FPNET | 868687-33-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: FPNET
• 英文别名: (2S,3S)-2-[α-(2-(3-fluoropropyl)phenoxy)phenylmethyl]morpholine；(2S)-2-[(S)-[2-(3-fluoropropyl)phenoxy](phenyl)methyl]morpholine；(2S,3S)-2-[alpha-(2-(3-Fluoropropyl)phenoxy)phenylmethyl]morpholine；(2S)-2-[(S)-[2-(3-fluoropropyl)phenoxy]-phenylmethyl]morpholine
• CAS: 868687-33-6
• 化学式: C₂₀H₂₄FNO₂
• 分子量: 329.414
• InChiKey: ROTDEDNYANYXDF-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2S,3S)-N-tert-butoxycarbonyl-2-[α-(2-(3-fluoropropyl)phenoxy)phenylmethyl]morpholine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以29 mg的产率得到FPNET
  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

• Substituted morpholine compounds for the treatment of central nervous system disorders
  申请人：Barta S. Nancy

  公开号：US20050245519A1

  公开（公告）日：2005-11-03

  This invention relates to compounds of the formulae I wherein R 1 -R 8 , A, X, and Z are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system disorders.

  这项发明涉及到公式I中的化合物，其中R1-R8，A，X和Z的定义如规范中所述，包含它们的药物组合物以及它们在治疗中枢神经系统疾病中的用途。
• SUBSTITUTED MORPHOLINE COMPOUNDS FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS
  申请人：Warner-Lambert Company LLC

  公开号：EP1745029A1

  公开（公告）日：2007-01-24
• US7659394B2
  申请人：——

  公开号：US7659394B2

  公开（公告）日：2010-02-09
• [EN] SUBSTITUTED MORPHOLINE COMPOUNDS FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS<br/>[FR] COMPOSES DE MORPHOLINE SUBSTITUES PERMETTANT DE TRAITER DES TROUBLES DU SYSTEME NERVEUX CENTRAL
  申请人：WARNER LAMBERT CO

  公开号：WO2005105763A1

  公开（公告）日：2005-11-10

  This invention relates to compounds of the formulae (I), (II), (III), wherein R'- Re, A, X, and Z are defined as in the specification, pharmaceutical compositions containing them and their use in the treatment of central nervous system disorders.
• 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.