tert-butyl (2S,3S)-2-[α-(2-(2-hydroxypropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate | 1097104-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: tert-butyl (2S,3S)-2-[α-(2-(2-hydroxypropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate
• 英文别名: tert-butyl (2S)-2-[(S)-[2-(3-hydroxypropyl)phenoxy]-phenylmethyl]morpholine-4-carboxylate
• CAS: 1097104-28-3
• 化学式: C₂₅H₃₃NO₅
• 分子量: 427.541
• InChiKey: WZYYEIXOHXFNLK-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,3S)-2-[α-(2-(2-hydroxypropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate 、 对甲苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以55%的产率得到tert-butyl (2S,3S)-2-[α-(2-(2-tosyloxypropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate
  参考文献：
  名称：

  Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 Labeled Reboxetine Analogues: Potential Positron Emission Tomography Radioligands for in Vivo Imaging of the Norepinephrine Transporter

  摘要：

  Reboxetine analogues with methyl and fluoroalkyl substituents at position 2 of the phenoxy ring 1-4 were synthesized. In vitro competition binding with [H-3]nisoxetine demonstrated that 1-4 have a high affinity for the norepinephrine transporter (NET) with K-i's = 1.02, 3.14, 3.68, and 0.30 nM, respectively. MicroPET imaging in rhesus monkeys showed that the relative regional distribution of [C-11]1 and [C-11]4 is consistent with distribution of the NET in the brain, while [F-18]2 and [F-18]3 showed only slight regional differentiation in brain uptake. Especially, the highest ratios of uptake of [C-11]1in NET-rich regions to that in caudate were obtained at 1.30-1.45 at 45 min and remained relatively constant over 85 min. Pretreatment of the monkey with the selective NET inhibitor, desipramine, decreased the specific binding for both ["C]l and [C-11]4. PET imaging in awake monkeys suggested that anesthesia influenced the binding potential of [C-11]1 and [C-11]4 at the NET.

  DOI：

  10.1021/jm800817h
• 作为产物：
  描述：

  tert-butyl (2S,3S)-2-[α-(2-(3-methoxy-3-oxopropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 0.5h， 以70%的产率得到tert-butyl (2S,3S)-2-[α-(2-(2-hydroxypropyl)phenoxy)(phenyl)methyl]morpholine-4-carboxylate
  参考文献：
  名称：

  Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 Labeled Reboxetine Analogues: Potential Positron Emission Tomography Radioligands for in Vivo Imaging of the Norepinephrine Transporter

  摘要：

  Reboxetine analogues with methyl and fluoroalkyl substituents at position 2 of the phenoxy ring 1-4 were synthesized. In vitro competition binding with [H-3]nisoxetine demonstrated that 1-4 have a high affinity for the norepinephrine transporter (NET) with K-i's = 1.02, 3.14, 3.68, and 0.30 nM, respectively. MicroPET imaging in rhesus monkeys showed that the relative regional distribution of [C-11]1 and [C-11]4 is consistent with distribution of the NET in the brain, while [F-18]2 and [F-18]3 showed only slight regional differentiation in brain uptake. Especially, the highest ratios of uptake of [C-11]1in NET-rich regions to that in caudate were obtained at 1.30-1.45 at 45 min and remained relatively constant over 85 min. Pretreatment of the monkey with the selective NET inhibitor, desipramine, decreased the specific binding for both ["C]l and [C-11]4. PET imaging in awake monkeys suggested that anesthesia influenced the binding potential of [C-11]1 and [C-11]4 at the NET.

  DOI：

  10.1021/jm800817h

文献信息

• Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 Labeled Reboxetine Analogues: Potential Positron Emission Tomography Radioligands for in Vivo Imaging of the Norepinephrine Transporter
  作者：Fanxing Zeng、Jiyoung Mun、Nachwa Jarkas、Jeffrey S. Stehouwer、Ronald J. Voll、Gilles D. Tamagnan、Leonard Howell、John R. Votaw、Clinton D. Kilts、Charles B. Nemeroff、Mark M. Goodman

  DOI：10.1021/jm800817h

  日期：2009.1.8

  Reboxetine analogues with methyl and fluoroalkyl substituents at position 2 of the phenoxy ring 1-4 were synthesized. In vitro competition binding with [H-3]nisoxetine demonstrated that 1-4 have a high affinity for the norepinephrine transporter (NET) with K-i's = 1.02, 3.14, 3.68, and 0.30 nM, respectively. MicroPET imaging in rhesus monkeys showed that the relative regional distribution of [C-11]1 and [C-11]4 is consistent with distribution of the NET in the brain, while [F-18]2 and [F-18]3 showed only slight regional differentiation in brain uptake. Especially, the highest ratios of uptake of [C-11]1in NET-rich regions to that in caudate were obtained at 1.30-1.45 at 45 min and remained relatively constant over 85 min. Pretreatment of the monkey with the selective NET inhibitor, desipramine, decreased the specific binding for both ["C]l and [C-11]4. PET imaging in awake monkeys suggested that anesthesia influenced the binding potential of [C-11]1 and [C-11]4 at the NET.