2-chloro-1-(5-hydroxy-1H-indol-3-yl)ethanone | 1531588-03-0

• 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: 2-chloro-1-(5-hydroxy-1H-indol-3-yl)ethanone
• 英文别名: 2-chloro-1-(5-hydroxy-1H-indol-3-yl)ethan-1-one
• CAS: 1531588-03-0
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: XICXLNAQUBBDNZ-UHFFFAOYSA-N

物化性质

• 沸点：
  454.2±30.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-苯基-4-羟基哌啶 、 2-chloro-1-(5-hydroxy-1H-indol-3-yl)ethanone 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以30%的产率得到1-(5-hydroxy-1H-indol-3-yl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone
  参考文献：
  名称：

  From NMDA receptor antagonists to discovery of selective σ2 receptor ligands

  摘要：

  Following previous studies focused on the search for new molecules targeting GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl) ethanone derivatives has been synthesized by using Microwave Assisted Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target effects we also tested their affinity towards sigma receptors. Binding assay revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl) ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a and 6a were efficient and selective ligands toward sigma 2 receptor (K-i values of 10 nM and 20 nM, respectively). Thus, in this case the discovery of new sigma 2 receptor selective ligands was an unexpected result emerging from the screening of cross-activity against other CNS receptors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.014
• 作为产物：
  描述：

  2-氯-1-(5-甲氧基-1H-吲哚-3-基)-乙酮 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以81%的产率得到2-chloro-1-(5-hydroxy-1H-indol-3-yl)ethanone
  参考文献：
  名称：

  From NMDA receptor antagonists to discovery of selective σ2 receptor ligands

  摘要：

  Following previous studies focused on the search for new molecules targeting GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl) ethanone derivatives has been synthesized by using Microwave Assisted Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target effects we also tested their affinity towards sigma receptors. Binding assay revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl) ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a and 6a were efficient and selective ligands toward sigma 2 receptor (K-i values of 10 nM and 20 nM, respectively). Thus, in this case the discovery of new sigma 2 receptor selective ligands was an unexpected result emerging from the screening of cross-activity against other CNS receptors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.014

文献信息

• Structure-guided design of new indoles as negative allosteric modulators (NAMs) of N-methyl-d-aspartate receptor (NMDAR) containing GluN2B subunit
  作者：Maria Rosa Buemi、Laura De Luca、Stefania Ferro、Emilio Russo、Giovambattista De Sarro、Rosaria Gitto

  DOI：10.1016/j.bmc.2016.02.021

  日期：2016.4

  Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50 = 47 nM) and 3 (IC50 = 25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data. (C) 2016 Elsevier Ltd. All rights reserved.