(3R,5R)-5-(3-[18F]Fluoromethoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one | 1059188-90-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3R,5R)-5-(3-[18F]Fluoromethoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one
• 英文别名: (3R,5R)-5-[3-((18F)fluoranylmethoxy)phenyl]-3-[[(1R)-1-phenylethyl]amino]-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one
• CAS: 1059188-90-7
• 化学式: C₂₆H₂₄F₄N₂O₂
• 分子量: 471.484
• InChiKey: VIZNNWKKQKFIOX-FPMATVOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (3R,5R)-5-(3-hydroxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidine-2-one 、 [18F]fluoromethyl bromide 在 18-冠醚-6 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 (3R,5R)-5-(3-[18F]Fluoromethoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one
  参考文献：
  名称：

  Synthesis, Ex Vivo Evaluation, and Radiolabeling of Potent 1,5-Diphenylpyrrolidin-2-one Cannabinoid Subtype-1 Receptor Ligands as Candidates for In Vivo Imaging

  摘要：

  We have reported that [methyl-C-11] (3R,5R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([C-11]8, [C-11]MePPEP) binds with high selectivity to cannabinoid type-l (CB1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely, the 4-fluorophenyl (16, FMePPEP), 3-fluoromethoxy (20, FMPEP), 3-fluoromethoxy-d(2) (21, FMPEP-d(2)), and 3-fluoroethoxy analogues (22, FEPEP), and report their activity in an ex vivo model designed to identify compounds suitable for use as positron emission tomography (PET) ligands. These ligands exhibited high, selective potency at CB I receptors in vitro (K-b < 1 nM). Each ligand (30 mu g/kg, iv) was injected into rats under baseline and pretreatment conditions (3, rimonabant, 10 mg/kg, iv) and quantified at later times in frontal cortex ex vivo with liquid chromatography-mass spectrometry (LC-MS) detection. Maximal ligand uptakes were high (22.6-48.0 ng/g). Under pretreatment, maximal brain uptakes were greatly reduced (6.5 - 17.3 ng/g). Since each ligand readily entered brain and bound with high selectivity to CB 1 receptors, we then established and here describe methods for producing [C-11]8, [C-11] 16, and [[F-18]20-22 in adequate activities for evaluation as candidate PET radioligands in vivo.

  DOI：

  10.1021/jm800416m

文献信息

• A one-pot radiosynthesis of [18F]FMPEP-d2 for imaging the cannabinoid receptor 1
  作者：Anna Pees、Neil Vasdev

  DOI：10.1016/j.jfluchem.2023.110194

  日期：2023.11

  (3R,5R)-5-(3-([18F]fluoromethoxy-d2)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([18F]FMPEP-d2) is a promising positron emission tomography (PET) radiopharmaceutical for the imaging of cannabinoid type 1 receptors in human studies. To facilitate widespread use of [18F]FMPEP-d2 we herein report a simplified one-pot synthesis procedure that is broadly applicable

  (3 R ,5 R )-5-(3-([ 18 F]氟甲氧基-d 2 )苯基)-3-((( R )-1-苯乙基)氨基)-1-(4-(三氟甲基)苯基)pyrrolidin-2-one ([ 18 F]FMPEP- d 2 ) 是一种很有前途的正电子发射断层扫描 (PET) 放射性药物，用于人体研究中大麻素 1 型受体的成像。为了促进[ 18 F]FMPEP- d 2的广泛使用，我们在此报告了一种简化的一锅合成程序，该程序广泛适用于酚的18 F-氟甲基化，并且可以使用商业放射性氟化模块（GE TRACERlab）应用于常规临床生产FX2 N）。本方法克服了之前在[ 18 F]FMPEP- d 2合成中的挑战，涉及通过使用二甲苯磺基甲烷- d 2并直接与(3 R ,5 R )-5反应来中间纯化[ 18 F]氟甲基结构单元。 -(3-羟基苯基)-3-[( R )-1-苯乙基氨基]-1-(4-三氟甲基苯基)吡咯烷-2-酮与[