α-(aminomethyl)-4-[2-(1-methoxy)phenyl]-1-piperazineethanol | 217170-70-2

• 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: α-(aminomethyl)-4-[2-(1-methoxy)phenyl]-1-piperazineethanol
• 英文别名: 1-Piperazineethanol, alpha-(aminomethyl)-4-(2-methoxyphenyl)-；1-amino-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-ol
• CAS: 217170-70-2
• 化学式: C₁₄H₂₃N₃O₂
• 分子量: 265.356
• InChiKey: NXALKUMQNRTWOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  α-(aminomethyl)-4-[2-(1-methoxy)phenyl]-1-piperazineethanol 在 二乙胺基三氟化硫 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 2-[4-(2-Methoxy-phenyl)-piperazin-1-ylmethyl]-2,3-dihydro-oxazolo[2,3-b]quinazolin-5-one
  参考文献：
  名称：

  1,3-双官能化氨基-2-丙醇与DAST反应中喹唑啉IX：1氟化与1,2-迁移的研究

  摘要：

  通过拟议的螺-叠氮鎓中间体，用DAST诱导的1,2-迁移，处理1-邻苯二甲酰基氨基-3- [4-（2-甲氧基苯基）哌嗪-1-基]-丙醇（7），得到N- [2-氟-3- [4-（2-甲氧基苯基）哌嗪-1-基]丙基]-邻苯二甲酰亚胺（11a），产率为13％，N- [2-氟甲基-2- [4-（2-甲氧基苯基）-哌嗪-1] -基]乙基]邻苯二甲酰亚胺（11b），产率为73％。

  DOI：

  10.1016/s0040-4039(98)01905-4
• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 在 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 87.0h， 生成 α-(aminomethyl)-4-[2-(1-methoxy)phenyl]-1-piperazineethanol
  参考文献：
  名称：

  一些新型氨基醇吡咯并[1,2-a]喹喔啉衍生物的设计，合成及抗疟活性

  摘要：

  在我们寻找抗疟化合物之后，从2-硝基苯胺或2-氨基-3-硝基苯酚合成了一系列新的哌嗪基醇吡咯并[1,2-a]喹喔啉衍生物1-2，并在W2的红细胞生成阶段对其体外活性进行了测试。和3D7恶性疟原虫菌株。生物学结果显示良好的抗疟活性，IC50为0.3至21.1 µM。在尝试研究这些吡咯并[1,2-a]喹喔啉衍生物的广谱抗原生动物活性时，还研究了它们对利什曼原虫donovani的前鞭毛体形式的特性，并揭示了它们的选择性抗血浆特性。同时，在人HepG2细胞系上评估了这些分子的体外细胞毒性。本文讨论了这些新合成化合物的构效关系。

  DOI：

  10.2174/1570180813666160517164758

文献信息

• Synthesis of new piperazinyl-pyrrolo[1,2-<i>a</i>]quinoxaline derivatives as inhibitors of <i>Candida albicans</i> multidrug transporters by a Buchwald–Hartwig cross-coupling reaction
  作者：Jean Guillon、Shweta Nim、Stéphane Moreau、Luisa Ronga、Solène Savrimoutou、Elisabeth Thivet、Mathieu Marchivie、Attilio Di Pietro、Rajendra Prasad、Marc Le Borgne

  DOI：10.1039/c9ra09348f

  日期：——

  Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald–Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of two Candida albicans transporters.

  通过Buchwald–Hartwig交叉偶联反应制备了两系列哌嗪基吡咯并喹啉衍生物，然后评估了它们抑制两种白念珠菌转运体药物外流活性的能力。
• Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α1D/1A-adrenoceptor antagonist and homology modelling
  作者：Junjun Huang、Ran Chen、Yajian Huang、Hang Zhang、Anran Zheng、Qing Xiao、Dan Wu、Ruxia Duan、Zhi Zhou、Fei He、Wei Yi

  DOI：10.1016/j.cclet.2024.109594

  日期：2024.2

  are caused by the subtype nonselective nature or low selectivity of many current drugs. We previously reported that phenylpiperazine analogues with amide and propane linker were moderate adrenoceptor antagonists and exhibited better anti-BPH effect than lead compound naftopidil (NAF) , however, with modest -subtype selectivity. Herein, we replaced propane moiety with 2-hydroxypropanol linker and synthesized

  -肾上腺素能受体（AR）阻滞剂可有效治疗良性前列腺增生/下尿路症状（BPH/LUTS），但其使用受到心血管相关副作用的限制，这些副作用是由亚型非选择性或低选择性引起的目前的许多药物。我们之前报道，带有酰胺和丙烷连接体的苯基哌嗪类似物是中等的肾上腺素受体拮抗剂，并且比先导化合物萘哌地尔（NAF）表现出更好的抗BPH作用，但具有适度的亚型选择性。在此，我们用2-羟基丙醇连接基取代丙烷部分，合成了27种带有修饰的芳香族和杂芳香族基团的外消旋衍生物。在这些新化合物中，喹啉替代物在基于细胞的钙测定和基于组织的功能测定中均表现出极弱的拮抗亲和力，从而引发了显着的选择性。有趣的是，与-相比，对映异构体在大鼠模型中优先表现出更好的抗BPH作用，支持配体以高度立体特异性的方式调节受体。最后，还进行了计算机辅助建模研究，以深入了解-的独特结合模式以及-的亚型受体选择性，该研究也在本研究中得到合理化。总而言之，我们的工作丰富了用于治疗
• Design, synthesis and biological evaluation of pyridine-phenylpiperazines: A novel series of potent and selective α1a-adrenergic receptor antagonist
  作者：Gee-Hong Kuo、Catherine Prouty、William V Murray、Virginia Pulito、Linda Jolliffe、Peter Cheung、Sally Varga、Mary Evangelisto、Charles Shaw

  DOI：10.1016/s0968-0896(00)00151-6

  日期：2000.9

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers displayed comparable potency and better selectivity at alpha(1a)-AR. The S-hydroxy enantiomer 17 (K-i = 0.79 nM; alpha(1b)/alpha(1a) = 800; alpha(1d)/alpha(1a) = 104) was slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1b)/alpha(1a) = 15, alpha(1d)/alpha(1a) = 1.4). Compound 17 displayed higher selectivity in inhibiting rat prostate contraction over rat aorta contraction and also exhibited a higher degree of uroselectivity than tamsulosin in the anesthetized dog model. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Design, Synthesis, and Structure−Activity Relationships of Phthalimide-Phenylpiperazines:  A Novel Series of Potent and Selective α₁_a-Adrenergic Receptor Antagonists
  作者：Gee-Hong Kuo、Catherine Prouty、William V. Murray、Virginia Pulito、Linda Jolliffe、Peter Cheung、Sally Varga、Mary Evangelisto、Jian Wang

  DOI：10.1021/jm9905918

  日期：2000.6.1

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K-i = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a) >5690, >6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1d)/alpha(1a)= 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.
• US5932584A
  申请人：——

  公开号：US5932584A

  公开（公告）日：1999-08-03