1-(5,6-dimethoxy-1H-indol-3-yl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanone | 1549940-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(5,6-dimethoxy-1H-indol-3-yl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanone
• 英文别名: 1-(5,6-dimethoxy-1H-indol-3-yl)-3-(4-(4-fluorobenzyl)piperidin-1-yl)propan-1-one；1-(5,6-dimethoxy-1H-indol-3-yl)-2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethanone
• CAS: 1549940-52-4
• 化学式: C₂₄H₂₇FN₂O₃
• 分子量: 410.488
• InChiKey: VNFZSWBHQWSTQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5,6-dimethoxy-1H-indol-3-yl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanone 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以65%的产率得到1-(5,6-dihydroxy-1H-indol-3-yl)-2-(4-(4-fluorobenzyl)piperidin-1-yl)ethanone
  参考文献：
  名称：

  Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors

  摘要：

  A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl) ethane-1,2-dione derivatives that have been screened in [H-3]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50 = 5.5 nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50 nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.040
• 作为产物：
  描述：

  5,6-二甲氧基吲哚 在 盐酸 、 三氯氧磷 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.05h， 生成 1-(5,6-dimethoxy-1H-indol-3-yl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanone
  参考文献：
  名称：

  4-（4-氟苄基）哌啶片段的化学探索以开发新型酪氨酸酶抑制剂

  摘要：

  酪氨酸酶通过单酚羟基化为邻二酚而参与黑色素的产生。为了确定防止皮肤色素沉着和黑色素瘤的新疗法，对该酶的作用进行了广泛的研究。在这项工作中，我们最初确定了3-（4-苄基哌啶-1-基）-1-（1 H-吲哚-3-基）丙-1-酮（1a）是有希望的蘑菇酪氨酸酶抑制剂（IC 50  = 252μM）。 ）。然后，进行了几种化学修饰，并合成了与化合物1a相关的新类似物。生化分析表明，所获得的几种化合物被证明是有效的抑制剂，其IC 50值均低于“先导化合物” 1a和参考抑制剂曲酸，作为众所周知的酪氨酸酶抑制剂。通过Lineweaver-Burk图分析的抑制动力学表明，化合物2 ac和10b充当非竞争性抑制剂，而活性最高的抑制剂2d（IC 50  = 7.56μM）是混合型抑制剂。此外，进行了实验和计算结构研究，以阐明衍生物2d的结合模式。

  DOI：

  10.1016/j.ejmech.2016.10.030

文献信息

• Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors
  作者：Rosaria Gitto、Laura De Luca、Stefania Ferro、Emilio Russo、Giovambattista De Sarro、Mariangela Chisari、Lucia Ciranna、Julio Alvarez-Builla、Ramon Alajarin、Maria Rosa Buemi、Alba Chimirri

  DOI：10.1016/j.bmc.2013.12.040

  日期：2014.2

  A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl) ethane-1,2-dione derivatives that have been screened in [H-3]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50 = 5.5 nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50 nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents. (C) 2013 Elsevier Ltd. All rights reserved.
• Chemical exploration of 4-(4-fluorobenzyl)piperidine fragment for the development of new tyrosinase inhibitors
  作者：Stefania Ferro、Laura De Luca、Maria Paola Germanò、Maria Rosa Buemi、Laura Ielo、Giovanna Certo、Margarita Kanteev、Ayelet Fishman、Antonio Rapisarda、Rosaria Gitto

  DOI：10.1016/j.ejmech.2016.10.030

  日期：2017.1

  demonstrated that several obtained compounds proved to be effective inhibitors showing IC50 values lower both than “lead compound” 1a and reference inhibitor kojic acid, as a well-known tyrosinase inhibitor. The inhibition kinetics analyzed by Lineweaver–Burk plots revealed that compounds 2 a-c and 10b act as non-competitive inhibitors while the most active inhibitor 2d (IC50 = 7.56 μM) is a mixed-type

  酪氨酸酶通过单酚羟基化为邻二酚而参与黑色素的产生。为了确定防止皮肤色素沉着和黑色素瘤的新疗法，对该酶的作用进行了广泛的研究。在这项工作中，我们最初确定了3-（4-苄基哌啶-1-基）-1-（1 H-吲哚-3-基）丙-1-酮（1a）是有希望的蘑菇酪氨酸酶抑制剂（IC 50  = 252μM）。 ）。然后，进行了几种化学修饰，并合成了与化合物1a相关的新类似物。生化分析表明，所获得的几种化合物被证明是有效的抑制剂，其IC 50值均低于“先导化合物” 1a和参考抑制剂曲酸，作为众所周知的酪氨酸酶抑制剂。通过Lineweaver-Burk图分析的抑制动力学表明，化合物2 ac和10b充当非竞争性抑制剂，而活性最高的抑制剂2d（IC 50  = 7.56μM）是混合型抑制剂。此外，进行了实验和计算结构研究，以阐明衍生物2d的结合模式。