2-(2-(2-(4-((4-methoxybenzyl)oxy)phenoxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate

• 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: 2-(2-(2-(4-((4-methoxybenzyl)oxy)phenoxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate
• 英文别名: 2-[2-[2-[4-[(4-Methoxyphenyl)methoxy]phenoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate；2-[2-[2-[4-[(4-methoxyphenyl)methoxy]phenoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate
• 化学式: C₂₇H₃₂O₈S
• 分子量: 516.612
• InChiKey: VTNSUUOORQOONW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(2-(2-(4-((4-methoxybenzyl)oxy)phenoxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 0.08h， 生成 1-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-4-((4-methoxybenzyl)oxy)benzene
  参考文献：
  名称：

  Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography

  摘要：

  A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A beta plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Va118_Phe20 cleft on the flat spine of the A beta fiber, in a manner similar to that of IMPY molecule. The most potent probe, [F-18]9a, exhibited a combination of high binding affinity to A beta aggregates (K-i= 21.0 +/- 4.9 nM), high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain (95% of intact form at 2 min). [F-18]9a clearly labeled A beta plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [F-18]9a did penetrate the intact BBB and specifically bind to A beta plaques in vivo. Overall, [F-18]9a may be a potential PET probe for imaging A beta plaques in AD brains. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.028
• 作为产物：
  描述：

  2-(2-(2-(4-(benzyloxy)phenoxy)ethoxy)ethoxy)ethanol 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 生成 2-(2-(2-(4-((4-methoxybenzyl)oxy)phenoxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography

  摘要：

  A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A beta plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Va118_Phe20 cleft on the flat spine of the A beta fiber, in a manner similar to that of IMPY molecule. The most potent probe, [F-18]9a, exhibited a combination of high binding affinity to A beta aggregates (K-i= 21.0 +/- 4.9 nM), high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain (95% of intact form at 2 min). [F-18]9a clearly labeled A beta plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [F-18]9a did penetrate the intact BBB and specifically bind to A beta plaques in vivo. Overall, [F-18]9a may be a potential PET probe for imaging A beta plaques in AD brains. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.028

文献信息

• PHENYL BENZYL ETHER DERIVATIVE AND PREPARATION METHOD AND APPLICATION THEREOF
  申请人：Beijing Zhibo Bio-Medical Technology Co., Ltd.

  公开号：EP3581565A1

  公开（公告）日：2019-12-18

  The present invention relates to a phenyl benzyl ether derivative, a preparation method thereof and application of the phenyl benzyl ether derivative to the preparation of medicine for diagnosing and treating the Alzheimer's disease (AD), wherein part of compounds, after being labeled by radionuclide, of the phenyl benzyl ether derivative, are used as Aβ plaque imaging agent. The structural formula of the phenyl benzyl ether derivative is shown by formula (I). The present invention develops a kind of brand new phenyl benzyl ether derivative which has high affinity with Aβ plaques in brains of AD patients. The chemical structure of the phenyl benzyl ether derivative is different from that of compounds disclosed in the prior art and the phenyl benzyl ether derivative belongs to a brand new compound for diagnosing and treating AD. The obtained Aβ plaque imaging agent has the advantages that the in-vivo stability is good, the fat solubility is low, the removal speed for the brain is fast, the problem of removing the radionuclide in vivo does not exist, and the application prospect and the market value are great.

  本发明涉及一种苯基苄基醚衍生物及其制备方法，以及该苯基苄基醚衍生物在制备诊断和治疗阿尔茨海默病（AD）药物中的应用，其中苯基苄基醚衍生物的部分化合物经放射性核素标记后用作Aβ斑块成像剂。苯基苄基醚衍生物的结构式如式（I）所示。本发明开发了一种全新的苯基苄基醚衍生物，该衍生物与 AD 患者大脑中的 Aβ 斑块具有高亲和力。该苯基苄基醚衍生物的化学结构不同于现有技术中公开的化合物，属于一种用于诊断和治疗AD的全新化合物。所获得的Aβ斑块成像剂具有体内稳定性好、脂溶性低、脑部清除速度快、不存在放射性核素体内清除问题等优点，应用前景和市场价值巨大。
• Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography
  作者：Yanping Yang、Hualong Fu、Mengchao Cui、Cheng Peng、Zhigang Liang、Jiapei Dai、Zhiyong Zhang、Chunping Lin、Boli Liu

  DOI：10.1016/j.ejmech.2015.09.028

  日期：2015.11

  A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A beta plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Va118_Phe20 cleft on the flat spine of the A beta fiber, in a manner similar to that of IMPY molecule. The most potent probe, [F-18]9a, exhibited a combination of high binding affinity to A beta aggregates (K-i= 21.0 +/- 4.9 nM), high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain (95% of intact form at 2 min). [F-18]9a clearly labeled A beta plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [F-18]9a did penetrate the intact BBB and specifically bind to A beta plaques in vivo. Overall, [F-18]9a may be a potential PET probe for imaging A beta plaques in AD brains. (C) 2015 Elsevier Masson SAS. All rights reserved.