[¹⁸F]fluoro-d₂-methylharmol

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: [¹⁸F]fluoro-d₂-methylharmol
• 英文别名: 7-[dideuterio(fluoranyl)methoxy]-1-methyl-9H-pyrido[3,4-b]indole
• 化学式: C₁₃H₁₁FN₂O
• 分子量: 231.227
• InChiKey: QJFIYKHENLVOAG-CNZSZJTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  肉叶云香碱 在 氢溴酸 、 溶剂黄146 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 24.33h， 生成 [¹⁸F]fluoro-d₂-methylharmol
  参考文献：
  名称：

  Selective binding to monoamine oxidase A: In vitro and in vivo evaluation of 18F-labeled β-carboline derivatives

  摘要：

  In this study we synthesized four different F-18-labeling precursors for the visualization of the monoamino oxidase A using harmol derivatives. Whereas two are for prosthetic group labeling using [F-18]fluoro-d(2)-methyl tosylate and 2-[F-18]fluoroethyl-tosylate, the other three precursors are for direct nucleophilic F-18-labeling. Additionally the corresponding reference compounds were synthesized. The syntheses of [F-18]fluoro-d(2)-methyl-harmol and 2-[F-18] fluoroethyl-harmol were carried out using harmol as starting material. For direct nucleophilic F-18-labeling of the tracers carrying oligoethyled spacers (PEG), a toluenesulfonyl leaving group was employed. The radiolabeling, purification and formulation for each tracer was optimized and evaluated in vitro and in vivo. Stability tests in human serum showed that all tracers were stable over the observation period of 60 min. mu PET studies using of the synthesized tracers revealed that the tracers carrying PEG spacers showed no sufficient brain uptake. Consequently, the F-18-fuoro alkylated tracers [F-18] fluoro-d2-methyl-harmol and 2-[F-18]fluoroethyl-harmol were further evaluated showing SUVs in the brain of 1.0 +/- 0.2 g/mL and 3.4 +/- 0.5 g/mL after 45 min, respectively. In blockade studies the selectivity and specificity of both tracers were demonstrated. However, for [F-18]fluoro-d(2)-methyl-harmol a rapid washout from the brain was also observed. In vitro binding assays revealed that 2-[F-18] fluoroethyl-harmol (IC50 = 0.54 +/- 0.06 nM) has a higher affinity than the F-18-fluoro-d(2)-methylated ligand (IC50 = 12.2 +/- 0.6 nM), making 2-[F-18] fluoroethyl-harmol superior to the other evaluated compounds and a promising tracer for PET imaging of the MAO A. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.040