2-[4-(4-methylphenyl)piperazin-1-yl]ethanamine | 79322-91-1

• 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: 2-[4-(4-methylphenyl)piperazin-1-yl]ethanamine
• 英文别名: 2-(4-p-tolyl-piperazin-1-yl)-ethylamine；1-p-Tolyl-4-(2-aminoethyl)-piperazin
• CAS: 79322-91-1
• 化学式: C₁₃H₂₁N₃
• 分子量: 219.33
• InChiKey: CJJGYUNFHMWIAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-喹喔啉甲酰氯 、 2-[4-(4-methylphenyl)piperazin-1-yl]ethanamine 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 15.0h， 生成 N-{2-[4-(4-methylphenyl)piperazin-1-yl]ethyl}-2-quinoxaline carboxamide
  参考文献：
  名称：

  Chemical Modifications on 4-Arylpiperazine-Ethyl Carboxamide Derivatives Differentially Modulate Affinity for 5-HT1A, D4.2, and α2A Receptors: Synthesis and In Vitro Radioligand Binding Studies

  摘要：

  我们制备了一系列取代的 4-芳基哌嗪-乙基杂芳基羧酰胺，并在体外放射性配体结合研究中进行了测试。喹喔啉的存在对血清素 5-HT1A 与多巴胺 D4.2 受体的选择性具有有利影响。就对 5-HT1A 受体和 D4.2 受体的亲和力和选择性而言，远端苯环上带有 3-CF3 基团的化合物最为有效。用 4-苯基-1,2,3,6-四氢吡啶取代相应的 4-苯基-哌嗪侧链也不仅有利于提高对 5-HT1A 和 D4.2 受体的亲和力，而且在某些情况下还有利于提高对 α 2A 肾上腺素受体的亲和力。

  DOI：

  10.1071/ch09353
• 作为产物：
  描述：

  1-(4-甲基苯基)哌嗪 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[4-(4-methylphenyl)piperazin-1-yl]ethanamine
  参考文献：
  名称：

  ZM241385衍生物在人腺苷A2A受体上的结合动力学

  摘要：

  经典药物的设计和开发主要依赖于亲和力或效价驱动的结构-活性关系（SAR）。迄今为止，给定化合物的结合动力学已被很大程度上忽略，其重要性现在越来越被人们所认识。在本研究中，除了对腺苷A 2A受体（A 2A R）进行传统的SAR分析外，我们还进行了广泛的结构动力学关系（SKR）研究。由24 A 2A R化合物组成的化合物，所有三唑三嗪衍生物均类似于原型拮抗剂ZM241385（4-（2-（（7-氨基-2-（呋喃-2-基）-[1,2,4]三唑[1， 5一] [1,3,5] triazin-5-基）氨基）乙基）苯酚）在亲和力上仅显示微小差异，尽管它们与受体的解离速率差异很大。我们相信，像我们对A 2A R所做的那样，SKR和SAR分析的这种结合对于G蛋白偶联受体的超家族将具有普遍的重要性，因为它可以作为调整配体之间相互作用的新策略和受体。

  DOI：

  10.1002/cmdc.201300474

文献信息

• Design, Synthesis, Lipophilic Properties, and Binding Affinities of Potential Ligands in Positron Emission Tomography (PET) for Visualization of Brain Dopamine D₄Receptors
  作者：Enza Lacivita、Paola De Giorgio、Nicola A. Colabufo、Francesco Berardi、Roberto Perrone、Mauro Niso、Marcello Leopoldo

  DOI：10.1002/cbdv.201300194

  日期：2014.2

  We report the synthesis of compounds structurally related to the high-affinity dopamine D4 receptor ligand N-2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-methoxybenzamide (1e). All compounds were specifically designed as potential PET radioligands for brain D4 receptor visualization, having lipophilicity within a range for brain uptake and weak non-specific binding (0.75100-fold), but its D4

