1-(3-azidopropyl)-4-(2-methoxyphenyl)piperazine | 1186236-58-7

• 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-(3-azidopropyl)-4-(2-methoxyphenyl)piperazine
• CAS: 1186236-58-7
• 化学式: C₁₄H₂₁N₅O
• 分子量: 275.354
• InChiKey: LQFGXGXYJIHDGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-azidopropyl)-4-(2-methoxyphenyl)piperazine 、 7,8-dimethoxy-3-(pent-4-ynyl)-1-m-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine 在 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到7,8-dimethoxy-3-(3-(1-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-1,2,3-triazol-4-yl)propyl)-1-m-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine
  参考文献：
  名称：

  ‘Click’ D1 receptor agonists with a 5-HT1A receptor pharmacophore producing D2 receptor activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.06.019
• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 在 sodium azide 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.5h， 生成 1-(3-azidopropyl)-4-(2-methoxyphenyl)piperazine
  参考文献：
  名称：

  2-Amino-3-(1-(4-(4-(2-methoxyphenyl) piperazine-1-yl)butyl)-1H-1,2,3-triazol-4-yl) propanoic acid: synthesized,^99mTc-tricarbonyl labeled, and bioevaluated as a potential 5HT_1Areceptor ligand

  摘要：

  为了开发一种新型 5HT1A 受体成像剂，我们合成了一种新的甲氧基苯基哌嗪衍生物，并用 99mTc-tricarbonyl 前体进行了放射性标记。我们利用 Cu (I) 催化叠氮化物和末端炔烃的环加成反应合成了 1, 2, 3 三唑作为金属螯合体系。这种合成方法提供了将锝连接到甲氧基苯基哌嗪分子上的可靠且可重复的方法。配体的 99mTc 三羰基标记以高放射化学纯度（大于 95%）完成。放射性标记化合物在室温下至少稳定 24 小时。大鼠的生物分布研究显示，注射后 5 分钟，大脑海马吸收率为 0.31 ± 0.02 %ID/g。良好的体外/体内稳定性、亲油性和生物分布特征表明，这种放射性共轭物是进一步探索其潜在临床应用的良好候选物。Copyright © 2012 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.2953

文献信息

• Development of a Focused Library of Triazole-Linked Privileged-Structure-Based Conjugates Leading to the Discovery of Novel Phenotypic Hits against Protozoan Parasitic Infections
  作者：Elisa Uliassi、Lorna Piazzi、Federica Belluti、Andrea Mazzanti、Marcel Kaiser、Reto Brun、Carolina B. Moraes、Lucio H. Freitas-Junior、Sheraz Gul、Maria Kuzikov、Bernhard Ellinger、Chiara Borsari、Maria Paola Costi、Maria Laura Bolognesi

  DOI：10.1002/cmdc.201700786

  日期：2018.4.6

  to generate a focused library of high‐quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME‐tox profiling. Thus, an 18‐membered library was efficiently assembled via Huisgen cycloaddition of phenothiazine, biphenyl, and phenylpiperazine scaffolds. The resulting 18 compounds were then tested against seven parasite strains

  疟原虫，利什曼原虫和锥虫引起的原生动物感染spp。对全世界的传染病负担做出重大贡献，导致严重的发病率和死亡率。现有治疗方法的不足要求进行具有成本效益和时间效益的药物开发。为此，我们设想将特权结构的三唑键连接作为有效的药物设计策略，以生成高质量化合物的重点文库。这种方法的多功能性与表型分析的可行性相结合，并与早期的ADME-tox分析相结合。因此，通过吩噻嗪，联苯和苯基哌嗪支架的Huisgen环加成反应，可以有效地组装一个由18个成员组成的文库。然后对所得的18种化合物针对7种寄生虫菌株进行了测试，并针对两种哺乳动物细胞系进行了反筛选。平行地，h评估了ERG和细胞色素P450（CYP）的抑制作用以及线粒体毒性。值得注意的是，10-（（1-（3-（[[1,1'-联苯] -3-基氧基）丙基）-1 H -1,1,2,3-三唑-5-基）甲基）-10 H-吩噻嗪（7）和10-（3-（1-（3-（[[1
• A general procedure for carbon isotope labeling of linear urea derivatives with carbon dioxide
  作者：Victor Babin、Antoine Sallustrau、Olivier Loreau、Fabien Caillé、Amélie Goudet、Héloïse Cahuzac、Antonio Del Vecchio、Frédéric Taran、Davide Audisio

  DOI：10.1039/d1cc02665h

  日期：——

  Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including 14C and 11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.

