[18F]FMDAA1106

• 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: [18F]FMDAA1106
• 英文别名: N-[[2-((18F)fluoranylmethoxy)-5-methoxyphenyl]methyl]-N-(5-fluoro-2-phenoxyphenyl)acetamide
• 化学式: C₂₃H₂₁F₂NO₄
• 分子量: 412.422
• InChiKey: HNCYVWMTXRPXGY-MIGPCILRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(5-Fluoro-2-phenoxy-phenyl)-N-(2-iodomethoxy-5-methoxy-benzyl)-acetamide 在 potassium [¹⁸F]fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [18F]FMDAA1106
  参考文献：
  名称：

  Development of a New Radioligand, N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[¹⁸F]fluoroethyl-5-methoxybenzyl)acetamide, for PET Imaging of Peripheral Benzodiazepine Receptor in Primate Brain

  摘要：

  To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K-i = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 (F-18, beta(+); 96.7%, T-1/2 = 109.8 min). Ligands [F-18]4 and [F-18]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [F-18]fluoromethyl iodide ([F-18]8) and 2-[F-18]fluoroethyl bromide ([F-18]9). The distribution patterns of [F-18]4 and [F-18]5 in mice were consistent with the known distribution of PBR. However, compared with [F-18]5, [F-18]4 displayed a high uptake in the bone of mice. The PET image of [F-18]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [F-18]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [F-18]5 in monkey brain was 1.5 times higher than that of [C-11]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[C-11]methyl,N-(1-methylpropyl)isoquinoline ([C-11]1). Moreover, the in vivo binding of [F-18]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [F-18]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [F-18]4 was rapidly metabolized by defluorination to [F-18]F- in the plasma and brain of mice, whereas [F-18]5 was metabolized by debenzylation to a polar product [F-18]13 only in the plasma. No radioactive metabolite of [F-18]5 was detected in the mouse brain. The biological data indicate that [F-18]5 is a useful PET ligand for PBR and is currently used for imaging PBR in human brain.

  DOI：

  10.1021/jm0304919

文献信息

• Phenyloxyaniline derivatives
  申请人：Lehmann Lutz

  公开号：US20080177108A1

  公开（公告）日：2008-07-24

  The present invention relates to phenyloxyaniline derivatives, to methods of their production and to uses thereof.

  本发明涉及苯氧基苯胺衍生物，其生产方法和用途。
• [18F]FMDAA1106 and [18F]FEDAA1106: two positron-Emitter labeled ligands for peripheral benzodiazepine receptor (PBR)
  作者：Ming-Rong Zhang、Jun Maeda、Kenji Furutsuka、Yuichiro Yoshida、Masanao Ogawa、Tetsuya Suhara、Kazutoshi Suzuki

  DOI：10.1016/s0960-894x(02)00886-7

  日期：2003.1

  We synthesized and evaluated N-(5-fluoro-2-phenoxyphenyl)-N-(2-[F-18]fluoromethyl-5-methoxybenzyl)acetamide ([F-18]FMDAA1106) and N-(5-fluoro-2-phenoxyphenyl)-N-(2-[F-18]fluoroethyl-5-methoxybenzyl)acetamide ([F-18]FEDAA1106) as two potent radioligands for peripheral benzodiazepine receptors (PBR). [F-18]FMDAA1106 and [F-18]FEDAA1106 were respectively synthesized by fluoroalkylation of the desmethyl precursor DAA1123 with [F-18]FCH2I and [F-18]FCH2CH2Br. Ex vivo autoradiograms of [F-18]FMDAA1106 and [F-18]FEDAA1106 binding sites in the rat brains revealed that a high radioactivity was present in the olfactory bulb, the highest PBR density region in the brain. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Zhang, M.-R.; Maeda, J.; Ogawa, M., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S338 - S338
  作者：Zhang, M.-R.、Maeda, J.、Ogawa, M.、Yoshida, Y.、Furutsuka, K.、Kida, T.、Noguchi, J.、Okauchi, T.、Suhara, T.、Suzuki, K.

  DOI：——

  日期：——
• Development of a New Radioligand, <i>N</i>-(5-Fluoro-2-phenoxyphenyl)-<i>N</i>-(2-[¹⁸F]fluoroethyl-5-methoxybenzyl)acetamide, for PET Imaging of Peripheral Benzodiazepine Receptor in Primate Brain
  作者：Ming-Rong Zhang、Jun Maeda、Masanao Ogawa、Junko Noguchi、Takehito Ito、Yuichiro Yoshida、Takashi Okauchi、Shigeru Obayashi、Tetsuya Suhara、Kazutoshi Suzuki

  DOI：10.1021/jm0304919

  日期：2004.4.1

  To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K-i = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 (F-18, beta(+); 96.7%, T-1/2 = 109.8 min). Ligands [F-18]4 and [F-18]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [F-18]fluoromethyl iodide ([F-18]8) and 2-[F-18]fluoroethyl bromide ([F-18]9). The distribution patterns of [F-18]4 and [F-18]5 in mice were consistent with the known distribution of PBR. However, compared with [F-18]5, [F-18]4 displayed a high uptake in the bone of mice. The PET image of [F-18]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [F-18]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [F-18]5 in monkey brain was 1.5 times higher than that of [C-11]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[C-11]methyl,N-(1-methylpropyl)isoquinoline ([C-11]1). Moreover, the in vivo binding of [F-18]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [F-18]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [F-18]4 was rapidly metabolized by defluorination to [F-18]F- in the plasma and brain of mice, whereas [F-18]5 was metabolized by debenzylation to a polar product [F-18]13 only in the plasma. No radioactive metabolite of [F-18]5 was detected in the mouse brain. The biological data indicate that [F-18]5 is a useful PET ligand for PBR and is currently used for imaging PBR in human brain.