1,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]piperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]piperazine
• 化学式: C₂₂H₂₆N₆
• 分子量: 374.489
• InChiKey: SBVUTMQIJNCYIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,4'-(1,4-piperazinediyl)bisbenzonitrile 在 盐酸 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 生成 1,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]piperazine
  参考文献：
  名称：

  Trypanocidal Activity of Conformationally Restricted Pentamidine Congeners

  摘要：

  A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. The compounds were evaluated for trypanocidal activity in vitro and in vivo against one drug-sensitive and three drug-resistant trypanosome isolates. The DNA binding affinity of the compounds was also studied using calf thymus DNA and poly(dA-dT). The nature of the linker influenced the DNA binding affinity as well as the trypanocidal activity of the compounds. trans-1,2-Bis(4-amidinophenoxymethylene)cyclopropane (1) was over 25-fold more potent than pentamidine against the drug-resistant isolate KETRI 243As-10-3, albeit with comparable DNA binding affinity. NN'-Bis(4-amidinophenyl)homopiperazine (8) was the most potent trypanocide in vitro against all four trypanosome isolates studied, but N,N'-bis(4-amidinophenyl)piperazine (6) was the most effective agent in vivo against both drug-sensitive and drug-resistant trypanosomes.

  DOI：

  10.1021/jm020375q

文献信息

• Synthesis and anti-Pneumocystis carinii activity of conformationally restricted analogues of pentamidine
  作者：Bin Tao、Tien L Huang、Qian Zhang、Latasha Jackson、Sherry F Queener、Isaac O Donkor

  DOI：10.1016/s0223-5234(99)80102-0

  日期：1999.6

  A series of conformationally restricted analogues of pentamidine in which the flexible central bridge has been replaced by trans-cyclopropyl, phenyl, pyridinyl, piperazinyl or homopiperazinyl groups as conformationally restricted linkers have been synthesized. The anti-Pneumocystis carinii activity of these compounds was evaluated in a cell culture model and the DNA binding affinity was determined by thermal denaturation measurements. At 1 mu M, compounds 2, 3, 5, 7, 9 and pentamidine were highly effective and caused total inhibition of P. carinii growth in culture. At 0.1 mu M, compounds 2, 5, 7 and 10 were more active than pentamidine with N, N'-bis(4-amidinophenyl)piperazine 7 being approximately 15-fold more effective than pentamidine. The most active compounds, 7 and 10, showed strong binding affinities for calf thymus DNA and poly(dA-dT); however, a clear correlation between DNA binding affinity and the in vitro anti-P. carinii activity of these compounds was not observed. The results suggest that the nature of the central Linker influences the biological actions of these compounds. (C) Elsevier, Paris.
• Trypanocidal Activity of Conformationally Restricted Pentamidine Congeners
  作者：Isaac O. Donkor、Tien L. Huang、Bin Tao、Donna Rattendi、Schennella Lane、Marc Vargas、Burt Goldberg、Cyrus Bacchi

  DOI：10.1021/jm020375q

  日期：2003.3.1

  A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized. The compounds were evaluated for trypanocidal activity in vitro and in vivo against one drug-sensitive and three drug-resistant trypanosome isolates. The DNA binding affinity of the compounds was also studied using calf thymus DNA and poly(dA-dT). The nature of the linker influenced the DNA binding affinity as well as the trypanocidal activity of the compounds. trans-1,2-Bis(4-amidinophenoxymethylene)cyclopropane (1) was over 25-fold more potent than pentamidine against the drug-resistant isolate KETRI 243As-10-3, albeit with comparable DNA binding affinity. NN'-Bis(4-amidinophenyl)homopiperazine (8) was the most potent trypanocide in vitro against all four trypanosome isolates studied, but N,N'-bis(4-amidinophenyl)piperazine (6) was the most effective agent in vivo against both drug-sensitive and drug-resistant trypanosomes.