3-piperazin-1-ylbenzene-1,2-diamine | 1207461-23-1

• 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: 3-piperazin-1-ylbenzene-1,2-diamine
• 英文别名: 3-(Piperazin-1-yl)benzene-1,2-diamine
• CAS: 1207461-23-1
• 化学式: C₁₀H₁₆N₄
• 分子量: 192.264
• InChiKey: YXKRNDBVASUUSZ-UHFFFAOYSA-N

物化性质

• 沸点：
  417.9±45.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  67.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-piperazin-1-ylbenzene-1,2-diamine 、 萘-1-乙醛 在 ytterbium triflate dihydrate 作用下， 以 二氯甲烷 为溶剂， 以45%的产率得到2-(1-naphthylmethyl)-4-piperazin-1-yl-1H-benzimidazole
  参考文献：
  名称：

  Benzimidazole Derivatives as New Serotonin 5-HT₆ Receptor Antagonists. Molecular Mechanisms of Receptor Inactivation

  摘要：

  On the basis of our previously described pharmacophore model for serotonin 5-HT6 receptor (5-HT6R) antagonists, we have designed, synthesized, and pharmacologically characterized a series of benzimidazole derivatives 1-20 that represent a new family of potent antagonists at the human 5-HT6R. Site-directed mutagenesis and a beta(2)-adrenoceptor-based homology model of the 5-HT6R were used to predict the mode of binding of antagonist SB-258585 and the new synthesized ligands. Substitution of W6.48, F6.52, or N6.55 by Ala fully impedes compound 4 to block 5-HT-induced activation. Thus, we propose that D3.32 in TM 3 anchors the protonated piperazine ring, the benzimidazole, ring expands parallel to EL 2 to hydrogen bond N6.55 in TM 6, and the aromatic ring is placed between TMs 3 and 5 in CH2-containing compounds and between TMs 3 and 6 in CO-containing compounds. This combined experimental and computational study has permitted to propose the molecular mechanisms by which the new benzimidazole derivatives act as 5-HT6R antagonists.

  DOI：

  10.1021/jm901672k
• 作为产物：
  描述：

  2-nitro-3-piperazin-1-ylaniline 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 24.0h， 生成 3-piperazin-1-ylbenzene-1,2-diamine
  参考文献：
  名称：

  Benzimidazole Derivatives as New Serotonin 5-HT₆ Receptor Antagonists. Molecular Mechanisms of Receptor Inactivation

  摘要：

  On the basis of our previously described pharmacophore model for serotonin 5-HT6 receptor (5-HT6R) antagonists, we have designed, synthesized, and pharmacologically characterized a series of benzimidazole derivatives 1-20 that represent a new family of potent antagonists at the human 5-HT6R. Site-directed mutagenesis and a beta(2)-adrenoceptor-based homology model of the 5-HT6R were used to predict the mode of binding of antagonist SB-258585 and the new synthesized ligands. Substitution of W6.48, F6.52, or N6.55 by Ala fully impedes compound 4 to block 5-HT-induced activation. Thus, we propose that D3.32 in TM 3 anchors the protonated piperazine ring, the benzimidazole, ring expands parallel to EL 2 to hydrogen bond N6.55 in TM 6, and the aromatic ring is placed between TMs 3 and 5 in CH2-containing compounds and between TMs 3 and 6 in CO-containing compounds. This combined experimental and computational study has permitted to propose the molecular mechanisms by which the new benzimidazole derivatives act as 5-HT6R antagonists.

  DOI：

  10.1021/jm901672k

文献信息

• Benzimidazole Derivatives as New Serotonin 5-HT₆ Receptor Antagonists. Molecular Mechanisms of Receptor Inactivation
  作者：Tania de la Fuente、Mar Martín-Fontecha、Jessica Sallander、Bellinda Benhamú、Mercedes Campillo、Rocío A. Medina、Lucie P. Pellissier、Sylvie Claeysen、Aline Dumuis、Leonardo Pardo、María L. López-Rodríguez

  DOI：10.1021/jm901672k

  日期：2010.2.11

  On the basis of our previously described pharmacophore model for serotonin 5-HT6 receptor (5-HT6R) antagonists, we have designed, synthesized, and pharmacologically characterized a series of benzimidazole derivatives 1-20 that represent a new family of potent antagonists at the human 5-HT6R. Site-directed mutagenesis and a beta(2)-adrenoceptor-based homology model of the 5-HT6R were used to predict the mode of binding of antagonist SB-258585 and the new synthesized ligands. Substitution of W6.48, F6.52, or N6.55 by Ala fully impedes compound 4 to block 5-HT-induced activation. Thus, we propose that D3.32 in TM 3 anchors the protonated piperazine ring, the benzimidazole, ring expands parallel to EL 2 to hydrogen bond N6.55 in TM 6, and the aromatic ring is placed between TMs 3 and 5 in CH2-containing compounds and between TMs 3 and 6 in CO-containing compounds. This combined experimental and computational study has permitted to propose the molecular mechanisms by which the new benzimidazole derivatives act as 5-HT6R antagonists.