1-(2-methoxyphenyl)-4-(pent-4-yn-1-yl)-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-(2-methoxyphenyl)-4-(pent-4-yn-1-yl)-piperazine
• 英文别名: 1-(2-methoxyphenyl)-4-(pent-4-ynyl)piperazine；1-(2-methoxyphenyl)-4-(pentyn-4-yl)piperazine；1-(2-Methoxyphenyl)-4-pent-4-ynylpiperazine；1-(2-methoxyphenyl)-4-pent-4-ynylpiperazine
• 化学式: C₁₆H₂₂N₂O
• 分子量: 258.363
• InChiKey: PCXRJKYDOAQMRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-methoxyphenyl)-4-(pent-4-yn-1-yl)-piperazine 、 叠氮苯 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 8.25h， 以60%的产率得到1-(2-methoxyphenyl)-4-(3-(1-phenyl-1H-1,2,3-triazol-4-yl)propyl)piperazine
  参考文献：
  名称：

  Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands

  摘要：

  A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D-2 and D-3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D-3 receptors and moderate selectivity for the dopamine D-3 versus D-2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D-2 and D-3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D-4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D-2 and D-3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D-3 receptors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.023
• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 、 5-碘-1-戊炔 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以80%的产率得到1-(2-methoxyphenyl)-4-(pent-4-yn-1-yl)-piperazine
  参考文献：
  名称：

  通过使用原位点击化学的方法，HIV-1蛋白酶的抑制剂。

  摘要：

  DOI：

  10.1002/anie.200502161

文献信息

• Preparation, Characterization, and Screening of a High Affinity Organometallic Probe for α-Adrenergic Receptors
  作者：Anika S. Louie、Neil Vasdev、John F. Valliant

  DOI：10.1021/jm2001162

  日期：2011.5.12

  derivative, for which a single crystal X-ray structure was obtained, showed high and selective affinity toward α1A, α1D, and α2C adrenergic receptors with Ki values of 17, 21, and 39 nM, respectively. A method to prepare the corresponding 99mTc complex was also developed where the resulting metallocarborane was shown to be stable and is therefore suitable for in vivo molecular imaging studies.

  据报道，有机金属rh络合物对α-肾上腺素能受体具有高选择性的亲和力。制备了一系列与[Re（CO）3 ] +核络合的甲氧基苯基哌嗪甲硼烷配体，并筛选了所产生的有机金属化合物与5-羟色胺，σ和肾上腺素能受体以及多巴胺，5-羟色胺和去甲肾上腺素转运蛋白的结合。酰胺联衍生物，得到了用于其的单晶X射线结构，表现出对α和高选择性亲和力1A，α 1D，α 2C肾上腺素能受体与ķ我值分别为17，21，和39纳米。一种准备相应的99m的方法还开发了Tc络合物，其中所得的金属碳硼烷被证明是稳定的，因此适用于体内分子成像研究。
• Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands
  作者：Na Ye、QianQian Wu、Liyuan Zhu、Longtai Zheng、Bo Gao、Xuechu Zhen、Ao Zhang

  DOI：10.1016/j.bmc.2011.01.053

  日期：2011.3

  A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D-3 receptor, low or no affinity at the D-1 and D-2 receptors. Compounds 7f and 11c stood out as the most potent at the D-3 receptor among our newly synthesized aporlogues with K-i values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT1A receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with K-i values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D-3 over 5-HT1A receptors. Such D-3/5-HT1A dual property of these compounds may be useful in the treatment of several brain disorders. (C) 2011 Elsevier Ltd. All rights reserved.
• ‘Click’ D1 receptor agonists with a 5-HT1A receptor pharmacophore producing D2 receptor activity
  作者：Jing Zhang、Hai Zhang、Wenxian Cai、Leiping Yu、Xuechu Zhen、Ao Zhang

  DOI：10.1016/j.bmc.2009.06.019

  日期：2009.7

  A series of new 1-aryl-3-benzazepine derivatives containing an arylpiperazinyl function as the N3 substituent were synthesized by combining a D-1 receptor agonistic pharmacophore and a 5-HT1A receptor pharmacophore through Click reaction. Interestingly, these compounds generally do not have good binding affinity at the D-1 receptor, but most compounds are potent at both D-2 and 5-HT1A receptors. Compound 8h, containing 1-m-tolyl-benzazepine scaffold and 2-methoxyphenylpiperazine core, displayed good affinity at all tested receptors, with K-i values of 144, 80, and 133 nM, for the D-1, D-2, and 5-HT1A receptors, respectively. Compound 13 with the triazole moiety formed differently from that in 8h showed the highest affinity at the D-2 receptor with K-i value of 19 nM. This compound also showed moderate affinity at the 5-HT1A (K-i, 105 nM), and D-1 (K-i, 551 nM) receptors. Functional assays indicated that both compounds 13 and 8h are antagonists at D-1 and D-2 receptors, whereas full agonistic activity at the 5-HT1A receptor was observed. In agreement with the binding affinity, compound 13 is a high efficacy D-2 antagonist and 5-HT1A agonist. (C) 2009 Elsevier Ltd. All rights reserved.
• 1,4-Disubstituted aromatic piperazines with high 5-HT2A/D2 selectivity: Quantitative structure-selectivity investigations, docking, synthesis and biological evaluation
  作者：Dorothee Möller、Ismail Salama、Ralf C. Kling、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmc.2015.07.050

  日期：2015.9

  Simultaneous targeting of dopamine D-2 and 5-HT2A receptors for the treatment of schizophrenia is one key feature of typical and atypical antipsychotics. In most of the top-selling antipsychotic drugs like aripiprazole and risperidone, high affinity to both receptors can be attributed to the presence of 1,4-disubstituted aromatic piperazines or piperidines as primary receptor recognition elements. Taking advantage of our in-house library of phenylpiperazine-derived dopamine receptor ligands and experimental data, we established highly significant CoMFA and CoMSIA models for the prediction of 5-HT2A over D-2 selectivity. Subsequently, the models were applied to identify the selective candidates 55-57 from our newly synthesized library of GPCR ligands comprising a pyrazolo[1,5-a]pyridine head group and a 1,2,3-triazole based linker unit. The test compound 57 showed subnanomolar a K-i value (0.64 nM) for 5-HT2A and more than 10- and 30-fold selectivity over the dopamine receptor isoforms D-2S and D-2L, respectively. (c) 2015 Elsevier Ltd. All rights reserved.
• Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands
  作者：Xin Peng、Qi Wang、Yogesh Mishra、Jinbin Xu、David E. Reichert、Maninder Malik、Michelle Taylor、Robert R. Luedtke、Robert H. Mach

  DOI：10.1016/j.bmcl.2014.12.023

  日期：2015.2

  A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D-2 and D-3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D-3 receptors and moderate selectivity for the dopamine D-3 versus D-2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D-2 and D-3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D-4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D-2 and D-3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D-3 receptors. (C) 2014 Elsevier Ltd. All rights reserved.