4-[4-(2-methoxyphenyl)piperazin-1-yl]phenylamine | 252964-75-3

• 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: 4-[4-(2-methoxyphenyl)piperazin-1-yl]phenylamine
• 英文别名: 4-[4-(2-methoxyphenyl)piperazin-1-yl]aniline；4-(4-(2-Methoxyphenyl)piperazin-1-yl)aniline
• CAS: 252964-75-3
• 化学式: C₁₇H₂₁N₃O
• 分子量: 283.373
• InChiKey: PLZOYODWWIFGJD-UHFFFAOYSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  498.8±45.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-(2-methoxyphenyl)piperazin-1-yl]phenylamine 、 氯甲酸乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%的产率得到N-{4-[4-(2-methoxyphenyl)piperazin-1-yl]phenyl}carbamic acid ethyl ester
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of new arylpiperazines N-{4-[4-(aryl) piperazine-1-yl]-phenyl}-amine derivatives: Putative role of 5-HT1A receptors

  摘要：

  In an attempt to design novel 5-HT1A agonists/partial agonists, based on an arylpiperazine nucleus, a series of N-{4-[4-(aryl) piperazine-1-yl]-phenyl}-amine derivatives were synthesized and biologically tested. The anxiolytic effect of the compounds was investigated employing the Elevated plus Maze (EPM) task. On the basis of in vivo functional test, compound 1c (3 mg/kg) and 4c (3 mg/kg) induced significant increments in open arm entries and time on EPM as compared to Buspirone. The anxiolytic effects of compounds 1c and 4c were effectively antagonized by WAY-100635, a 5-HT1A receptor antagonist (0.5 mg/kg). Furthermore, we have also evaluated the concentration of 5-HT in the brain tissue using HPLC with fluorescent detection. Our result showed that serotonin levels were significantly decreased by similar to 38% (p < 0.001) and similar to 32% (p < 0.001) after acute administration of compounds 1c and 4c, respectively. These findings suggest that the anxiolytic like activity of these new arylpiperazines is mediated via 5-HT1A receptors in the brain. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.043
• 作为产物：
  描述：

  1-(2-methoxyphenyl)-4-(4-nitrophenyl)piperazine 在 盐酸 、 tin 作用下， 以98 %的产率得到4-[4-(2-methoxyphenyl)piperazin-1-yl]phenylamine
  参考文献：
  名称：

  强效新合成乙酰胆碱酯酶抑制剂的结构活性和结合方向分析

  摘要：

  在基于配体的药物设计方法中，合成了十四种新型N-苄基哌啶和N,N-二芳基哌嗪偶联物，并作为多奈哌齐类似物进行了药理学评估。所有化合物都具有高到中度的体外抑制活性，IC 50在 2.3–20 µM 范围内，并且对乙酰胆碱酯酶具有选择性，同时对丁酰胆碱酯酶没有活性。构效关系分析揭示了N,N-二芳基哌嗪部分和连接两个药效团的接头对抑制活性的影响。两种最活跃的化合物7g和8g的动力学研究(IC 50 = 2.3 和 4 µM，分别）揭示了混合型抑制模式，与游离酶和酶-底物复合物结合。为了进一步了解作用机制和结合方向，对所有化合物进行了分子对接，同时对7g和8g进行了配体转运模拟和分子动力学模拟。计算结果很好地证实了体外活性和动力学研究。

  DOI：

  10.1016/j.molstruc.2022.134809

文献信息

• RADIOLABELED COMPOUNDS
  申请人：Hoffmann-La Roche Inc.

  公开号：US20200316232A1

  公开（公告）日：2020-10-08

  The present invention relates to radiolabeled compounds of formula I wherein either A, B, R 1 , R 2 , is labeled with a radionuclide selected from 3 H, C and 18 F and its use for imaging alpha synuclein and/or Abeta deposits in mammals.
• Synthesis and pharmacological evaluation of new arylpiperazines N-{4-[4-(aryl) piperazine-1-yl]-phenyl}-amine derivatives: Putative role of 5-HT1A receptors
  作者：Manisha Khatri、Santosh Kumar Rai、Sameena Alam、Anjana Vij、Manisha Tiwari

  DOI：10.1016/j.bmc.2009.01.043

  日期：2009.3

  In an attempt to design novel 5-HT1A agonists/partial agonists, based on an arylpiperazine nucleus, a series of N-4-[4-(aryl) piperazine-1-yl]-phenyl}-amine derivatives were synthesized and biologically tested. The anxiolytic effect of the compounds was investigated employing the Elevated plus Maze (EPM) task. On the basis of in vivo functional test, compound 1c (3 mg/kg) and 4c (3 mg/kg) induced significant increments in open arm entries and time on EPM as compared to Buspirone. The anxiolytic effects of compounds 1c and 4c were effectively antagonized by WAY-100635, a 5-HT1A receptor antagonist (0.5 mg/kg). Furthermore, we have also evaluated the concentration of 5-HT in the brain tissue using HPLC with fluorescent detection. Our result showed that serotonin levels were significantly decreased by similar to 38% (p < 0.001) and similar to 32% (p < 0.001) after acute administration of compounds 1c and 4c, respectively. These findings suggest that the anxiolytic like activity of these new arylpiperazines is mediated via 5-HT1A receptors in the brain. (C) 2009 Elsevier Ltd. All rights reserved.
• Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors
  作者：Mihajlo J. Krunić、Jelena Z. Penjišević、Relja V. Suručić、Sandra Šegan、Slađana V. Kostić-Rajačić、Ivana I. Jevtić

  DOI：10.1016/j.molstruc.2022.134809

  日期：2023.3

  IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type

  在基于配体的药物设计方法中，合成了十四种新型N-苄基哌啶和N,N-二芳基哌嗪偶联物，并作为多奈哌齐类似物进行了药理学评估。所有化合物都具有高到中度的体外抑制活性，IC 50在 2.3–20 µM 范围内，并且对乙酰胆碱酯酶具有选择性，同时对丁酰胆碱酯酶没有活性。构效关系分析揭示了N,N-二芳基哌嗪部分和连接两个药效团的接头对抑制活性的影响。两种最活跃的化合物7g和8g的动力学研究(IC 50 = 2.3 和 4 µM，分别）揭示了混合型抑制模式，与游离酶和酶-底物复合物结合。为了进一步了解作用机制和结合方向，对所有化合物进行了分子对接，同时对7g和8g进行了配体转运模拟和分子动力学模拟。计算结果很好地证实了体外活性和动力学研究。