2,3,5,6-tetrafluorophenyl 6-(2,3,5,6-tetrafluorophenoxy)nicotinate | 1207955-01-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,5,6-tetrafluorophenyl 6-(2,3,5,6-tetrafluorophenoxy)nicotinate
• 英文别名: (2,3,5,6-Tetrafluorophenyl) 6-(2,3,5,6-tetrafluorophenoxy)pyridine-3-carboxylate
• CAS: 1207955-01-8
• 化学式: C₁₈H₅F₈NO₃
• 分子量: 435.23
• InChiKey: QRXPMFLHFFPBCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  6-氯烟酸 、 2,3,5,6-四氟苯酚 在 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 以79%的产率得到6-chloronicotinic acid 2,3,5,6-tetrafluorophenyl ester
  参考文献：
  名称：

  One Step Radiosynthesis of 6-[¹⁸F]Fluoronicotinic Acid 2,3,5,6-Tetrafluorophenyl Ester ([¹⁸F]F-Py-TFP): A New Prosthetic Group for Efficient Labeling of Biomolecules with Fluorine-18

  摘要：

  The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using prosthetic groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new F-18-labeled prosthetic group based on nicotinic acid tetrafluorophenyl ester. Reaction of [F-18]fluoride at 40 degrees C with the trimethylammonium precursor afforded 6-[F-18]fluoronicotinic acid tetrafluorophenyl ester ([F-18]F-Py-TFP) directly in 60-70% yield. [F-18]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin alpha(v)beta(3) was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with I-125-echistatin. The nonradioactive conjugates were found to possess high binding affinities with calculated K-i values in the low nanomolar range.

  DOI：

  10.1021/jm9015813

文献信息

• [EN] METHOD FOR THE PRODUCTION OF 18F-LABELED ACTIVE ESTERS AND THEIR APPLICATION EXEMPLIFIED BY THE PREPARATION OF A PSMA-SPECIFIC PET-TRACER<br/>[FR] PROCÉDÉ DE PRODUCTION D'ESTERS ACTIFS MARQUÉS AU 18F ET LEUR APPLICATION ILLUSTRÉE PAR LA PRÉPARATION D'UN TRACEUR POUR PET SPÉCIFIQUE DE L'ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE (PSMA)
  申请人：MAX PLANCK GES ZUR FÖRDERUNG DER WISSENSCHAFTEN E V

  公开号：WO2016030329A1

  公开（公告）日：2016-03-03

  Novel efficient, time-saving and reliable radiofluorination procedures for the production of 18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with 18F- are described. The active ester including [18F]F-Py-TFP and [18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

  本文描述了一种高效、省时和可靠的放射性氟化程序，通过将相应的离子前体与18F-的亲核取代反应制备18F标记的活性酯。其中包括通过其中一种方法制备的[18F]F-Py-TFP和[18F]TFB的活性酯，用于制备PSMA特异性PET示踪剂，如[18F]DCFPyL。这些创新方法的关键优势是高效、制备时间短，且易于自动化。通过这些创新方法制备的至少一种PSMA特异性PET示踪剂的药物组合物，对于正电子发射断层扫描（PET）成像特别是前列腺肿瘤成像非常有用。
• Method for the production of 18F-labeled PSMA-specific PET-tracers
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2993171A1

  公开（公告）日：2016-03-09

  Novel efficient, time-saving and reliable radiofluorination procedures for the production of 18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with 18F- are described. The active ester including [18F]F-Py-TFP and [18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

  本文描述了一种高效、省时和可靠的放射性氟化程序，通过将相应的离子前体与18F进行亲核取代，制备18F标记的活性酯。其中包括通过这些方法制备的[18F]F-Py-TFP和[18F]TFB等活性酯，用于制备PSMA特异性PET示踪剂，如[18F]DCFPyL。这些创新方法的关键优势是效率高、制备时间短和易于自动化。含有至少一种通过创新方法制备的PSMA特异性PET示踪剂的制药组合物，对于正电子发射断层扫描（PET）成像特别是前列腺肿瘤成像非常有用。
• Method for the production of 18F-labeled active esters and their application exemplified by the preparation of a PSMA-specific PET-tracer
  申请人：Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.

  公开号：US10112974B2

  公开（公告）日：2018-10-30

  Novel efficient, time-saving and reliable radiofluorination procedures for the production of 18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with 18F− are described. The active ester including [18F]F-Py-TFP and [18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

  本文介绍了通过 18F- 亲核取代相应的鎓前体生产 18F 标记活性酯的高效、省时和可靠的新型放射性氟化程序。其中一种方法生产的活性酯包括[18F]F-Py-TFP 和 [18F]TFB，用于制备 PSMA 特异性 PET 示踪剂，如[18F]DCFPyL。这些发明方法的主要优点是效率高、制备时间短且非常适合自动化。用本发明方法制备的含有至少一种 PSMA 特异性 PET 示踪剂的药物组合物可用于正电子发射断层扫描（PET）成像，特别是前列腺肿瘤成像。
• METHOD FOR THE PRODUCTION OF 18F-LABELED ACTIVE ESTERS AND THEIR APPLICATION EXEMPLIFIED BY THE PREPARATION OF A PSMA-SPECIFIC PET-TRACER
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften

  公开号：EP3183236B1

  公开（公告）日：2022-04-20
• Novel method for the production of 18F-labeled active esters and their application exemplified by the preparation of a PSMA-specific PET-tracer
  申请人：Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.

  公开号：US20170267717A1

  公开（公告）日：2017-09-21

  Novel efficient, time-saving and reliable radiofluorination procedures for the production of 18 F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with 18 F − are described. The active ester including [ 18 F]F-Py-TFP and [ 18 F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [ 18 F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.