4-(2-甲氧基苯基)-N-2-吡啶基-1-哌嗪乙酰胺 | 146714-63-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(2-甲氧基苯基)-N-2-吡啶基-1-哌嗪乙酰胺
• 英文名称: 4-(2-methoxyphenyl)-1-(2-pyridinylaminocarbonyl)methylpiperazine
• 英文别名: 2-(4-(2-methoxyphenyl)piperazin-1-yl)-N-(pyridin-2-yl)acetamide；2-(1-(4-(2-methoxyphenyl)piperazinyl))-N-(2-pyridyl)acetamide；WAY100635；N-2-[2-{4-(2-methoxyphenyl)-1-piperazinyl}ethyl]amidopyridine；4-(2-Methoxyphenyl)-N-2-pyridinyl-1-piperazineacetamide；2-[4-(2-methoxyphenyl)piperazin-1-yl]-N-pyridin-2-ylacetamide
• CAS: 146714-63-8
• 化学式: C₁₈H₂₂N₄O₂
• 分子量: 326.398
• InChiKey: DBPWHBFPTPHVLC-UHFFFAOYSA-N

物化性质

• 熔点：
  73-75oC
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2-甲氧基苯基)-N-2-吡啶基-1-哌嗪乙酰胺 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 N-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-2-吡啶基-环己烷羧胺
  参考文献：
  名称：

  Screening of 5-HT_1A Receptor Antagonists using Molecularly Imprinted Polymers

  摘要：

  Molecular imprinting produces network polymers with recognition sites for imprint molecules. The high binding affinity and selectivity in conjunction with the polymers' physical robustness positions molecular imprinted polymers (MIPs) as candidates for use as preliminary screens in drug discovery. As such, MIPs can serve as crude mimics of native receptors. In an effort to evaluate the relationship between MIPs and native receptors, imprinted polymers for WAY-100635, an antagonist of the serotonin (5-HT) receptor subtype 5-HT1A were prepared. The resulting MIP P(WAY) was evaluated as an affinity matrix in the screening of serotonin receptor antagonists with known affinities for the native receptor. Rough correlations in affinity between the synthetic P(WAY) and native receptor 5-HT1A were found. These findings provide some support for the analogy between MIPs and native receptors and their possible use as surrogates.

  DOI：

  10.1021/ja067276c
• 作为产物：
  描述：

  2-氨基吡啶 在 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-甲氧基苯基)-N-2-吡啶基-1-哌嗪乙酰胺
  参考文献：
  名称：

  N- {2- [4-（2-甲氧基苯基）哌嗪-1-基]乙基} -N-（吡啶-2-基）环己烷甲酰胺的桥头碘化类似物的设计，合成，放射标记以及体外和体内评价（WAY-100635）作为5-HT 1A受体的潜在SPECT配体

  摘要：

  在这里，我们描述与1（WAY-100635）相关的5-HT 1A受体配体的设计，合成和药理学特征。在环己基部分1和其O形脱甲基类似物3是由桥头碘化桥接稠环替代：金刚烷基，cubyl，双环[2.2.2]辛基，或二环[2.2.1]庚基。在体外，所有类似物均对5-HT 1A受体表现出（亚）纳摩尔亲和力。化合物6b和7b似乎对该受体具有比其他相关受体更高的选择性，并且可以很容易地用放射性碘123碘化。在人肝细胞中，[ 123 I] 6b表现出较低的酰胺水解倾向和稳定的碳碘键。[ 123 I] 6b和[ 123 I] 7b在大鼠中的生物分布表明，碳碘键在体内也很稳定。不幸的是，两种放射性配体的脑摄取和特异性均显着低于母体分子1。总之，设计的示踪剂不适用于SPECT成像。

  DOI：

  10.1021/jm1009956

文献信息

• Copper-Mediated Radiofluorination of Arylstannanes with [¹⁸F]KF
  作者：Katarina J. Makaravage、Allen F. Brooks、Andrew V. Mossine、Melanie S. Sanford、Peter J. H. Scott

  DOI：10.1021/acs.orglett.6b02911

  日期：2016.10.21

  A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [18F]F-phenylalanine and [18F]F-DOPA

  描述了用[ 18 F] KF进行的铜介导的芳基和乙烯基锡烷的亲核放射性氟化反应。该方法快速，使用可商购的试剂，并且与富电子和缺电子的芳烃底物兼容。该方法已应用于人工合成各种临床相关的放射性示踪剂，包括受保护的[ 18 F] F-苯丙氨酸和[ 18 F] F-DOPA。另外，已证明[ 18 F] MPPF的自动合成可提供200±20 mCi的临床验证剂量，并具有2400±900 Ci / mmol的高比活度。
• Tc-labeled arylpiperazine derivatives for imaging serotonin receptor
  申请人：Park Hyun Sang

