[¹⁸F]T807 | 1522051-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [¹⁸F]T807
• 英文别名: 7-(6-[¹⁸F]fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole；[¹⁸F]flortaucipir；[¹⁸F]AV-1451；AV-1451；Flortaucipir F-18；7-(6-(18F)fluoranylpyridin-3-yl)-5H-pyrido[4,3-b]indole
• CAS: 1522051-90-6
• 化学式: C₁₆H₁₀FN₃
• 分子量: 262.275
• InChiKey: GETAAWDSFUCLBS-SJPDSGJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

初步的小鼠研究表明，母化合物和四种未表征的代谢物之一，称为代谢物1，被假定是[¹⁸F]氟化物。血浆放射性仅对应于母化合物和代谢物1。所有代谢物都在肝脏中检测到，而除了代谢物2之外的所有代谢物都在肾脏中找到。

Initial studies in mice described the parent compound and four uncharacterized metabolites, one of which, termed metabolite 1, is presumed to be [¹⁸F]fluoride. Plasma radioactivity corresponded only to the parent compound and metabolite 1. All metabolites were detected in the liver while all metabolites except metabolite 2 were found in the kidneys.

来源:DrugBank

毒理性

• 毒性总结

关于Flortaucipir F-18的毒性信息并不容易获得。经历药物过量的患者有出现严重不良反应的风险，如头痛和血压升高。建议采取对症和支持性措施。

Toxicity information regarding Flortaucipir F-18 is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as headaches and increased blood pressure. Symptomatic and supportive measures are recommended.

来源:DrugBank

吸收、分配和排泄

• 吸收

氟罗他昔匹 F-18 通过静脉弹丸注射给药，小鼠在大约2分钟内达到4.16% ID/g的峰值脑摄取。人类研究证实了从外周循环到大脑的快速转移，这些研究显示在给药后大约5分钟，受试者灰质中的峰值SUV大于2。人类的药代动力学研究表明，在大约55分钟（洛根DVR）和80至100分钟（SUVR）达到平衡，当前指南建议在初次给药后大约80分钟开始成像。

Flortaucipir F-18 is administered as an intravenous bolus injection, and peak brain uptake in mice of 4.16% ID/g is achieved by 2 minutes. Fast transfer from the peripheral circulation to the brain was corroborated by human studies that demonstrated peak SUV in gray matter >2 across subjects approximately 5 minutes after administration. Pharmacokinetic studies in humans suggest that equilibrium is achieved by 55 minutes (Logan DVR) and by 80 - 100 minutes (SUVR), and current guidelines recommend initiating imaging approximately 80 minutes after initial administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

Flortaucipir F-18的主要消除途径是通过肾脏。

The major route of elimination for Flortaucipir F-18 is via the kidneys.

来源:DrugBank

吸收、分配和排泄

• 分布容积

18F-Flortaucipir注射到小鼠体内后，主要在肾脏积累（注射后5分钟为14.99 ± 0.39 %ID/g，30分钟为5.52 ± 0.91 %ID/g）和肝脏（5分钟/30分钟分别为4.44 ± 0.16/5.99 ± 0.42 %ID/g）。它能够穿越血脑屏障，早期渗透相对较高（注射后5分钟为4.43 ± 0.91 %ID/g），后期残留渗透较低（30分钟为0.62 ± 0.06 %ID/g）。在全身循环中以及肌肉和骨骼中都能检测到18F-Flortaucipir的量。

Flortaucipir F-18 injected into mice accumulates primarily in the kidneys (14.99 ± 0.39 %ID/g at five minutes and 5.52 ± 0.91 %ID/g at 30 minutes post-injection) and liver (4.44 ± 0.16/5.99 ± 0.42 %ID/g at five/30 minutes, respectively). It is able to cross the blood-brain barrier, with relatively high penetration early (4.43 ± 0.91 %ID/g at five minutes) and low residual penetration later (0.62 ± 0.06 %ID/g at 30 minutes). Detectable amounts of Flortaucipir F-18 are found in the systemic circulation, as well as in muscle and bone.

来源:DrugBank

反应信息

• 作为产物：
  描述：

  3-溴-4-硝基吡啶 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 Kryptofix222[18F]钾盐 、 sodium carbonate 、 caesium carbonate 、 亚磷酸三乙酯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 55.25h， 生成 [¹⁸F]T807
  参考文献：
  名称：

  全自动合成[ 18 F] T807，一种用于阿尔茨海默氏病的PET tau示踪剂

  摘要：

  由（4-溴苯基）硼酸，3-溴-4-硝基吡啶和3-溴-6-硝基吡啶合成正构标准品T807及其硝基前体T807P以及受t -Boc保护的T807P放射性标记前体，三步法的化学收率分别为27％，三到五步的化学收率为4–7％，四到五步的化学收率为3–8％。[ 18 F] T807是由T807P通过K [ 18 F] F / Kryptofix 2.2.2在DMSO中于140°C的亲核性[ 18 F]氟化反应合成的，然后通过5-10手动合成铁粉/ HCOOH还原衰减百分率可分两步校正放射化学产率。[ 18 F] T807也由t -Boc保护的T807P通过同时[ 18在DMSO中于140°C下用K [ 18 F] F / Kryptofix 2.2.2对F]进行氟化和脱保护，并在自行构建的自动[ 18 F]放射合成模块中通过HPLC-SPE方法进行纯化，并使用20–30％衰减校正的放射化学一步即可完成。轰击（EOB）结束时[

