KF4WS22G1C | 2253775-56-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: KF4WS22G1C
• 英文别名: (2R,3R,11bR)-9-(1,1,2,2,3,3-hexadeuterio-3-(18F)fluoranylpropoxy)-10-methoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-ol
• CAS: 2253775-56-1
• 化学式: C₂₁H₃₂FNO₃
• 分子量: 370.442
• InChiKey: GNKGXQHHUUEYQV-JGIPMPBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2R,3R,11bR)-1,3,4,6,7,11b-六氢-10-甲氧基-3-(2-甲基丙基)-2H-苯并[a]喹嗪-2,9-二醇 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.25h， 生成 KF4WS22G1C
  参考文献：
  名称：

  [EN] NOVEL DEUTERIUM SUBSTITUTED POSITRON EMISSION TOMOGRAPHY (PET) IMAGING AGENTS AND THEIR PHARMACOLOGICAL APPLICATION
  [FR] NOUVEAUX AGENTS D'IMAGERIE PAR TOMOGRAPHIE PAR ÉMISSION DE POSITRONS (PET) SUBSTITUÉS PAR DU DEUTÉRIUM ET LEUR APPLICATION PHARMACOLOGIQUE

  摘要：

  本发明涉及根据式I-A、式II-A、式II-D和式III-A的氘代化合物。这些化合物可用作PET成像剂，用于评估帕金森病、阿尔茨海默病，并确定特定的选择性5-羟色胺再摄取抑制剂（SSRIi）活性，用于治疗抑郁症。本发明还涉及包括药用可接受载体和式I-A、式II-A、式II-D或式III-A的化合物，或其药用可接受盐的药物组合物。

  公开号：

  WO2018222549A1

文献信息

• VMAT2 imaging agent, D6-[18F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization
  作者：Ruiyue Zhao、Zhihao Zha、Xinyue Yao、Karl Ploessl、Seok Rye Choi、Futao Liu、Lin Zhu、Hank F. Kung

  DOI：10.1016/j.nucmedbio.2019.07.002

  日期：2019.5

  ([18F]9), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system, was reported as a useful imaging agent for the diagnosis of Parkinson's disease (PD). The production of [18F]9 was optimized and simplified by using solid-phase extraction (SPE) purification. METHODS Three major nonradioactive impurities were synthesized and characterized. The preparation of [18F]9 was optimized

  目标最近，氘化示踪剂，D6- [18F] FP-（+）-DTBZ，9-O-六氘代-3- [18F]氟丙氧基-（+）-二氢丁苯那嗪（[18F] 9），靶向囊泡单胺转运蛋白2据报道中枢神经系统中的VMAT2（VMAT2）是诊断帕金森氏病（PD）的有用成像剂。通过使用固相萃取（SPE）纯化，可以优化和简化[18F] 9的生产。方法合成并表征了三种主要的非放射性杂质。通过使用不同的标记条件优化了[18F] 9的制备，并评估了SPE纯化方法。通过体外结合测定，小鼠体内生物分布测定以及脑切片的离体和体外放射自显影，评估化学杂质对[18F] 9最终剂量的影响。结果发现[18F] 9的最佳氟化条件-在DMSO中于130°C加热10分钟，观察到高放射化学产率和三种主要化学杂质。SPE方法成功地实现了涉及带有两步洗脱过程的Sep-Pak®tC18 Plus发光柱。该过程具有良好的放射化学收率（38.7±10.5％，已校正衰变；放射化学纯度>
• Deuterated 18 F-9-O-hexadeutero-3-fluoropropoxyl-(+)-dihydrotetrabenazine (D6-FP-(+)-DTBZ): A vesicular monoamine transporter 2 (VMAT2) imaging agent
  作者：Futao Liu、Seok Rye Choi、Zhihao Zha、Karl Ploessl、Lin Zhu、Hank F. Kung

  DOI：10.1016/j.nucmedbio.2017.11.009

  日期：2018.2

  Introduction: Vesicular monoamine transporters 2 (VMAT2) in the brain serve as transporter for packaging monoamine in vesicles for normal CNS neurotransmission. Several VMAT2 imaging agents, [C-11]-(+)-DTBZ, dihydrotetrabenazine and [F-18]FP-(+)-DTBZ (9-0-fluoropropyl-(+)-dihydro tetrabenazine, a.k.a. [F-18]AV133), are useful for studying the changes in brain function related to monoamine transmission by in vivo imaging. Deuterated analogs have been reported targeting VMAT2 binding sites.Methods: A novel deuterated [F-18]9-0-hexaduterofluoropropyl-(+)-dihydrotetrabenazine,[18F]D6-FP-(+)DTBZ, [18F]1, was prepared as a VMAT2 imaging agent. This F-18 agent which targeted VMAT2 was evaluated by in vitro binding, in vivo biodistribution and microPET imaging studies in rodents.Results: The one step radiolabeling reaction led to the desired [F-18]D6-FP-(+)-DTBZ, [F-18]1, which showed excellent binding affinity to VMAT2 (Ki = 0.32 +/- 0.07 nM) comparable to that of FP-(+)-DTBZ (Ki = 033 +/- 0.02 nM) using [F-18]FP-(+)-DTBZ and rat striatum membrane homogenates. In vivo biodistribution in normal rats showed that 1, exhibited excellent brain uptake and comparable high ratio of striatum to cerebellum (target/background) ratio at 1 h after injection (ratio of 6.05 +/- 0.43 vs 5.66 +/- 0.72 for [18F]FP-(+)-DTBZ vs [F-18]1, respectively). MicroPET imaging studies in rats further confirm that the striatum with high VMAT2 concentration was clearly delineated in normal rat brain after iv injection of [F-18]1. We observed minor changes of metabolism in rat plasma between these two agents; however, the changes showed little effect on regional brain uptake and retention.Conclusions: The results reported here lend support for using [F-18]D6-FP-(+)-DTBZ, [F-18]1, as in vivo PET imaging agent for VMAT2 binding in the brain. (C) 2017 Elsevier Inc. All rights reserved.