N-(2-bromo-5-methoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide | 928637-43-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-bromo-5-methoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide
• 英文别名: N-[(2-bromo-5-methoxyphenyl)methyl]-N-(5-fluoro-2-phenoxyphenyl)acetamide
• CAS: 928637-43-8
• 化学式: C₂₂H₁₉BrFNO₃
• 分子量: 444.3
• InChiKey: VODCCKUODANVPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-bromo-5-methoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide 在 四(三苯基膦)钯 bis(tri-n-butyl)tin 、 碘 作用下， 以 甲苯 、 二氯甲烷 为溶剂， 反应 93.0h， 以140 mg的产率得到N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide
  参考文献：
  名称：

  N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[¹³¹I]iodo-5-methoxybenzyl)acetamide:  A Potent Iodinated Radioligand for the Peripheral-type Benzodiazepine Receptor in Brain

  摘要：

  To image the peripheral-type benzodiazepine receptor (PBR) in vivo, we previously developed two positron emission tomography (PET) ligands, N-(2-[C-11],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([C-11]1a) and its [F-18]fluoroethyl analogue ([F-18]1b), for the investigation of PBR in the living human brain. This time, using 1a as a leading compound, we designed two novel iodinated analogues, N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (3a) and N-(2,5-dimethoxybenzyl)-N-(5-iodo-2-phenoxyphenyl)acetamide (3b) for the PBR imaging. Ligands 3 were synthesized by the iodination of tributystannyl precursors 10. Radiolabeling for 3 with I-131 was carried out by the reaction of 10 with [I-131]NaI using H2O2 as an oxidizing agent. In vitro competition experiments determined that 3a exhibited both high affinity and selectivity for PBR (IC50: 7.8 nM) vs CBR (> 1 mu M). Biodistribution study in mice determined that [I-131]3a had a high radioactivity level (1.69% dose/g) in the brain, and its distribution pattern in the brain was consistent with the known distribution of PBR in rodents. Ex vivo autoradiography of the rat brain gave visual evidence that [I-131]3a was a potent and specific radioligand for PBR.

  DOI：

  10.1021/jm061127n
• 作为产物：
  描述：

  4-fluoro-2-nitro-1-phenoxybenzene 在 铁粉 、 sodium hydride 、 氯化铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-(2-bromo-5-methoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide
  参考文献：
  名称：

  N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[¹³¹I]iodo-5-methoxybenzyl)acetamide:  A Potent Iodinated Radioligand for the Peripheral-type Benzodiazepine Receptor in Brain

  摘要：

  To image the peripheral-type benzodiazepine receptor (PBR) in vivo, we previously developed two positron emission tomography (PET) ligands, N-(2-[C-11],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([C-11]1a) and its [F-18]fluoroethyl analogue ([F-18]1b), for the investigation of PBR in the living human brain. This time, using 1a as a leading compound, we designed two novel iodinated analogues, N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (3a) and N-(2,5-dimethoxybenzyl)-N-(5-iodo-2-phenoxyphenyl)acetamide (3b) for the PBR imaging. Ligands 3 were synthesized by the iodination of tributystannyl precursors 10. Radiolabeling for 3 with I-131 was carried out by the reaction of 10 with [I-131]NaI using H2O2 as an oxidizing agent. In vitro competition experiments determined that 3a exhibited both high affinity and selectivity for PBR (IC50: 7.8 nM) vs CBR (> 1 mu M). Biodistribution study in mice determined that [I-131]3a had a high radioactivity level (1.69% dose/g) in the brain, and its distribution pattern in the brain was consistent with the known distribution of PBR in rodents. Ex vivo autoradiography of the rat brain gave visual evidence that [I-131]3a was a potent and specific radioligand for PBR.

  DOI：

  10.1021/jm061127n

文献信息

• AGENTS FOR THERAPY EFFICACY MONITORING AND DEEP TISSUE IMAGING
  申请人：Bornhop J. Darryl

  公开号：US20080031823A1

  公开（公告）日：2008-02-07

  Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents.

  与近红外分子成像、体外和体内功能成像、治疗/疗效监测以及癌症和转移活动成像相关的化合物和方法。展示的化合物和方法涉及外周苯二氮平受体成像、代谢成像、细胞呼吸成像、细胞增殖成像作为包含信号剂的靶向剂。
• DAA PERIPHERAL BENZODIAZEPINE RECEPTOR LIGAND FOR CANCER IMAGING AND TREATMENT
  申请人：Bornhop Darryl J.

  公开号：US20100324130A1

  公开（公告）日：2010-12-23

  Peripheral Benzodiazepine Receptor (PBR) is an attractive target for tumor imaging and treatment due to its up-regulation in numerous cancer cell types. DAA1 106 is a selective PBR ligand with high binding affinity. Aspects of the present invention are series of functionalized DAA1 106 analogs, which can be conjugated to a variety of signaling and treatment moieties, and are widely applicable in PBR targeted molecular imaging and drug delivery.

  外周苯二氮平受体（PBR）是肿瘤成像和治疗的有吸引力的靶点，因为它在许多癌细胞类型中上调。DAA1 106是一种具有高结合亲和力的选择性PBR配体。本发明的方面是一系列功能化的DAA1 106类似物，可以与各种信号和治疗基团结合，并广泛应用于PBR靶向的分子成像和药物传递。
• TARGETED, NIR IMAGING AGENTS FOR THERAPY EFFICACY MONITORING, DEEP TISSUE DISEASE DEMARCATION AND DEEP TISSUE IMAGING
  申请人：Bornhop Darryl J.

  公开号：US20100278739A1

  公开（公告）日：2010-11-04

  Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents.
• Targeted, NIR Imaging Agents for Therapy Efficacy Monitoring, Deep Tissue Disease Demarcation and Deep Tissue Imaging
  申请人：Vanderbilt University

  公开号：US20130177502A1

  公开（公告）日：2013-07-11

  Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents.
• US7754884B2
  申请人：——

  公开号：US7754884B2

  公开（公告）日：2010-07-13