  公开号：US20070036715A1

  公开（公告）日：2007-02-15

  The present invention relates to Tc-labeled arylpiperazine derivatives for imaging serotonin receptor and, more particularly, to arylpiperazine derivatives coupled with MAMA-disulfide, N 2 S 2 or dimethyl-N 2 S 2 chelating ligand represented by the following chemical formula (1). New arylpiperazine derivatives according to the present invention have no problem of amide hydrolysis in metabolism and have a high affinity for serotonin receptors, and can be labeled with an optimum radionuclide of technetium, thereby being usefully applied for monitoring neurodegenerative diseases or neurological diseases of a mammal.

  本发明涉及用于成像5-羟色胺受体的Tc标记的芳基哌嗪衍生物，更具体地说，涉及与MAMA-二硫化物、N2S2或二甲基-N2S2螯合配体偶联的芳基哌嗪衍生物，其化学式如下（1）。根据本发明的新芳基哌嗪衍生物在代谢中没有酰胺水解问题，对5-羟色胺受体具有高亲和力，并且可以与锝的最佳放射性核素标记，因此可以用于监测哺乳动物的神经退行性疾病或神经系统疾病，具有实用价值。
• Highly Efficient Synthesis and Imaging Studies of an Arylpiperazine Derivative as a 5-HT_1AReceptor Imaging Agent
  作者：Sang Hyun Park、Hui Jeong Gwon、Seung Ho Jang、Hyosun Lee

  DOI：10.1246/cl.2006.1304

  日期：2006.11

  A novel and straightforward microwave synthesis of a new arylpiperazine derivative 3 which has an N2S2 moiety has been developed and radiolabeled with an optimum radionuclide of technetium in the presence of a borohydride exchange resin (BER) as a reducing agent. According to the present study this new radiolabeled compound 4 could have the potential for a diagnostic application as an imaging agent of a serotonin neuroreceptor.

  已开发出一种新颖且直接的微波合成方法，用于制备一种具有N2S2结构的新型芳基哌嗪衍生物3，并使用硼氢化物交换树脂（BER）作为还原剂，在其存在下与锝的最佳放射性核素进行标记。根据本研究，这种新型的放射性标记化合物4有可能作为血清素神经受体的成像剂，用于诊断应用。
• EFFICIENT SYNTHETIC METHOD OF 18F-MEFWAY PRECURSOR
  申请人：RYU Young Hoon

  公开号：US20120136152A1

  公开（公告）日：2012-05-31

  The present invention relates a novel method for preparing an 18 F-mefway precursor. The present invention provides an efficient synthetic method of an 18 F-mefway precursor, which comprises an improved the acid chloride coupling reaction and proper reduction condition to suppress breakdown of amide bond and can obtain the precursor in high yield.

  本发明涉及一种制备18F-mefway前体的新方法。本发明提供了一种高效的合成方法，包括改进的酸氯化物偶联反应和适当的还原条件，以抑制酰胺键的降解，并可以高产率地获得前体。
• Structural Insights into 5-HT_1A/D₄ Selectivity of WAY-100635 Analogues: Molecular Modeling, Synthesis, and in Vitro Binding
  作者：Sébastien Dilly、Jean-François Liégeois

  DOI：10.1021/acs.jcim.5b00753

  日期：2016.7.25

  WAY-100635 and analogues from a structural point of view. In silico investigations revealed two key interactions for the 5-HT1A/D4 selectivity of WAY-100635 and analogues. First, a hydrogen bond only found with the Ser 7.36 of D4 receptor appeared to be the key for a higher D4 affinity for newly synthesized aza analogues. The role of Ser 7.36 was confirmed as the affinity of aza analogues for the mutant

  对5-HT 1A受体作为治疗靶点的兴趣的兴起需要存在高度选择性的5-HT 1A配体。迄今为止，WAY-100635已成为这些受体的原型拮抗剂。然而，该化合物对D 4多巴胺受体也具有显着的亲和力和活性。在这种情况下，这项工作旨在从结构的角度更好地理解WAY-100635及其类似物的5-HT 1A / D 4选择性。在计算机分析中，揭示了WAY-100635和类似物对5-HT 1A / D 4选择性的两个关键相互作用。首先，仅在D 4的Ser 7.36中发现氢键受体似乎是对新合成的氮杂类似物具有更高的D 4亲和力的关键。证实了Ser 7.36的作用，因为氮杂类似物对突变体D 4受体S7.36A的亲和力降低了。然后，与保守的Ser 5.42残基形成另一个氢键似乎对D 4结合也很关键。