N-(5-fluoro-2-phenoxyphenyl)-N-(5-methoxy-2-(2-(tosyloxy)ethyloxy)benzyl)acetamide | 686349-74-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(5-fluoro-2-phenoxyphenyl)-N-(5-methoxy-2-(2-(tosyloxy)ethyloxy)benzyl)acetamide
• 英文别名: N-(5-fluoro-2-phenoxy-phenyl)-N-[2-(2-tosyloxy-ethoxy)-5-methoxybenzyl]-acetamide；N-(5-Fluoro-2-phenoxyphenyl)-N-(5-methoxy-2-(2-tosyloxy-ethoxy)-benzyl)acetamide；N-(5-Fluoro-2-phenoxy-phenyl)-N-[2-(2-tosyloxy-ethoxy)-5-methoxy-benzyl]-acetamide；2-[2-[(N-acetyl-5-fluoro-2-phenoxyanilino)methyl]-4-methoxyphenoxy]ethyl 4-methylbenzenesulfonate
• CAS: 686349-74-6
• 化学式: C₃₁H₃₀FNO₇S
• 分子量: 579.646
• InChiKey: NXXJKNZCEXCLHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(5-fluoro-2-phenoxyphenyl)-N-(5-methoxy-2-(2-(tosyloxy)ethyloxy)benzyl)acetamide 在 tetraethylammonium [18F]fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 ¹⁸F-FEDAA1106
  参考文献：
  名称：

  使用四乙基碳酸氢铵提高 [18F] 氟化物亲核取代反应性和灵活性的有效方法

  摘要：

  用于生成用于 [18F] 放射性标记的反应性 [18F] 氟化物的标准方法是将其捕获在阴离子交换柱上，然后用碱性水溶液将其洗脱，然后进行共沸蒸发以除去水。我们现在开发了一种通过使用四乙基碳酸氢铵的方法，在该方法中我们可以获得 [18F] 氟化物的有效回收率（高达 99%），消除对耗时且低效的共沸蒸发过程的要求，并产生反应性 [18F] 氟化物。 18F] 氟化物可以在合成结束时在有水或无水的情况下进行广泛的脂肪族和芳香族 [18F] 亲核取代，放射化学转化率高达 93%。

  DOI：

  10.1002/ejoc.201402587
• 作为产物：
  描述：

  1,2-双甲苯氧基乙烷 、 N-(5-fluoro-2-phenoxyphenyl)-N-(2-hydroxy-5-methoxybenzyl)acetamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以46%的产率得到N-(5-fluoro-2-phenoxyphenyl)-N-(5-methoxy-2-(2-(tosyloxy)ethyloxy)benzyl)acetamide
  参考文献：
  名称：

  Development of a New Radioligand, N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[¹⁸F]fluoroethyl-5-methoxybenzyl)acetamide, for PET Imaging of Peripheral Benzodiazepine Receptor in Primate Brain

  摘要：

  To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K-i = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 (F-18, beta(+); 96.7%, T-1/2 = 109.8 min). Ligands [F-18]4 and [F-18]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [F-18]fluoromethyl iodide ([F-18]8) and 2-[F-18]fluoroethyl bromide ([F-18]9). The distribution patterns of [F-18]4 and [F-18]5 in mice were consistent with the known distribution of PBR. However, compared with [F-18]5, [F-18]4 displayed a high uptake in the bone of mice. The PET image of [F-18]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [F-18]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [F-18]5 in monkey brain was 1.5 times higher than that of [C-11]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[C-11]methyl,N-(1-methylpropyl)isoquinoline ([C-11]1). Moreover, the in vivo binding of [F-18]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [F-18]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [F-18]4 was rapidly metabolized by defluorination to [F-18]F- in the plasma and brain of mice, whereas [F-18]5 was metabolized by debenzylation to a polar product [F-18]13 only in the plasma. No radioactive metabolite of [F-18]5 was detected in the mouse brain. The biological data indicate that [F-18]5 is a useful PET ligand for PBR and is currently used for imaging PBR in human brain.

  DOI：

  10.1021/jm0304919

文献信息

• Phenyloxyaniline derivatives
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP1894915A1

  公开（公告）日：2008-03-05

  The present invention relates to phenyloxyaniline derivatives, to methods of their production and to uses thereof.

  本发明涉及苯氧基苯胺衍生物、其生产方法及其用途。
• PHENYLOXYANILINE DERIVATIVES
  申请人：LEHMANN Lutz

  公开号：US20110097269A1

  公开（公告）日：2011-04-28

  The present invention relates to phenyloxyaniline derivatives, to methods of their production and to uses thereof.

  本发明涉及苯氧基苯胺衍生物，其生产方法和用途。
• Synthesis and evaluation of fluorine-18 and copper-64 labelled PBR radioligands
  作者：K. C. Probst、D. Izquierdo、J. R. Davies、J. L. E. Bird、T. D. Fryer、H. K. Richards、J. C. Clark、E. A. Warburton、P. L. Weissberg、F. I. Aigbirhio

  DOI：10.1002/jlcr.1274

  日期：2007.4
• US7803960B2
  申请人：——

  公开号：US7803960B2

  公开（公告）日：2010-09-28
• [EN] PHENYLOXYANILINE DERIVATIVES<br/>[FR] DERIVÉS PHÉNYLOXYANILINES
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2008028533A1

  公开（公告）日：2008-03-13

  [EN] The present invention relates to phenyloxyaniline derivatives, to methods of their production and to uses thereof.
  [FR] La présente invention concerne des dérivés phényloxyanilines, leurs procédés de production et leurs utilisations.