1,2,4-三氮唑并[4,3-a]吡啶-3-基)-4- (1H-吲哚-3-基)马来酰亚胺类衍生物及其 制备方法和应用
  申请人：浙江工业大学

  公开号：CN104693198B

  公开（公告）日：2017-03-08

  本发明提供一类具有新型结构的3‑(1,2,4‑三氮唑并[4,3‑a]吡啶‑3‑基)‑4‑(1H‑吲哚‑3‑基)马来酰亚胺类衍生物及其制备方法和应用，该类化合物可用于治疗缺血性脑中风。化合物结构通式如下：。
• 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.
• Structure–Activity Relationship and Pharmacokinetic Studies of Sotrastaurin (AEB071), a Promising Novel Medicine for Prevention of Graft Rejection and Treatment of Psoriasis
  作者：Jürgen Wagner、Peter von Matt、Bernard Faller、Nigel G. Cooke、Rainer Albert、Richard Sedrani、Hansjörg Wiegand、Christian Jean、Christian Beerli、Gisbert Weckbecker、Jean-Pierre Evenou、Gerhard Zenke、Sylvain Cottens

  DOI：10.1021/jm200469u

  日期：2011.9.8

  Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure - activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.