1-(9H-carbazol-9-yl)-3-[(2-phenylethyl)amino]propan-2-ol | 301160-11-2

• 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: 1-(9H-carbazol-9-yl)-3-[(2-phenylethyl)amino]propan-2-ol
• 英文别名: 1-(carbazol-9-yl)-3-(2-phenylethylamino)propan-2-ol；1-Carbazol-9-yl-3-phenethylamino-propan-2-ol；1-carbazol-9-yl-3-(2-phenylethylamino)propan-2-ol
• CAS: 301160-11-2
• 化学式: C₂₃H₂₄N₂O
• 分子量: 344.456
• InChiKey: ULYPFEFNGKFKSF-UHFFFAOYSA-N

物化性质

• 沸点：
  571.8±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(9H-carbazol-9-yl)-3-[(2-phenylethyl)amino]propan-2-ol 、 4-氯苯磺酰氯 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以13%的产率得到N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-phenethyl-4-chloro-benzenesulfonamide
  参考文献：
  名称：

  Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors

  摘要：

  A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylsulfonamides has been synthesized and assayed for beta-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl sub-stituents on the nitrogen atom of the arylsulfonamide moiety has so far led to the best results, with three derivatives showing IC50 values ranging from 1.6 to 1.9 mu M. Therefore, a significant improvement over the previously reported series of N-carboxamides (displaying IC50's >= 2.5 mu M) has been achieved, thus suggesting an active role of the sulfonamido-portion in the inhibition process. Preliminary molecular modeling studies have been carried out to rationalize the observed structure-activity relationships. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.09.058
• 作为产物：
  描述：

  咔唑 在 potassium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 37.0h， 生成 1-(9H-carbazol-9-yl)-3-[(2-phenylethyl)amino]propan-2-ol
  参考文献：
  名称：

  新系列卡维地洛衍生物的设计、合成和生物学评估，通过阻断机械电传感器通道保护感觉毛细胞免受氨基糖苷类诱导的损伤。

  摘要：

  氨基糖苷类 (AG) 是用于治疗严重细菌感染的广谱抗生素，但具有限制使用的副作用，包括不可逆的听力损失。在这里，我们评估了卡维地洛在小鼠耳蜗培养和体内斑马鱼试验中的耳保护特性，并研究了它的保护机制，我们发现这可能是由毛细胞的机电传感器 (MET) 通道（主要进入途径）的阻断介导的对于 AG。为了了解卡维地洛的全部耳部保护潜力，制备了一系列 18 种类似物，并评估了它们对 AG 引起的损伤的作用以及它们对 MET 通道的亲和力。发现一种衍生物在耳蜗培养中比卡维地洛本身具有更大的保护作用，并且与 MET 通道的结合更紧密。

  DOI：

  10.1021/acs.jmedchem.8b01325

文献信息

• Carbazole-containing arylcarboxamides as BACE1 inhibitors
  作者：Simone Bertini、Valentina Asso、Elisa Ghilardi、Carlotta Granchi、Clementina Manera、Filippo Minutolo、Giuseppe Saccomanni、Andrea Bortolato、Jonathan Mason、Stefano Moro、Marco Macchia

  DOI：10.1016/j.bmcl.2011.09.064

  日期：2011.11

  beta-Secretase (BACE1) is widely recognized as a prime drug target for the treatment of Alzheimer's disease (AD). In this Letter, we report the synthesis and the BACE1 inhibitory activity of novel, variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylcarboxamides. The best results have been obtained with the introduction of a 4-OMe substituent (IC50 = 3.8 mu M) or a 3,4-dichloro substituent (IC50 = 2.5 mu M) in the amidic aromatic ring. The blood-brain barrier penetration predictions resulted to be promising for this type of compounds. To better understand the structure-activity relationships (SAR) of the new derivatives, a docking study procedure has been applied exploiting different conformational and ionic states of BACE1. (C) 2011 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of a New Series of Carvedilol Derivatives That Protect Sensory Hair Cells from Aminoglycoside-Induced Damage by Blocking the Mechanoelectrical Transducer Channel
  作者：Molly O’Reilly、Nerissa K. Kirkwood、Emma J. Kenyon、Rosemary Huckvale、Daire M. Cantillon、Simon J. Waddell、Simon E. Ward、Guy P. Richardson、Corné J. Kros、Marco Derudas

  DOI：10.1021/acs.jmedchem.8b01325

  日期：2019.6.13

  we found, may be mediated by a block of the hair cell's mechanoelectrical transducer (MET) channel, the major entry route for the AGs. To understand the full otoprotective potential of carvedilol, a series of 18 analogues were prepared and evaluated for their effect against AG-induced damage as well as their affinity for the MET channel. One derivative was found to confer greater protection than carvedilol

  氨基糖苷类 (AG) 是用于治疗严重细菌感染的广谱抗生素，但具有限制使用的副作用，包括不可逆的听力损失。在这里，我们评估了卡维地洛在小鼠耳蜗培养和体内斑马鱼试验中的耳保护特性，并研究了它的保护机制，我们发现这可能是由毛细胞的机电传感器 (MET) 通道（主要进入途径）的阻断介导的对于 AG。为了了解卡维地洛的全部耳部保护潜力，制备了一系列 18 种类似物，并评估了它们对 AG 引起的损伤的作用以及它们对 MET 通道的亲和力。发现一种衍生物在耳蜗培养中比卡维地洛本身具有更大的保护作用，并且与 MET 通道的结合更紧密。
• Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors
  作者：Simone Bertini、Elisa Ghilardi、Valentina Asso、Filippo Minutolo、Simona Rapposelli、Maria Digiacomo、Giuseppe Saccomanni、Veronica Salmaso、Mattia Sturlese、Stefano Moro、Marco Macchia、Clementina Manera

  DOI：10.1016/j.bmcl.2017.09.058

  日期：2017.11

  A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylsulfonamides has been synthesized and assayed for beta-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl sub-stituents on the nitrogen atom of the arylsulfonamide moiety has so far led to the best results, with three derivatives showing IC50 values ranging from 1.6 to 1.9 mu M. Therefore, a significant improvement over the previously reported series of N-carboxamides (displaying IC50's >= 2.5 mu M) has been achieved, thus suggesting an active role of the sulfonamido-portion in the inhibition process. Preliminary molecular modeling studies have been carried out to rationalize the observed structure-activity relationships. (C) 2017 Elsevier Ltd. All rights reserved.