3-(5-(3-(dimethylamino)propyl)-10,11-dihydro-5Hdibenzo[b,f]azepine-3-yl)prop-2-yn-1-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-(5-(3-(dimethylamino)propyl)-10,11-dihydro-5Hdibenzo[b,f]azepine-3-yl)prop-2-yn-1-ol
• 英文别名: 3-[11-[3-(Dimethylamino)propyl]-5,6-dihydrobenzo[b][1]benzazepin-2-yl]prop-2-yn-1-ol；3-[11-[3-(dimethylamino)propyl]-5,6-dihydrobenzo[b][1]benzazepin-2-yl]prop-2-yn-1-ol
• 化学式: C₂₂H₂₆N₂O
• 分子量: 334.461
• InChiKey: HOMVSCBTHMQLRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(5-(3-(dimethylamino)propyl)-10,11-dihydro-5Hdibenzo[b,f]azepine-3-yl)prop-2-yn-1-ol 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N,N-dimethyl-3-(3-(3-(2-(2-(naphthalene-1-yl)ethoxy)ethoxy)propyl)-10,11-dihydro-5H-dibenzo[b,f]azepine-5-yl)propane-1-amine
  参考文献：
  名称：

  Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter

  摘要：

  The human serotonin transporter is the primary target of several antidepressant drugs, and the importance of a primary, high affinity binding site (S1) for antidepressant binding is well documented. The existence of a lower affinity, secondary binding site (S2) has, however, been debated. Herein we report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction. Ligand design was inspired by results from docking and steered molecular dynamics simulations, and the ligands were utilized in a structure-activity relationship study of the positional relationship between the S1 and S2 sites. The computer simulations suggested that the S2 site does indeed exist although with lower affinity for imipramine than observed within the S1 site. Additionally, it was possible to dock the 3-linked imipramine analogs into positions which occupy the S1 and the S2 site simultaneously. The structure activity relationship study showed that the shortest ligands were the most potent, and mutations enlarging the proposed S2 site were found to affect the larger ligands positively, while the smaller ligands were mostly unaffected. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.039
• 作为产物：
  描述：

  氯米帕明 在 氯(2-二环己基膦基-2',4′,6′-三异丙基-1,1′-联苯基)[2-(2-氨基乙基)苯基)]钯(II) 、 caesium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 22.42h， 生成 3-(5-(3-(dimethylamino)propyl)-10,11-dihydro-5Hdibenzo[b,f]azepine-3-yl)prop-2-yn-1-ol
  参考文献：
  名称：

  Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter

  摘要：

  The human serotonin transporter is the primary target of several antidepressant drugs, and the importance of a primary, high affinity binding site (S1) for antidepressant binding is well documented. The existence of a lower affinity, secondary binding site (S2) has, however, been debated. Herein we report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction. Ligand design was inspired by results from docking and steered molecular dynamics simulations, and the ligands were utilized in a structure-activity relationship study of the positional relationship between the S1 and S2 sites. The computer simulations suggested that the S2 site does indeed exist although with lower affinity for imipramine than observed within the S1 site. Additionally, it was possible to dock the 3-linked imipramine analogs into positions which occupy the S1 and the S2 site simultaneously. The structure activity relationship study showed that the shortest ligands were the most potent, and mutations enlarging the proposed S2 site were found to affect the larger ligands positively, while the smaller ligands were mostly unaffected. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.039

文献信息

• Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter
  作者：Anne Brinkø、Maja T. Larsen、Heidi Koldsø、Louise Besenbacher、Anders Kolind、Birgit Schiøtt、Steffen Sinning、Henrik H. Jensen

  DOI：10.1016/j.bmc.2016.04.039

  日期：2016.6

  The human serotonin transporter is the primary target of several antidepressant drugs, and the importance of a primary, high affinity binding site (S1) for antidepressant binding is well documented. The existence of a lower affinity, secondary binding site (S2) has, however, been debated. Herein we report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction. Ligand design was inspired by results from docking and steered molecular dynamics simulations, and the ligands were utilized in a structure-activity relationship study of the positional relationship between the S1 and S2 sites. The computer simulations suggested that the S2 site does indeed exist although with lower affinity for imipramine than observed within the S1 site. Additionally, it was possible to dock the 3-linked imipramine analogs into positions which occupy the S1 and the S2 site simultaneously. The structure activity relationship study showed that the shortest ligands were the most potent, and mutations enlarging the proposed S2 site were found to affect the larger ligands positively, while the smaller ligands were mostly unaffected. (C) 2016 Elsevier Ltd. All rights reserved.