2-(4-fluorophenyl)-6-methyl-1H-indole | 911051-47-3

• 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-(4-fluorophenyl)-6-methyl-1H-indole
• CAS: 911051-47-3
• 化学式: C₁₅H₁₂FN
• 分子量: 225.265
• InChiKey: QUAKPGASXNRBEL-UHFFFAOYSA-N

物化性质

• 沸点：
  394.3±27.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  15.8
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-6-methyl-1H-indole 、 N-chloroacetyl thiomorpholine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以28%的产率得到2-[2-(4-Fluorophenyl)-6-methylindol-1-yl]-1-thiomorpholin-4-ylethanone
  参考文献：
  名称：

  Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABAA agonists

  摘要：

  Among the known non-benzodiazepine hypnotic drugs, Zolpidem (1 a), Indiplon (2a) and Zaleplon (2b) have shown high affinity and selectivity for the a, subunit of the GABA-A receptor. Our group has performed pharmacophoric and ADMET-prediction studies to evaluate a virtual library of new molecules based on privileged structures. Among these, we have synthesized a library of N-substituted indoles and a library of N-substituted benzimidazoles. Afterwards, in vitro screening and in vivo spontaneous motor activity in mice has revealed molecules with good in vitro affinities for the a, receptor and potent in vivo induction of sedation. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.031
• 作为产物：
  描述：

  N-[1-(4-fluorophenyl)ethylideneamino]-3-methylaniline 在 zinc(II) chloride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 生成 2-(4-fluorophenyl)-6-methyl-1H-indole
  参考文献：
  名称：

  Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABAA agonists

  摘要：

  Among the known non-benzodiazepine hypnotic drugs, Zolpidem (1 a), Indiplon (2a) and Zaleplon (2b) have shown high affinity and selectivity for the a, subunit of the GABA-A receptor. Our group has performed pharmacophoric and ADMET-prediction studies to evaluate a virtual library of new molecules based on privileged structures. Among these, we have synthesized a library of N-substituted indoles and a library of N-substituted benzimidazoles. Afterwards, in vitro screening and in vivo spontaneous motor activity in mice has revealed molecules with good in vitro affinities for the a, receptor and potent in vivo induction of sedation. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.031

文献信息

• The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB₁ Receptor Positive Allosteric Modulators
  作者：Chih-Chung Tseng、Gemma Baillie、Giulia Donvito、Mohammed A. Mustafa、Sophie E. Juola、Chiara Zanato、Chiara Massarenti、Sergio Dall’Angelo、William T. A. Harrison、Aron H. Lichtman、Ruth A. Ross、Matteo Zanda、Iain R. Greig

  DOI：10.1021/acs.jmedchem.9b00252

  日期：2019.5.23

  (e.g., ZCZ011) featured a 3-nitroalkyl-2-phenyl-indole structure. Although a small number of drugs include the nitro group, it is generally not regarded as being "drug-like", and this is particularly true for aliphatic nitro groups. There are very few case studies where an appropriate bioisostere replaced a nitro group that had a direct role in binding. This may be indicative of the difficulty of replicating

  第一代CB1阳性变构调节剂（例如ZCZ011）具有3-硝基烷基-2-苯基-吲哚结构。尽管少数药物包含硝基，但通常不认为它是“类药物”，对于脂肪族硝基尤其如此。在很少的案例研究中，适当的生物甾体替代了在结合中具有直接作用的硝基。这可能表明复制其结合相互作用的困难。在本文中，我们报道了针对CB1大麻素受体的变构结合位点的配体的设计和合成，其中CF3基团成功取代了脂肪族NO2。通常，带有 的化合物比它们的 当量更有效，并且还显示出改善的体外代谢稳定性。选择性能最佳平衡的 类似物（1）进行进一步的药理评估。体内试验研究表明（±）-1具有与（±）-ZCZ011相似的活性，两者在神经性疼痛的小鼠模型中均显示出有希望的功效。
• AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2421825A1

  公开（公告）日：2012-02-29
• CANNABINOID TYPE 1 RECEPTOR MODULATORS
  申请人：The Governing Council of the University of Toronto

  公开号：US20180118681A1

  公开（公告）日：2018-05-03

  The present disclosure relates to indole derivatives of the formula (I) which are cannabinoid type 1 receptor modulators and which are useful in the treatment of diseases in which modulation of the receptor is beneficial; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.
• [EN] AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS<br/>[FR] AZÉTIDINYL DIAMIDES EN TANT QU'INHIBITEURS DE LA MONOACYLGLYCÉROL LIPASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010124108A1

  公开（公告）日：2010-10-28

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Y, Z, R1, and s are defined herein.