2-溴-N-(2,5-二甲氧基苄基)-N-(2-苯氧基苯基)乙酰胺 | 1104493-09-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-溴-N-(2,5-二甲氧基苄基)-N-(2-苯氧基苯基)乙酰胺
• 英文名称: N-bromoacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
• 英文别名: 2-bromo-N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)acetamide；Br-PBR06；N-(2,5-dimethoxybenzyl)-2-bromo-N-(2-phenoxyphenyl)acetamide；2-bromo-N-[(2,5-dimethoxyphenyl)methyl]-N-(2-phenoxyphenyl)acetamide
• CAS: 1104493-09-5
• 化学式: C₂₃H₂₂BrNO₄
• 分子量: 456.336
• InChiKey: IKVVNTUNSFIAJK-UHFFFAOYSA-N

物化性质

• 熔点：
  72 °C(Solv: ethanol (64-17-5))
• 沸点：
  564.1±50.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-溴-N-(2,5-二甲氧基苄基)-N-(2-苯氧基苯基)乙酰胺 在 18-冠醚-6 、 potassium hydrogencarbonate 、 氢氟酸 作用下， 以 水 、 乙腈 为溶剂， 反应 0.17h， 生成 [¹⁸F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
  参考文献：
  名称：

  Single-Step High-Yield Radiosynthesis and Evaluation of a Sensitive ¹⁸F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET

  摘要：

  Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared, and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new F-18-labeled PBR radioligand, namely [F-18]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([F-18]9). [F-18]9 was produced easily through a single and highly efficient step, the reaction of [F-18]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [F-18]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [F-18]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [F-18]2-fluoro-N-(2-phenoxyphenyl)acetamide ([F-18]11). [F-18]9 is a promising radioligand for future imaging of PBR in living human brain.

  DOI：

  10.1021/jm8011855
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 2-溴-N-(2,5-二甲氧基苄基)-N-(2-苯氧基苯基)乙酰胺
  参考文献：
  名称：

  Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

  摘要：

  The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [F-18]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [C-11]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [C-11]PBR06 was prepared by O-[C-11]methylation of desmethyl-PBR06 with [C-11]CH3OTf in CH3CN at 80 degrees C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/mu mol specific activity at EOB. On the similar grounds, [F-18]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [F-18]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 degrees C with K[F-18]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/mu mol specific activity at EOB. Radiosynthesis of [F-18]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.06.012

文献信息

• J. Med. Chem. 2009, 52, 688-699
  作者：

  DOI：——

  日期：——
• US9458161B1
  申请人：——

  公开号：US9458161B1

  公开（公告）日：2016-10-04
• Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)
  作者：Min Wang、Mingzhang Gao、Kathy D. Miller、Qi-Huang Zheng

  DOI：10.1016/j.steroids.2011.06.012

  日期：2011.11

  The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [F-18]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [C-11]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [C-11]PBR06 was prepared by O-[C-11]methylation of desmethyl-PBR06 with [C-11]CH3OTf in CH3CN at 80 degrees C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/mu mol specific activity at EOB. On the similar grounds, [F-18]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [F-18]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 degrees C with K[F-18]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/mu mol specific activity at EOB. Radiosynthesis of [F-18]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor. (C) 2011 Elsevier Inc. All rights reserved.
• Single-Step High-Yield Radiosynthesis and Evaluation of a Sensitive ¹⁸F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET
  作者：Emmanuelle Briard、Sami S. Zoghbi、Fabrice G. Siméon、Masao Imaizumi、Jonathan P. Gourley、H. Umesha Shetty、Shuiyu Lu、Masahiro Fujita、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm8011855

  日期：2009.2.12

  Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared, and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new F-18-labeled PBR radioligand, namely [F-18]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([F-18]9). [F-18]9 was produced easily through a single and highly efficient step, the reaction of [F-18]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [F-18]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [F-18]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [F-18]2-fluoro-N-(2-phenoxyphenyl)acetamide ([F-18]11). [F-18]9 is a promising radioligand for future imaging of PBR in living human brain.