  DOI：

  10.1016/j.bmcl.2015.05.035

文献信息

• [EN] METHODS AND COMPOUNDS USING IN-LOOP FLUORINATION<br/>[FR] PROCÉDÉS ET COMPOSÉS FAISANT APPEL À UNE FLUORATION EN BOUCLE
  申请人：CAMH

  公开号：WO2020222041A1

  公开（公告）日：2020-11-05

  This invention provides a novel method that is simple, efficient, and allows for a reliable production of fluorine- 18 (18F) radiofluorinated compounds and radiopharmaceuticals. The method comprises an "in-loop" process, where an 18F source is reacted with a precursor compound in an injection loop of a high-performance liquid chromatography (HPLC) system to form a radiolabeling reagent. The [18F]triflyl fluoride, the radiolabeling agent, is reacted with 1,4-dinitrobenzene to form [18F] l-fluoro-4-nitrobenzene, which was then reacted with compounds of interest. The invention provides 18F radiolabeled compounds in high radiochemical yield. The resulting compounds have use as radiotracers and PET imaging agents. The method can also be used to produce 19F compounds.

  这项发明提供了一种新颖的方法，该方法简单、高效，并且能够可靠地生产氟-18（18F）放射性氟化化合物和放射性药物。该方法包括一个“循环中”过程，其中将18F源与高绩效液相色谱（HPLC）系统的注射环中的前体化合物反应，形成放射性标记试剂。放射性标记剂[18F]三氟甲磺酸与1,4-二硝基苯反应，形成[18F] l-氟-4-硝基苯，然后与感兴趣的化合物反应。该发明提供了高放射性化学产率的18F放射性标记化合物。所得化合物可用作放射性示踪剂和PET成像剂。该方法也可用于生产19F化合物。
• [EN] COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES<br/>[FR] COMPOSÉS POUR L'IMAGERIE D'AGRÉGATS DE PROTÉINES TAU.
  申请人：AC IMMUNE SA

  公开号：WO2018015549A1

  公开（公告）日：2018-01-25

  The present invention relates to novel compounds of the formula (II) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.

  本发明涉及一种新型化合物，其化学式为(II)，可用于选择性Tau蛋白检测与Tau聚集相关的疾病和异常，如阿尔茨海默病和其他Tau蛋白病变，利用正电子发射断层扫描（PET）成像。
• [EN] COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES<br/>[FR] COMPOSÉS POUR L'IMAGERIE D'AGRÉGATS DE PROTÉINES TAU
  申请人：AC IMMUNE SA

  公开号：WO2018015546A1

  公开（公告）日：2018-01-25

  The present invention relates to novel compounds of the formula (I) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.

  本发明涉及一种可以应用于选择性Tau检测的新化合物（I）的公式，用于使用正电子发射断层扫描（PET）成像检测与Tau聚集相关的疾病和异常，如阿尔茨海默病和其他Tau病理学。
• System, Device and Method for Preparing Tracers and Transferring Materials During Radiosynthesis
  申请人：Gangadharmath Umesh B.

  公开号：US20120283490A1

  公开（公告）日：2012-11-08

  A system, apparatus, and method for transferring chemical solutions and synthesizing a tracer. For transferring chemical solutions, the system comprises a primary container; a secondary container; a first line in communication with the primary container and the secondary container. The first line facilitates the flow of gas and/or liquid between the primary container and the secondary container. A valve located upstream of the secondary container and downstream of the primary container regulates flow within the first line; a second line in communication with the secondary container. For synthesizing a tracer, the system includes a source of a solution having a radionuclide. A first container has a tracer precursor and is in communication with the source of solution.

  一种用于转移化学溶液和合成示踪剂的系统、装置和方法。用于转移化学溶液的系统包括一个主容器；一个次级容器；与主容器和次级容器通信的第一管道。第一管道促进气体和/或液体在主容器和次级容器之间的流动。位于次级容器上游和主容器下游的阀门调节第一管道内的流动；与次级容器通信的第二管道。用于合成示踪剂，系统包括一个具有放射性核素的溶液源。第一个容器具有示踪剂前体，并与溶液源通信。
• Facile Route to 2-Fluoropyridines via 2-Pyridyltrialkylammonium Salts Prepared from Pyridine <i>N</i>-Oxides and Application to ¹⁸F-Labeling
  作者：Hui Xiong、Adam T. Hoye、Kuo-Hsien Fan、Ximin Li、Jennifer Clemens、Carey L. Horchler、Nathaniel C. Lim、Giorgio Attardo

  DOI：10.1021/acs.orglett.5b01703

  日期：2015.8.7

  Among known precursors for 2-[18F]fluoropyridines, pyridyltrialkylammonium salts have shown excellent reactivity; however, their broader utility has been limited because synthetic methods for their preparation suffer from poor functional group compatibility. In this paper, we demonstrate the regioselective conversion of readily available pyridine N-oxides into 2-pyridyltrialkylammonium salts under mild

  在2- [ 18 F]氟吡啶的已知前体中，吡啶基三烷基铵盐已显示出优异的反应性。然而，它们的广泛用途受到限制，因为用于其制备的合成方法具有差的官能团相容性。在本文中，我们证明了在温和且无金属的条件下，易于获得的吡啶N-氧化物向2-吡啶基三烷基铵盐的区域选择性转化。这些可分离的中间体可作为结构多样的2-氟吡啶（包括与PET成像有关的分子）的有效前体。除了提供访问非放射性类似物，此方法已被成功地应用到18 F-标记中的放射合成[ 18 F] AV-1451（[18 F] T807），目前正在开发用于对tau成像的PET示踪剂。