1-(4-amino-3-hydroxy-phenyl)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-1-one | 746666-22-8

• 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: 1-(4-amino-3-hydroxy-phenyl)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-1-one
• CAS: 746666-22-8
• 化学式: C₂₁H₂₅FN₂O₂
• 分子量: 356.44
• InChiKey: XYZKTJKCAGXZIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.56
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [¹¹C]phosgene 、 1-(4-amino-3-hydroxy-phenyl)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-1-one 以 二氯甲烷 为溶剂， 反应 0.05h， 生成 6-[3-[4-(4-fluorobenzyl)piperidino]propionyl]-3H-benzoxazol-2-[11C]one
  参考文献：
  名称：

  Radiosynthesis and pharmacological evaluation of [11C]EMD-95885: a high affinity ligand for NR2B-containing NMDA receptors

  摘要：

  EMD-95885, 6-[3-[4-(4-fluorobenzyl)piperidino]propionyl]-3H-benzoxazol-2-one (1) has been described as a selective antagonist for the NMDA receptors containing NR2B subunits, displaying an IC50 of 3.9 nM for this subtype. EMD-95885 (1) has been synthesized in good overall yield and labelled with carbon-11 (T-1/2: 20.4min) at its benzoxazolinone moiety using [C-11]phosgene. The pharmacological profile of [C-11]EMD-95885 ([C-11]-1) was evaluated in vivo in rats with biodistribution studies and brain radioactivity monitored with intracerebral radiosensitive (beta-microprobes. The brain uptake of [C-11]-1 was homogeneous (0.4-0.6% ID/mL) across the different brain structures studied. This in vivo brain regional distribution of [C-11]-1 was not consistent with the known distribution of NR2B subunits. Also as a measure of specificity the hippocampus/cerebellum ratio reached 0.8 throughout the time course of the experiment supporting the lack of specificity. Competition studies with the NR2B prototypic ligand ifenprodil and EMD-95885 (1), 30 min before the radioligand injection, displayed homogeneous reduction of [(11) C]-1 uptake of 40-60%. Pre-treatment of rats with DTG (sigma ligand), MDL105519 (glycine site antagonist) and MK801 (ion channel blocker) had no inhibitory effect on [C-11]-1 uptake. Use of haloperidol as a blocking drug also resulted in a homogeneous inhibition of [C-11]-1 uptake by 66-60%, which does not reflect binding to dopamine or a receptors. Due to the homogeneous radioligand uptake and inhibition and no measure of cerebral blood flow effects during these blocking studies it is uncertain whether any specific binding is observed. In view of these results, [C-11]EMD-95885 ([C-11]-1) does not have the required properties for imaging NR2B containing NMDA receptors using positron emission tomography. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.065
• 作为产物：
  描述：

  6-(3-氯-1-氧代丙基)-2(3h)-苯噁唑酮 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 1-(4-amino-3-hydroxy-phenyl)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-1-one
  参考文献：
  名称：

  Radiosynthesis and pharmacological evaluation of [11C]EMD-95885: a high affinity ligand for NR2B-containing NMDA receptors

  摘要：

  EMD-95885, 6-[3-[4-(4-fluorobenzyl)piperidino]propionyl]-3H-benzoxazol-2-one (1) has been described as a selective antagonist for the NMDA receptors containing NR2B subunits, displaying an IC50 of 3.9 nM for this subtype. EMD-95885 (1) has been synthesized in good overall yield and labelled with carbon-11 (T-1/2: 20.4min) at its benzoxazolinone moiety using [C-11]phosgene. The pharmacological profile of [C-11]EMD-95885 ([C-11]-1) was evaluated in vivo in rats with biodistribution studies and brain radioactivity monitored with intracerebral radiosensitive (beta-microprobes. The brain uptake of [C-11]-1 was homogeneous (0.4-0.6% ID/mL) across the different brain structures studied. This in vivo brain regional distribution of [C-11]-1 was not consistent with the known distribution of NR2B subunits. Also as a measure of specificity the hippocampus/cerebellum ratio reached 0.8 throughout the time course of the experiment supporting the lack of specificity. Competition studies with the NR2B prototypic ligand ifenprodil and EMD-95885 (1), 30 min before the radioligand injection, displayed homogeneous reduction of [(11) C]-1 uptake of 40-60%. Pre-treatment of rats with DTG (sigma ligand), MDL105519 (glycine site antagonist) and MK801 (ion channel blocker) had no inhibitory effect on [C-11]-1 uptake. Use of haloperidol as a blocking drug also resulted in a homogeneous inhibition of [C-11]-1 uptake by 66-60%, which does not reflect binding to dopamine or a receptors. Due to the homogeneous radioligand uptake and inhibition and no measure of cerebral blood flow effects during these blocking studies it is uncertain whether any specific binding is observed. In view of these results, [C-11]EMD-95885 ([C-11]-1) does not have the required properties for imaging NR2B containing NMDA receptors using positron emission tomography. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.065

文献信息

• Roger, G.; Liu, X.; Lagnel, B., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S32 - S32
  作者：Roger, G.、Liu, X.、Lagnel, B.、Besret, L.、Bramoulle, Y.、Coulon, C.、Ottaviani, M.、Valette, H.、Kassiou, M.、Bottlaender, M.、Dolle, F.

  DOI：——

  日期：——