3-[1-(4-fluorophenyl)-1H-indol-3-yl]propyl-1-methanesulfonate | 1027544-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-[1-(4-fluorophenyl)-1H-indol-3-yl]propyl-1-methanesulfonate
• 英文别名: 3-[1-(4-Fluorophenyl)indol-3-yl]propyl methanesulfonate
• CAS: 1027544-26-8
• 化学式: C₁₈H₁₈FNO₃S
• 分子量: 347.41
• InChiKey: KFSKNLONFCYPMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  56.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基-2-溴苄胺 、 3-[1-(4-fluorophenyl)-1H-indol-3-yl]propyl-1-methanesulfonate 在 potassium carbonate 作用下， 以 various solvent(s) 为溶剂， 反应 16.0h， 以46%的产率得到N-[(2-bromophenyl)methyl]-3-[1-(4-fluorophenyl)indol-3-yl]-N-methylpropan-1-amine
  参考文献：
  名称：

  Substituted benzylaminoalkylindoles with preference for the σ2 binding site

  摘要：

  In the attempt to develop new sigma ligands we synthesized a series of N-benzyl-3-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the phenyl ring. The displacement percentages of [H-3]-DTG and [H-3]-(+)-pentazocine determined in rat liver homogenates by these compounds at the fixed 100 nM concentration have been determined as a preliminary evaluation of their sigma(1) and sigma(2) affinity, respectively.The results suggested that the phenyl substituents may positively modulate, in comparison with the unsubstituted compound, the ability to displace [H-3]-DTG from sigma(2) sites, whereas the same phenyl substituents reduced the displacement percentages of [H-3]-(+)-pentazocine from sigma(1), sites. Some of these compounds were selected for radioligand binding assays. Compounds with a butylene intermediate chain displayed the greatest binding affinity for sigma(2) over sigma(1) receptors. The butylene derivative with 2,4-dimethyl substitution on the phenyl ring showed the greatest sigma(2) affinity (sigma K-2(i) = 5.9 nM) and an appreciable sigma(2) over sigma(1) selectivity (sigma K-1(i)/sigma K-2(i) = 22). The obtained results suggest that a butylene chain separating the indole moiety from variously substituted benzylamino groups may be required to their interaction with a hypothetical secondary sigma(2) binding site. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.09.012
• 作为产物：
  描述：

  吲哚-3-丙醇 在 N-甲基吡咯烷酮 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 、 zinc(II) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 3-[1-(4-fluorophenyl)-1H-indol-3-yl]propyl-1-methanesulfonate
  参考文献：
  名称：

  具有亚纳摩尔亲和力且对sigma 2结合位点优先的Sigma配体。1. 3-（ω-氨基烷基）-1H-吲哚。

  摘要：

  合成了一系列的4-（1H-吲哚-3-基）-1-丁基取代的4-苯基哌啶，4-苯基-1,2,3,6-四氢吡啶和4-苯基哌嗪。苯基任选地被4-氟或2-甲氧基取代基取代。用这些化合物实现了对sigma 1和sigma 2结合位点的高亲和力。另外，这些化合物对5-羟色胺5-HT1A和5-HT2A，多巴胺D2和肾上腺素α1受体具有较高的亲和力。在吲哚氮原子处引入4-氟苯基取代基使得对σ2结合位点具有亚纳摩尔亲和力的非常选择性的σ2配体。这种化合物的原型是1-（4-氟苯基）-3- [4- [4-（4-氟苯基）-1-哌啶基] -1-丁基] -1H-吲哚，11a（代码Lu 29） -253）。该化合物具有以下结合亲和力：IC50（sigma 1）= 16 nM，IC50（sigma 2）= 0.27 nM，IC50（5-HT1A）= 22,000 nM，IC50（5-HT2A）= 270 nM，IC50（D2）=

  DOI：

  10.1021/jm00011a019

文献信息

• .sigma. Ligands with Subnanomolar Affinity and Preference for the .sigma.2 Binding Site. 1. 3-(.omega.-Aminoalkyl)-1H-indoles
  作者：Jens Perregaard、Ejner K. Moltzen、Eddi Meier、Connie Sanchez

  DOI：10.1021/jm00011a019

  日期：1995.5

  2-methoxy substituents. High affinity for both sigma 1 and sigma 2 binding sites was achieved with these compounds. Additionally, these compounds had relatively high affinity for serotonin 5-HT1A and 5-HT2A, dopamine D2, and adrenergic alpha 1 receptors. Introduction of a 4-fluorophenyl substituent at the indole nitrogen atom rendered very selective sigma 2 ligands with subnanomolar affinity for the sigma 2

  合成了一系列的4-（1H-吲哚-3-基）-1-丁基取代的4-苯基哌啶，4-苯基-1,2,3,6-四氢吡啶和4-苯基哌嗪。苯基任选地被4-氟或2-甲氧基取代基取代。用这些化合物实现了对sigma 1和sigma 2结合位点的高亲和力。另外，这些化合物对5-羟色胺5-HT1A和5-HT2A，多巴胺D2和肾上腺素α1受体具有较高的亲和力。在吲哚氮原子处引入4-氟苯基取代基使得对σ2结合位点具有亚纳摩尔亲和力的非常选择性的σ2配体。这种化合物的原型是1-（4-氟苯基）-3- [4- [4-（4-氟苯基）-1-哌啶基] -1-丁基] -1H-吲哚，11a（代码Lu 29） -253）。该化合物具有以下结合亲和力：IC50（sigma 1）= 16 nM，IC50（sigma 2）= 0.27 nM，IC50（5-HT1A）= 22,000 nM，IC50（5-HT2A）= 270 nM，IC50（D2）=
• Substituted benzylaminoalkylindoles with preference for the σ2 binding site
  作者：Maria Grazia Mamolo、Daniele Zampieri、Caterina Zanette、Chiara Florio、Simona Collina、Mariangela Urbano、Ornella Azzolina、Luciano Vio

  DOI：10.1016/j.ejmech.2007.09.012

  日期：2008.10

  In the attempt to develop new sigma ligands we synthesized a series of N-benzyl-3-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the phenyl ring. The displacement percentages of [H-3]-DTG and [H-3]-(+)-pentazocine determined in rat liver homogenates by these compounds at the fixed 100 nM concentration have been determined as a preliminary evaluation of their sigma(1) and sigma(2) affinity, respectively.The results suggested that the phenyl substituents may positively modulate, in comparison with the unsubstituted compound, the ability to displace [H-3]-DTG from sigma(2) sites, whereas the same phenyl substituents reduced the displacement percentages of [H-3]-(+)-pentazocine from sigma(1), sites. Some of these compounds were selected for radioligand binding assays. Compounds with a butylene intermediate chain displayed the greatest binding affinity for sigma(2) over sigma(1) receptors. The butylene derivative with 2,4-dimethyl substitution on the phenyl ring showed the greatest sigma(2) affinity (sigma K-2(i) = 5.9 nM) and an appreciable sigma(2) over sigma(1) selectivity (sigma K-1(i)/sigma K-2(i) = 22). The obtained results suggest that a butylene chain separating the indole moiety from variously substituted benzylamino groups may be required to their interaction with a hypothetical secondary sigma(2) binding site. (C) 2007 Elsevier Masson SAS. All rights reserved.