1-(9H-carbazol-9-yl)-3-(cyclohexylamino)propan-2-ol | 304893-67-2

• 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-(cyclohexylamino)propan-2-ol
• 英文别名: MB1_A_009063A-4；SJ000550864-1；MMV009063；1-Carbazol-9-yl-3-cyclohexylamino-propan-2-ol；1-carbazol-9-yl-3-(cyclohexylamino)propan-2-ol
• CAS: 304893-67-2
• 化学式: C₂₁H₂₆N₂O
• 分子量: 322.45
• InChiKey: VKKYZYNAWYQWQN-UHFFFAOYSA-N

物化性质

• 沸点：
  548.3±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 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-(cyclohexylamino)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28%的产率得到N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-cyclohexyl-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 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(9H-carbazol-9-yl)-3-(cyclohexylamino)propan-2-ol
  参考文献：
  名称：

  Carbazole-containing arylcarboxamides as BACE1 inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2011.09.064

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.
• 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.