3-(2-nitro-1-(4-(piperidin-1-yl)phenyl)ethyl)-2-phenyl-1H-indole | 1446648-20-9

• 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: 3-(2-nitro-1-(4-(piperidin-1-yl)phenyl)ethyl)-2-phenyl-1H-indole
• 英文别名: 3-[2-nitro-1-(4-piperidin-1-ylphenyl)ethyl]-2-phenyl-1H-indole
• CAS: 1446648-20-9
• 化学式: C₂₇H₂₇N₃O₂
• 分子量: 425.53
• InChiKey: UBADCCWDOFZBPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苯基吲哚 、 1-(4-(2-nitroethyl)phenyl)piperidine 在 三氟甲烷磺酸铵 作用下， 以 乙醇 、 水 为溶剂， 反应 0.58h， 以77%的产率得到3-(2-nitro-1-(4-(piperidin-1-yl)phenyl)ethyl)-2-phenyl-1H-indole
  参考文献：
  名称：

  在三氟乙酸铵存在下，微波促进2-Arylindoles取代β-硝基苯乙烯的共轭加成：一种新型新型CB1大麻素受体变构调节剂的合成方法

  摘要：

  通常，与吲哚类化合物相比，2-Arylindoles类对取代的硝基苯乙烯类化合物的偶联物反应性降低。我们在此报告了在微波辐射下，在三氟乙酸铵存在下，将2-芳基吲哚向取代的β-硝基苯乙烯中进行高效，快速且高产的共轭加成反应的方法。该方法温和，收率高且可重现，与其他亲电试剂相比，对添加β-硝基苯乙烯具有选择性。与传统的加热合成路线相比，从优化的微波方法获得的结果始终在较短的时间内提高了产量。

  DOI：

  10.1002/jhet.2861

文献信息

• [EN] CANNABINOID TYPE 1 RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RÉCEPTEUR CANNABINOÏDE DE TYPE 1
  申请人：UNIV TORONTO

  公开号：WO2016029310A1

  公开（公告）日：2016-03-03

  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.

  本公开涉及公式（I）的吲哚衍生物，这些衍生物是大麻素类型1受体调节剂，对于治疗需要调节受体的疾病是有益的；涉及它们的制备方法；包含它们的药物组合物；以及使用它们的方法。
• [EN] ALLOSTERIC MODULATORS OF CB1 CANNABINOID RECEPTORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS DE CANNABINOÏDES CB1
  申请人：UNIV NORTHEASTERN

  公开号：WO2013103967A1

  公开（公告）日：2013-07-11

  The present invention relates to novel heterocyclic derivatives which are allosteric modulators of cannabinoid receptor 1 (CB1) and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with endocannabinoid dysfunction and diseases in which the CB1 subtype of cannabinoid receptor is involved; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.

  本发明涉及新的杂环衍生物，它们是大麻素受体1（CB1）的别构调节剂，可用于治疗或预防与内源性大麻素功能障碍有关的神经和精神障碍以及涉及大麻素受体CB1亚型的疾病；涉及它们的制备方法；涉及包含它们的制药组合物；以及使用它们的方法。
• ALLOSTERIC MODULATORS OF CB1 CANNABINOID RECEPTORS
  申请人：Northeastern University

  公开号：US20150005346A1

  公开（公告）日：2015-01-01

  The present invention relates to novel heterocyclic derivatives which are allosteric modulators of cannabinoid receptor 1 (CB1) and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with endocannabinoid dysfunction and diseases in which the CB1 subtype of cannabinoid receptor is involved; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.

  本发明涉及新型杂环衍生物，它们是大麻素受体1（CB1）的别构调节剂，并且适用于治疗或预防与内源性大麻素功能障碍和涉及CB1亚型的大麻素受体相关的神经和精神障碍以及疾病；涉及它们的制备方法；涉及包含它们的制药组合物；以及使用它们的方法。
• Allosteric modulators of CB1 cannabinoid receptors
  申请人：Northeastern University

  公开号：US10246414B2

  公开（公告）日：2019-04-02

  The present invention relates to novel heterocyclic derivatives which are allosteric modulators of cannabinoid receptor 1 (CB1) and which are useful for the treatment or prevention of neurological and psychiatric disorders associated with endocannabinoid dysfunction and diseases in which the CB1 subtype of cannabinoid receptor is involved; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.

  本发明涉及新型杂环衍生物，它们是大麻素受体 1（CB1）的异位调节剂，可用于治疗或预防与内源性大麻素功能障碍有关的神经和精神疾病以及涉及大麻素受体 CB1 亚型的疾病；涉及其制备工艺；涉及包含它们的药物组合物；还涉及使用它们的方法。
• Focused structure-activity relationship profiling around the 2-phenylindole scaffold of a cannabinoid type-1 receptor agonist-positive allosteric modulator: site-III aromatic-ring congeners with enhanced activity and solubility
  作者：Peter C. Schaffer、Pushkar M. Kulkarni、David R. Janero、Ganesh A. Thakur

  DOI：10.1016/j.bmc.2020.115727

  日期：2020.11

  Specific tuning of cannabinoid 1 receptor (CB1R) activity by small-molecule allosteric modulators is a therapeutic modality with multiple properties inherently advantageous to therapeutic applications. We previously generated a library of unique CB1R positive allosteric modulators (PAMs) derived from GAT211, which has three pharmacophoric sites critical to its ago-PAM activity. To elaborate our CB1R PAM library, we report the rational design and molecular-pharmacology profiling of several 2-phenylindole analogs modified at the "site-III" aromatic ring. The comprehensive structure-activity relationship (SAR) investigation demonstrates that attaching small lipophilic functional groups on the ortho-position of the GAT211 site-III phenyl ring could markedly enhance CB1R ago-PAM activity. Select site-III modifications also improved GAT211's water solubility. The SAR reported both extends the structural diversity of this compound class and demonstrates the utility of GAT211's site-III for improving the parent compound's drug-like properties of potency and/or aqueous solubility.