4-[18F]fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide | 187671-70-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[18F]fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide
• 英文别名: p-[18F]MPPF；[18F]-p-MPPF；(18)F-4-fluoro-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)benzamide；4-[F-18]fluoro-N-{2-[1-(2-methoxyphenyl)-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide；(18)-F-MPPF；Mppf F-18；4-(18F)fluoranyl-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylbenzamide
• CAS: 187671-70-1
• 化学式: C₂₅H₂₇FN₄O₂
• 分子量: 433.515
• InChiKey: YJZYDPRMWYWYCG-KPVNRNJOSA-N

物化性质

• 密度：
  1.229±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  48.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯-N-吡啶-2-基乙酰胺 在 吡啶 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 亚硝酸特丁酯 、 potassium [¹⁸F]fluoride 、 copper(II) bis(trifluoromethanesulfonate) 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-[18F]fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide
  参考文献：
  名称：

  [ 18 F] KF的铜介导的芳基锡烷的放射性氟化

  摘要：

  描述了用[ 18 F] KF进行的铜介导的芳基和乙烯基锡烷的亲核放射性氟化反应。该方法快速，使用可商购的试剂，并且与富电子和缺电子的芳烃底物兼容。该方法已应用于人工合成各种临床相关的放射性示踪剂，包括受保护的[ 18 F] F-苯丙氨酸和[ 18 F] F-DOPA。另外，已证明[ 18 F] MPPF的自动合成可提供200±20 mCi的临床验证剂量，并具有2400±900 Ci / mmol的高比活度。

  DOI：

  10.1021/acs.orglett.6b02911

文献信息

• Synthesis ofL-[3,3,4,4,S-methyl-2H7]methionine for use as a substrate for the methionine loading test
  作者：Hiroshi Hasegawa、Yoshihiko Shinohara、Kazunori Tagoku、Takao Hashimoto

  DOI：10.1002/jlcr.428

  日期：2001.1

  Optically pure L-[3,3,4,4,S-methyl-2H7]methionine (L-[2H7]-methionine) for use as a substrate for the methionine loading test has been prepared. The racemic [2H7]methionine was prepared from DL-[3,3,4,4-2H4]methionine (DL-[2H4]methionine) by conversion of the S-CH3 group to a C2H3 group. The racemate was resolved by stereospecific hydrolysis of the N-acetylated derivative with acylase. After an intravenous administration of L-[2H7]methionine in a rat, the concentration of L-[2H7]methionine and the metabolites in plasma were determined by GC-MS-SIM. L-[2H4]Homocysteine and L-[2H4]methionine were detected in plasma at 30 min after dosing. These results show that L-[2H7]methionine was converted by de-methylation and subsequent re-methylation to form L-[2H4]methionine. Copyright © 2001 John Wiley & Sons, Ltd.

  已制备光学纯L-[3,3,4,4,S-甲基-2H7]蛋氨酸（L-[2H7]蛋氨酸），作为蛋氨酸负荷测试的底物。该外消旋体[2H7]蛋氨酸是通过将DL-[3,3,4,4-2H4]蛋氨酸（DL-[2H4]蛋氨酸）的S-CH3基团转化为C2H3基团制备的。通过与酰化酶的立体特异性水解，分离了外消旋混合物。在给大鼠静脉注射L-[2H7]蛋氨酸后，通过气相色谱-质谱-选择离子监测（GC-MS-SIM）测定了L-[2H7]蛋氨酸及其代谢物在血浆中的浓度。L-[2H4]同型半胱氨酸和L-[2H4]蛋氨酸在给药后30分钟时在血浆中被检测到。这些结果表明，L-[2H7]蛋氨酸通过去甲基化和随后的再甲基化转化为L-[2H4]蛋氨酸。版权所有 © 2001 John Wiley & Sons, Ltd.
• [¹⁸F]/¹⁹F exchange in fluorine containing compounds for potential use in¹⁸F-labelling strategies
  作者：Elisabeth Blom、Farhad Karimi、Bengt Långström

  DOI：10.1002/jlcr.1670

  日期：2009.9.30

  Exchange of [18F]fluoride with 19F in various organofluorine compounds in concentrations ranging from 0.06 to 56 mM was explored. We aimed to explore whether exchange reactions can be a potential useful labelling strategy, when there are no requirement of high specific radioactivity. Parameters such as solvents, temperature, conventional vs microwave heating, and the degree of fluorine load in some aromatic and alkyl compounds were investigated with regard to radiochemical yield and specific radioactivity. A series of fluorobenzophenones (1–6), 1-(4-fluorophenyl)ethanone (7), various activated and deactivated fluoro benzenes (8–16), N-(pentafluorophenyl)benzamide (17), (pentafluorophenyl)formamide (18), (tridecafluorohexyl)benzene (19) and tetradecafluorohexane (20) were subjected to [18F]/19F exchange. To test this strategy to label biologically active molecules containing fluorine atoms in an aryl group, two analogues of WAY-100635 (21–22), Lapatinib (23), 2,5,6,7,8-pentafluoro-3-methylnaphthoquinone (24) and 1-(2,4-difluorophenyl)-3-(4-fluorophenyl)propan-1-one (25) were investigated. The multi-fluorinated molecules containing an electron-withdrawing group were successfully labelled at room temperature, whereas the monofluorinated, as well as those containing an electron-donating group, required heating for the exchange reaction to take place. Copyright © 2009 John Wiley & Sons, Ltd.

