(1RS,2RS,4SR)-4-(4-fluorobenzyloxy)-2-(4-phenyl-piperidin-1-yl)-cyclohexanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1RS,2RS,4SR)-4-(4-fluorobenzyloxy)-2-(4-phenyl-piperidin-1-yl)-cyclohexanol
• 英文别名: 4-O-fluorobenzyl ether vesamicol；(1R,2R,4S)-4-(4-fluorobenzyloxy)-2-(4-phenylpiperidin-1-yl)cyclohexanol；(1R,2R,4S)-4-[(4-fluorophenyl)methoxy]-2-(4-phenylpiperidin-1-yl)cyclohexan-1-ol
• 化学式: C₂₄H₃₀FNO₂
• 分子量: 383.506
• InChiKey: AZVJXFKMLABOQL-RBZQAINGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-环氧环己醇 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (1RS,2RS,4SR)-4-(4-fluorobenzyloxy)-2-(4-phenyl-piperidin-1-yl)-cyclohexanol
  参考文献：
  名称：

  vesamicol的新型4和5取代苄基醚衍生物的合成及其与囊泡乙酰胆碱转运蛋白位点的结合特性的体外评估。

  摘要：

  中央胆碱能缺陷的检测是阿尔茨海默氏病的一贯特征，对于在疾病的非常早期就已经采取预防措施和/或对症治疗是必不可少的。囊泡乙酰胆碱转运蛋白（VAChT）代表建立PET放射性示踪剂的适当目标，该PET示踪剂足以使大脑对胆碱能末端的丧失进行成像。在这里，我们描述了维他命克新衍生物的合成和结合特性，该衍生物已知代表VAChT位点的特异性拮抗剂。通过相同环氧化物前体的不同区域选择性开环反应，已经合成了在环己基环上被4-或5-取代的维他命醇的新型苄基醚衍生物。通过使用radio标记的放射性配体在大鼠脑和肝膜制剂中进行的竞争性放射性配体结合研究，分析了新化合物对VAChT位点的亲和力和选择性。vesamicol 10b的4-取代氟苄基醚显示出对VAChT位点的高亲和力（K（i）-值（10b）= 10.7 +/- 1.7 nM），但还显示了与sigma受体（K（i- ）值（10b）＝ 18.5 +/- 6.9nM，[（3）H]

  DOI：

  10.1016/j.bmc.2003.12.035

文献信息

• New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure
  作者：Claudia Barthel、Dietlind Sorger、Winnie Deuther-Conrad、Matthias Scheunemann、Stephanie Schweiger、Petra Jäckel、Ali Roghani、Jörg Steinbach、Gerrit Schüürmann、Osama Sabri、Peter Brust、Barbara Wenzel

  DOI：10.1016/j.ejmech.2015.05.033

  日期：2015.7

  To verify vesamicol as lead structure in the development of radioligands for imaging of VAChT in the brain by PET, we systematically modified this molecule and investigated four different groups of derivatives. Structural changes were conducted in all three ring systems A, B, and C resulting in a library of different vesamicol analogs. Based on their in vitro binding affinity toward VAChT as well as sigma(1) and sigma(2) receptors, we performed a structure-affinity relationship (SAR) study regarding both affinity and selectivity. The compounds possessed VAChT affinities in the range of 132 nM (benzovesamicol) to >10 mu M and selectivity factors from 0.1 to 73 regarding sigma(1) and sigma(2) receptors, respectively. We could confirm the exceptional position of benzovesamicols as most affine VAChT ligands. However, we also observed that most of the compounds with high VAChT affinity demonstrated considerable affinity in particular to the sigma(1) receptor. Finally, none of the various vesamicol analogs in all four groups showed an in vitro binding profile suitable for specific VAChT imaging in the brain. (C) 2015 Elsevier Masson SAS. All rights reserved.