N-(3-aminopropyl)-N-dibenzosuberyl-1,3-diaminopropane

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: N-(3-aminopropyl)-N-dibenzosuberyl-1,3-diaminopropane
• 英文别名: N'-(3-aminopropyl)-N'-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenyl)propane-1,3-diamine
• 化学式: C₂₁H₂₉N₃
• 分子量: 323.481
• InChiKey: AQUJESQKTMSUCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-[3-(trifluoroacetamido)propyl]-N-dibenzosuberyl-N'-trifluoroacetyl-1,3-diaminopropane 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 以96%的产率得到N-(3-aminopropyl)-N-dibenzosuberyl-1,3-diaminopropane
  参考文献：
  名称：

  Dibenzosuberyl substituted polyamines and analogs of clomipramine as effective inhibitors of trypanothione reductase; molecular docking, and assessment of trypanocidal activities

  摘要：

  Trypanothione reductase (TR) is an enzyme critical to the maintenance of the thiol redox balance in trypanosomatids, including the genera Trypanosoma and Leishmania that are parasites responsible for several serious diseases. Analogs of clomipramine were prepared since clomipramine is reported to inhibit TR and cure mice infected with trypanosomes, however its psychotropic activity precludes its use as an anti-trypanosomal therapeutic. The clomipramine analogs contained a tricyclic dibenzosuberyl moiety. Additionally a series of polyamines with N-dibenzosuberyl substituents were prepared. All compounds studied were competitive inhibitors of TR and showed trypanocidal activities against Trypanosoma brucei in vitro. The analogs of clomipramine were poor inhibitors of TR, whereas the polyamine derivatives were effective TR inhibitors with the most potent compound, N-4, N-8-bis(dibenzosuberyl) spermine (7), having a K-i value of 0.26 mu M. However, compound (7) did not prolong the lives of mice infected with trypanosomes. Analysis of docking studies indicated: the tricyclic groups of inhibitors bind at four distinct hydrophobic regions in the active site of TR; the importance of the chlorine substituent of clomipramine in binding to TR; and binding of the dibenzosuberyl groups of (7) occur at separate and distinct hydrophobic regions within the active site of TR. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.018

文献信息

• Dibenzosuberyl substituted polyamines and analogs of clomipramine as effective inhibitors of trypanothione reductase; molecular docking, and assessment of trypanocidal activities
  作者：Mary C. O’Sullivan、Timothy B. Durham、Hannah E. Valdes、Kelly L. Dauer、Nicholas J. Karney、Andrew C. Forrestel、Cyrus J. Bacchi、Jerome F. Baker

  DOI：10.1016/j.bmc.2015.01.018

  日期：2015.3

  Trypanothione reductase (TR) is an enzyme critical to the maintenance of the thiol redox balance in trypanosomatids, including the genera Trypanosoma and Leishmania that are parasites responsible for several serious diseases. Analogs of clomipramine were prepared since clomipramine is reported to inhibit TR and cure mice infected with trypanosomes, however its psychotropic activity precludes its use as an anti-trypanosomal therapeutic. The clomipramine analogs contained a tricyclic dibenzosuberyl moiety. Additionally a series of polyamines with N-dibenzosuberyl substituents were prepared. All compounds studied were competitive inhibitors of TR and showed trypanocidal activities against Trypanosoma brucei in vitro. The analogs of clomipramine were poor inhibitors of TR, whereas the polyamine derivatives were effective TR inhibitors with the most potent compound, N-4, N-8-bis(dibenzosuberyl) spermine (7), having a K-i value of 0.26 mu M. However, compound (7) did not prolong the lives of mice infected with trypanosomes. Analysis of docking studies indicated: the tricyclic groups of inhibitors bind at four distinct hydrophobic regions in the active site of TR; the importance of the chlorine substituent of clomipramine in binding to TR; and binding of the dibenzosuberyl groups of (7) occur at separate and distinct hydrophobic regions within the active site of TR. (C) 2015 Elsevier Ltd. All rights reserved.