(2S,3S)-N-tert-butoxycarbonyl-2-[α-(2-(2-fluoroethyl)phenoxy)phenylmethyl]morpholine | 1097104-06-7

• 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: (2S,3S)-N-tert-butoxycarbonyl-2-[α-(2-(2-fluoroethyl)phenoxy)phenylmethyl]morpholine
• 英文别名: tert-butyl (2S)-2-[(S)-[2-(2-fluoroethyl)phenoxy]-phenylmethyl]morpholine-4-carboxylate
• CAS: 1097104-06-7
• 化学式: C₂₄H₃₀FNO₄
• 分子量: 415.505
• InChiKey: RTPZAKZXJJCRRK-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-N-tert-butoxycarbonyl-2-[α-(2-(2-fluoroethyl)phenoxy)phenylmethyl]morpholine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以25 mg的产率得到FENET
  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：

  (+)-(2S,3R)-2-[α-hydroxy(phenyl)methyl]morpholine-4-carboxylic acid tert-butyl ester 、 2-(2-fluoroethyl)phenol 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S)-N-tert-butoxycarbonyl-2-[α-(2-(2-fluoroethyl)phenoxy)phenylmethyl]morpholine
  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