  在浓度范围为0.06至56 mM的各种有机氟化合物中探索了[18F]氟化物与19F的交换。我们的目标是探讨当不需要高特定放射性时，交换反应是否可以成为一种潜在有用的标记策略。我们研究了溶剂、温度、传统加热与微波加热、以及某些芳香和烷基化合物的氟负载程度对放射化学产率和特定放射性的影响。 一系列氟苯酮（1–6）、1-(4-氟苯基)乙酮（7）、各种活化和去活化的氟苯（8–16）、N-(五氟苯基)苯酰胺（17）、(五氟苯基)甲酰胺（18）、(三十四氟十六烷)苯（19）和十四氟十六烷（20）参与了[18F]/19F交换。为了测试这种策略在含有芳基氟原子的生物活性分子中的标记效果，我们研究了WAY-100635的两个类似物（21–22）、拉帕替尼（23）、2,5,6,7,8-五氟-3-甲基萘醌（24）和1-(2,4-二氟苯基)-3-(4-氟苯基)丙酮（25）。含有电子吸引基团的多氟化分子在室温下成功标记，而单氟化分子以及含有电子供给基团的分子则需要加热才能进行交换反应。版权 © 2009 John Wiley & Sons, Ltd.
• Development of a resonant-type microwave reactor and its application to the synthesis of positron emission tomography radiopharmaceuticals
  作者：Hiroyuki Kimura、Yusuke Yagi、Noriyuki Ohneda、Hiro Odajima、Masahiro Ono、Hideo Saji

  DOI：10.1002/jlcr.3232

  日期：2014.10

  Microwave technology has been successfully applied to enhance the effectiveness of radiolabeling reactions. The use of a microwave as a source of heat energy can allow chemical reactions to proceed over much shorter reaction times and in higher yields than they would do under conventional thermal conditions. A microwave reactor developed by Resonance Instrument Inc. (Model 520/521) and CEM (PETWave) has been used exclusively for the synthesis of radiolabeled agents for positron emission tomography by numerous groups throughout the world. In this study, we have developed a novel resonant-type microwave reactor powered by a solid-state device and confirmed that this system can focus microwave power on a small amount of reaction solution. Furthermore, we have demonstrated the rapid and facile radiosynthesis of 16α-[18F]fluoroestradiol, 4-[18F]fluoro-N-[2-(1-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinylbenzamide, and N-succinimidyl 4-[18F]fluorobenzoate using our newly developed microwave reactor.

  微波技术已成功应用于增强放射性标记反应的有效性。与传统热条件下相比，使用微波作为热能源可以使化学反应在更短的反应时间内进行，并且产率更高。由 Resonance Instrument Inc.（型号 520/521）和 CEM (PETWave) 开发的微波反应器已被世界各地的众多团体专门用于合成用于正电子发射断层扫描的放射性标记试剂。在这项研究中，我们开发了一种由固态装置供电的新型谐振型微波反应器，并证实该系统可以将微波功率集中在少量的反应溶液上。此外，我们还证明了 16α-[18F]氟雌二醇、4-[18F]氟-N-[2-(1-甲氧基苯基)-1-哌嗪基]乙基-N-2-吡啶基苯甲酰胺和 N 的快速、简便的放射合成。 -琥珀酰亚胺基4-[18F]氟苯甲酸酯，使用我们新开发的微波反应器。
• Green approaches to late-stage fluorination: radiosyntheses of ¹⁸F-labelled radiopharmaceuticals in ethanol and water
  作者：Megan N. Stewart、Brian G. Hockley、Peter J. H. Scott

  DOI：10.1039/c5cc05919d

  日期：——

  Green strategies for late-stage fluorination with ¹⁸F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process, have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging.

  已经开发出针对晚期氟化的绿色策略，其中在整个放射标记过程中仅使用乙醇和水作为溶剂，并应用于广泛应用于临床PET成像的一系列放射性药物的放射性合成中。
• Marmoset Serotonin 5-HT_1AReceptor Mapping with a Biased Agonist PET Probe¹⁸F-F13714: Comparison with an Antagonist Tracer¹⁸F-MPPF in Awake and Anesthetized States
  作者：Chihiro Yokoyama、Aya Mawatari、Akihiro Kawasaki、Chiho Takeda、Kayo Onoe、Hisashi Doi、Adrian Newman-Tancredi、Luc Zimmer、Hirotaka Onoe

  DOI：10.1093/ijnp/pyw079

  日期：2016.12

  BACKGROUND In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their "active state," but its brain labeling pattern in nonhuman

  背景技术由于缺乏合适的激动剂正电子发射断层摄影探针，已经阻碍了通过5-羟色胺1A受体的正电子发射断层摄影进行体内作图。18F标记的F13714是最近开发的偏向激动剂正电子发射断层显像探针，其优先靶向处于“活动状态”的血清素1A受体亚群，但尚未描述其在非人类灵长类动物中的脑部标记模式。另外，在非人类动物和人类之间PET数据的可翻译性中存在潜在的混淆，是由于麻醉药的使用可能会改变靶标受体的结合特性。方法在一组普通mar猴（n = 4）中使用血清素1A受体偏向激动剂放射性示踪剂18F-F13714进行正电子发射断层扫描。与特征明确的18F标记拮抗剂放射性示踪剂18F-MPPF相比。在意识和异氟烷麻醉条件下对每只动物进行实验。结果通过正电子发射断层显像在mar猴中18F-F13714的结合分布与18F-MPPF显着不同。18F-MPPF在海马和杏仁核中显示出最高的结合力，而18F-F13714在其