(5-Chloro-2-phenylsulfanyl-phenyl)-(3-chloro-propyl)-amine | 180145-03-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (5-Chloro-2-phenylsulfanyl-phenyl)-(3-chloro-propyl)-amine
• CAS: 180145-03-3
• 化学式: C₁₅H₁₅Cl₂NS
• 分子量: 312.263
• InChiKey: WZNPEVHVIFSQJI-UHFFFAOYSA-N

物化性质

• 沸点：
  454.8±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  19.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  12.03
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (5-Chloro-2-phenylsulfanyl-phenyl)-(3-chloro-propyl)-amine 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 3.0h， 生成 (5-Chloro-2-phenylsulfanyl-phenyl)-(3-iodo-propyl)-amine
  参考文献：
  名称：

  2-Amino diphenylsulfides as inhibitors of trypanothione reductase: modification of the side chain

  摘要：

  A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within the synthesized series confirmed the main working hypothesis inspired by the molecular modeling study. The different compounds were tested in vitro on the enzyme and on Trypanosoma cruzi and Trypanosoma brucei trypomastigotes as well as in vivo in infected mice. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00083-1
• 作为产物：
  描述：

  2-氨基-4-氯二苯基硫化物 在 吡啶 、 硼烷 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.33h， 生成 (5-Chloro-2-phenylsulfanyl-phenyl)-(3-chloro-propyl)-amine
  参考文献：
  名称：

  2-Amino diphenylsulfides as inhibitors of trypanothione reductase: modification of the side chain

  摘要：

  A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within the synthesized series confirmed the main working hypothesis inspired by the molecular modeling study. The different compounds were tested in vitro on the enzyme and on Trypanosoma cruzi and Trypanosoma brucei trypomastigotes as well as in vivo in infected mice. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00083-1

文献信息

• Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities
  作者：Bernhard Stump、Christian Eberle、Marcel Kaiser、Reto Brun、R. Luise Krauth-Siegel、François Diederich

  DOI：10.1039/b806371k

  日期：——

  Trypanothione reductase (TR) is an essential enzyme of trypanosomatids and therefore a promising target for the development of new drugs against African sleeping sickness and Chagas' disease. Diaryl sulfides with a central anilino moiety, decorated with a flexible N-alkyl side chain bearing a terminal ammonium ion, are a known class of inhibitors. Using computer modelling, we revised the binding model

  锥虫硫磷还原酶（TR）是锥虫的必不可少的酶，因此是开发抗非洲昏睡病和南美锥虫病新药的有希望的目标。具有中心苯胺基部分并用带有末端铵离子的柔性N-烷基侧链修饰的二芳基硫化物是已知的抑制剂。使用计算机建模，我们修改了这类TR抑制剂的结合模型，预测铵离子封端的N-烷基链与同二聚体第二个亚基的Glu18以及Glu465'/ Glu466'同时相互作用，而疏水取代基苯胺环的一部分在Trp21和Met113附近占据“ mepacrine结合位点”。抑制剂支架的羧酸盐结合片段和二芳基硫醚核的系统性改变为提出的结合模式提供了证据。体外研究表明，对布鲁氏锥虫和疟原虫恶性疟原虫的微摩尔至亚微摩尔范围内的低IC（50）值。