(6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-[2-(2-[¹⁸F]fluoroethoxy)ethyl]-1H-benzotriazole) | 1118608-65-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• 英文名称: (6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-[2-(2-[¹⁸F]fluoroethoxy)ethyl]-1H-benzotriazole)
• 英文别名: 6-[(S)-(4-chlorophenyl)-(1,2,4-triazol-1-yl)methyl]-1-[2-(2-(18F)fluoranylethoxy)ethyl]benzotriazole
• CAS: 1118608-65-3
• 化学式: C₁₉H₁₈ClFN₆O
• 分子量: 399.845
• InChiKey: LSPKCQOGUZYXHF-LYCNMKHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  70.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(2-[¹⁸F]fluoroethoxy)ethyl 4-methylbenzenesulfonate 、 (S)-6-((4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl)-1H-benzo[d][1,2,3]triazole 在 氢氧化钾 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-[2-(2-[¹⁸F]fluoroethoxy)ethyl]-1H-benzotriazole)
  参考文献：
  名称：

  18F-Labelled vorozole analogues as PET tracer for aromatase

  摘要：

  为6-[(S)-(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1-(2-[18F]氟乙基)-1H-苯并三唑,[18F]FVOZ,1及6-[(S)-(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1-[2-(2-[18F]氟乙氧基)乙基]-1H-苯并三唑,[18F]FVOO,2开发了一步及两步的18F标记合成.在两步合成中,采用(S)-6-[(4-氯苯基)-(1H-1,2,4-三唑-1-基)甲基]-1H-苯并三唑(VOZ)与18F标记的乙烷-1,2-二基双(4-甲基苯磺酸酯)或氧二亚乙基-2,1-二基双(4-甲基苯磺酸酯)反应来完成亲核氟化步骤.110~120 min的合成,其放射化学产率分别为9~13%,比活度分别为175±7GBq/μmol和56GBq/μmol(化合物1和2).在一步合成中,采用2-{6-[(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1H-1,2,3-苯并三唑-1-基}乙基4-甲基苯磺酸酯(7)或1-[2-(2-溴乙氧基)乙基]-6-[(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1H-苯并三唑(8)通过18F亲核取代直接进行标记得到相应的示踪剂.标记化合物75min合成后的放射化学产率为36~99%,比活度分别为100GBq/μmol(化合物1)和80GBq/μmol(化合物2).大鼠脑冷冻切片体外放射自显影示踪示特异性结合于内侧杏仁核,终纹床核及视前区,所有这些结果均与11C-标记伏氯唑的结果相符.

  DOI：

  10.1002/jlcr.1502

文献信息

• 18F-Labelled vorozole analogues as PET tracer for aromatase
  作者：Maria Erlandsson、Farhad Karimi、Kayo Takahashi、Bengt Långström

  DOI：10.1002/jlcr.1502

  日期：2008.4

  One- and two-step syntheses for the 18F-labelling of 6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-(2-[18F]fluoroethyl)-1H-benzotriazole, [18F]FVOZ, 1 and 6-[(S)-(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-[2-(2-[18F]fluoroethoxy)ethyl]-1H-benzotriazole, [18F]FVOO, 2 were developed. In the two-step synthesis, the nucleophilic fluorination step was performed by reacting (S)-6-[(4-chlorophenyl)-(1H-1,2,4-triazol-1-yl)methyl]-1H-benzotriazole (VOZ) with either the 18F-labelled ethane-1,2-diyl bis(4-methylbenzenesulfonate) or the oxydiethane-2,1-diyl bis(4-methylbenzenesulfonate). The radiochemical yields were in the range of 9–13% after the 110–120 min total syntheses and the specific radioactivities were 175±7 GBq/µmol and 56 GBq/µmol for compounds 1 and 2, respectively. In the one-step synthesis, the precursor 2-6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1H-1,2,3-benzotriazol-1-yl}ethyl 4-methylbenzenesulfonate (7) or 1-[2-(2-bromoethoxy)ethyl]-6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1H-benzotriazole (8) was directly labelled via an 18F nucleophilic substitution to give the corresponding tracer. The labelled compounds were obtained in 36–99% radiochemical yield after 75-min syntheses. The specific radioactivities are 100 GBq/µmol for compound 1 and 80 GBq/µmol for compound 2. In vitro autoradiography using frozen rat brains illustrated specific binding in the medial amygdala, the bed nucleus of stria terminalis and the preoptic area, all of which corresponded well to the result of 11C-labelled vorozole. Copyright © 2008 John Wiley & Sons, Ltd.

  为6-[(S)-(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1-(2-[18F]氟乙基)-1H-苯并三唑,[18F]FVOZ,1及6-[(S)-(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1-[2-(2-[18F]氟乙氧基)乙基]-1H-苯并三唑,[18F]FVOO,2开发了一步及两步的18F标记合成.在两步合成中,采用(S)-6-[(4-氯苯基)-(1H-1,2,4-三唑-1-基)甲基]-1H-苯并三唑(VOZ)与18F标记的乙烷-1,2-二基双(4-甲基苯磺酸酯)或氧二亚乙基-2,1-二基双(4-甲基苯磺酸酯)反应来完成亲核氟化步骤.110~120 min的合成,其放射化学产率分别为9~13%,比活度分别为175±7GBq/μmol和56GBq/μmol(化合物1和2).在一步合成中,采用2-6-[(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1H-1,2,3-苯并三唑-1-基}乙基4-甲基苯磺酸酯(7)或1-[2-(2-溴乙氧基)乙基]-6-[(4-氯苯基)(1H-1,2,4-三唑-1-基)甲基]-1H-苯并三唑(8)通过18F亲核取代直接进行标记得到相应的示踪剂.标记化合物75min合成后的放射化学产率为36~99%,比活度分别为100GBq/μmol(化合物1)和80GBq/μmol(化合物2).大鼠脑冷冻切片体外放射自显影示踪示特异性结合于内侧杏仁核,终纹床核及视前区,所有这些结果均与11C-标记伏氯唑的结果相符.