  碳同位素标记是一种无痕技术，可以跟踪环境或生物体中有机化合物的命运。本文报告了基于 Staudinger aza-Wittig 序列用所有碳同位素（包括14 C 和11 C）标记尿素衍生物的一般方法。它提供了对所有脂肪族/芳香族尿素组合的访问。
• New^99mTc(CO)₃-radiolabeled arylpiperazine pharmacophore as potent 5HT_1Aserotonin receptor radiotracer: Docking studies, chemical synthesis, radiolabeling, and biological evaluation
  作者：Mostafa Erfani、Hadi Malek、Seyed Esmaeil Sadat Ebrahimi、Leila Hassanzadeh

  DOI：10.1002/jlcr.3709

  日期：2019.4

  In spite of previous efforts, there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain, which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl)piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbon linker and radiolabeled by [99mTc][Tc(CO)3(H2O)3]+ precursor. Docking studies before chemical synthesis showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99mTc(CO)3 group in the structure of new ligand. MPP-(CH2)3-N3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radiolabeled by addition of 2-ethynylpyridine and [99mTc][Tc(CO)3(H2O)3]+ precursor in one pot procedure (more than 95% radiochemical efficiency) through click chemistry method. After incubation, radiotracer was found stable in vitro up to 2 hours. Binding assays showed about 33% specific binding of radiotracer to the 5HT1A receptors. Brain biodistribution studies indicated (0.26 ± 0.05)% ID/g hippocampus uptake at 30 minutes post injection, which its specificity was verified through blocking studies. These results suggested that new designed radioligand might serve as a potent SPECT imaging agent to estimate status of 5HT1A receptors.

  尽管之前做了很多努力，但仍缺乏一种放射性示踪剂来成像人脑中的 5HT1A 受体密度，而这种受体与多种脑神经疾病有关。本研究的目的是制备一种新的 1-(2-甲氧基苯基)哌嗪（MPP）衍生物，作为 5HT1A 受体拮抗剂的主要化学结构，并带有 3 个碳链接，用[99mTc][Tc(CO)3(H2O)3]+ 前体进行放射性标记。化学合成前的对接研究表明，尽管新配体的结构中加入了 99mTc(CO)3 基团，但 WAY100635（强效 5HT1A 受体拮抗剂）和新设计的配体的相互作用方式相似。MPP-(CH2)3-N3 通过三个高效可靠的化学合成步骤合成（收率超过 80%），然后通过点击化学方法，在一锅程序中加入 2-乙炔基吡啶和[99mTc][Tc(CO)3( )3]+ 前体进行放射性标记（放射化学效率超过 95%）。经过培养后，放射性示踪剂在体外的稳定性可达 2 小时。结合试验显示，放射性示踪剂与 5HT1A 受体的特异性结合率约为 33%。脑生物分布研究表明，注射后 30 分钟，海马吸收 ID/g 的比例为 (0.26 ± 0.05)%，其特异性通过阻断研究得到了验证。这些结果表明，新设计的放射性配体可作为一种有效的SPECT成像剂来评估5HT1A受体的状态。
• 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.
• Regioselective Click Chemistry for Construction of Arylpiperazinyl 1,2,3-Triazole Derivative Libraries as Dopamine D₄/D₃Receptor Ligands
  作者：Ju Myung Kwak、Ji Su Moon、Sangei Seo、Jea I Choi、Vasu Sampath、Hee-Yoon Lee、Hun Yeong Koh

  DOI：10.5012/bkcs.2014.35.12.3675

  日期：2014.12.20