  我们报告了与高亲和力多巴胺D4受体配体N- 2- [4-（3-氰基吡啶-2-基）哌嗪-1-基]乙基} -3-甲氧基苯甲酰胺（1e）相关的化合物的合成。所有化合物均经过专门设计，可用于脑D4受体显像的潜在PET放射性配体，具有一定的亲脂性，可吸收脑部，且弱非特异性结合（0.75100倍），但其D4受体亲和力在脑D4受体成像方面次优（Ki = 30 nM）。
• Design, Synthesis, Radiolabeling, and in Vivo Evaluation of Carbon-11 Labeled <i>N</i>-[2-[4-(3-Cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a Potential Positron Emission Tomography Tracer for the Dopamine D₄ Receptors
  作者：Enza Lacivita、Paola De Giorgio、Irene T. Lee、Sean I. Rodeheaver、Bryan A. Weiss、Claudia Fracasso、Silvio Caccia、Francesco Berardi、Roberto Perrone、Ming-Rong Zhang、Jun Maeda、Makoto Higuchi、Tetsuya Suhara、John A. Schetz、Marcello Leopoldo

  DOI：10.1021/jm100925m

  日期：2010.10.28

  synthesis, and evaluation of physicochemical and pharmacological properties of D4 dopamine receptor ligands related to N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2). Structural features were incorporated to increase affinity for the target receptor, to improve selectivity over D2 and σ1 receptors, to enable labeling with carbon-11 or fluorine-18, and to adjust lipophilicity within

  这里，我们描述的设计，合成，和d的物理化学和药理学性质的评价4相关的多巴胺受体配体ñ - （[2- [4-（4-氯苯基）哌嗪-1-基]乙基] -3-甲氧基苯甲酰胺2）。结合结构特征以增加对目标受体的亲和力，提高对 D 2和 σ 1受体的选择性，能够用碳 11 或氟 18 进行标记，并在被认为最适合脑渗透和低非特异性的范围内调整亲脂性捆绑。化合物7和13显示出总体最佳特性：对 D 4 的纳摩尔亲和力受体，比 D 2和 D 3多巴胺受体、5-HT 1A、5-HT 2A和 5-HT 2C 5-羟色胺受体和 σ 1受体的选择性 > 100 倍，并且 log  P = 2.37-2.55。在小鼠腹膜内给药后，两种化合物迅速进入中枢神经系统。的甲氧基ñ - [2- [4-（3-氰基吡啶-2-基）哌嗪-1-基]乙基] -3-甲氧基苯甲酰胺（7）用碳-11进行放射性标记，并在非人类进行PET分析灵长类动物。[
• Isoxazole Derivatives and Use Thereof
  申请人：Cho Jeong Woo

  公开号：US20090131336A1

  公开（公告）日：2009-05-21

  Disclosed herein are isoxazole derivaties and uses thereof. Serving as agonists of Wnt, the isoxazole derivatives activate Wnt/β-catenin signaling and thus can be used in the treatment and prevention of diseases related to the signal transduction. Also, pharmaceutically acceptable salts of the isoxazole derivatives are disclosed.

  本文披露了异噁唑衍生物及其用途。作为Wnt的激动剂，异噁唑衍生物激活Wnt/β-连环蛋白信号传导，因此可用于治疗和预防与信号传导相关的疾病。此外，还披露了异噁唑衍生物的药用盐。
• Synthesis and biological evaluation of novel T-type Ca2+ channel blockers
  作者：Hee Kyung Jung、Munikumar Reddy Doddareddy、Joo Hwan Cha、Hyewhon Rhim、Yong Seo Cho、Hun Yeong Koh、Bong Young Jung、Ae Nim Pae

  DOI：10.1016/j.bmc.2004.06.011

  日期：2004.8.1

  A small molecule library of piperazinylalkylisoxazole derivatives containing about 600 compounds was designed, synthesized and evaluated for blocking effects on T-type Ca2+ channel. Several ligands were identified to possess high inhibitory activity against the T-type Ca2+ channel. The compound 21 with trifluoromethyl substituents at C-3-position of phenyl group (W) and C-2-position of phenyl group (R-2) showed the highest inhibitory activity with IC50 value of 1.02 muM, which is comparable to that of mibefradil. (C) 2004 Elsevier Ltd. All rights reserved.
• Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain
  作者：Claudio Biancalani、Maria Paola Giovannoni、Stefano Pieretti、Nicoletta Cesari、Alessia Graziano、Claudia Vergelli、Agostino Cilibrizzi、Amalia Di Gianuario、Mariantonella Colucci、Giorgina Mangano、Beatrice Garrone、Lorenzo Polenzani、Vittorio Dal Piaz

  DOI：10.1021/jm900458r

  日期：2009.12.10

  A number of pyridazinone derivatives bearing all arylpiperazinylalkyl chain were synthesized and tested icv in it model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED50 = 3.5 mu g, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting it significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.