2,5-dioxopyrrolidin-1-yl 5-oxo-5-((6-(6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl)pyridin-3-yl)amino)pentanoate | 1334209-39-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2,5-dioxopyrrolidin-1-yl 5-oxo-5-((6-(6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl)pyridin-3-yl)amino)pentanoate
• 英文别名: (2,5-dioxopyrrolidin-1-yl) 5-oxo-5-[[6-(6-pyridin-2-yl-1,2,4,5-tetrazin-3-yl)pyridin-3-yl]amino]pentanoate
• CAS: 1334209-39-0
• 化学式: C₂₁H₁₈N₈O₅
• 分子量: 462.425
• InChiKey: AGNDPPCBVFAWHH-UHFFFAOYSA-N

物化性质

• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  170
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl 5-oxo-5-((6-(6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl)pyridin-3-yl)amino)pentanoate 在 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.08h， 生成
  参考文献：
  名称：

  [EN] TETRAZINE-TRANS-CYCLOOCTENE LIGATION FOR THE RAPID CONSTRUCTION OF RADIONUCLIDE LABELED PROBES
  [FR] LIGATURE TÉTRAZINE-TRANS-CYCLOOCTÈNE POUR LA CONSTRUCTION RAPIDE DE SONDES MARQUÉES PAR UN RADIONUCLÉIDE

  摘要：

  公开号：

  WO2012012612A3
• 作为产物：
  描述：

  3-氨基-6-氰基吡啶 在 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 肼 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 2,5-dioxopyrrolidin-1-yl 5-oxo-5-((6-(6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl)pyridin-3-yl)amino)pentanoate
  参考文献：
  名称：

  Synthesis and evaluation of 18F-PTTCO-Cys40-Exendin-4 for PET imaging of ectopic insulinomas in rodents

  摘要：

  A major limitation in the development of radiolabeled Exendin-4 analogues (short half-life isotopes) is an inability to efficiently and rapidly separate final products from precursors. This is important as lack of purity in the final product decreases probe efficiency. The purpose of this study was to develop a method to prepare the highpurity imaging reagent [F-18] PITCO-Cys(40)-Exendin-4. To accomplish this, magnetic TCO-beads were incubated with the crude product to remove unlabeled Exendin-4. In rodents pre-treatment with purified [F-18] PITCO-Cys(40)-Exendin-4 (similar to 1.85 MBq) allowed precise microPET imaging of ectopic insulinomas. Moreover, analogue uptake was successfully blocked by administering non-labelled "cold" Exendin-4. Biodistribution data revealed that [F-18] PITCO-Cys(40)-Exendin-4 accumulated specifically in GLP-1R-enriched insulinomas in mice, confirming results obtained using miroPET. Investigation of [F-18] PITCO-Cys(40)-Exendin-4 as a tracer to image portal vein-transplanted pancreatic islets is proceeding in animals.

  DOI：

  10.1016/j.bioorg.2020.103718

文献信息

• Tetrazine-trans-cyclooctene Ligation for the Rapid Construction of Radionuclide Labeled Probes
  申请人：Fox Joseph M.

  公开号：US20130266512A1

  公开（公告）日：2013-10-10

  A Diels-Alder adduct of a trans-cyclooctene with a tetrazine is provided, wherein the adduct bears a substituent labeled with a radionuclide. A method of producing a PET or other image of an organ in an animal or human includes forming the Diels-Alder adduct in the animal or human. Trans-cyclooctenes and tetrazines suitable for preparing the adducts are provided.

  提供了一种具有放射性核素标记取代基的顺-环辛烯和四氮杂环的Diels-Alder加合物，其中该加合物在动物或人体内形成。一种制备动物或人体器官PET或其他图像的方法包括在动物或人体内形成Diels-Alder加合物。提供了适用于制备加合物的顺-环辛烯和四氮杂环。
• Tetrazine-trans-cyclooctene ligation for the rapid construction of radionuclide labeled probes
  申请人：Fox Joseph M.

  公开号：US10434197B2

  公开（公告）日：2019-10-08

  A Diels-Alder adduct of a trans-cyclooctene with a tetrazine is provided, wherein the adduct bears a substituent labeled with a radionuclide. A method of producing a PET or other image of an organ in an animal or human includes forming the Diels-Alder adduct in the animal or human. Trans-cyclooctenes and tetrazines suitable for preparing the adducts are provided.

  提供了一种反式环辛烯与四嗪的 Diels-Alder 加合物，其中该加合物带有用放射性核素标记的取代基。在动物或人体内生成 PET 或其他器官图像的方法包括在动物或人体内形成 Diels-Alder 加合物。提供了适用于制备加合物的反式环辛烯和四嗪。
• Synthesis and evaluation of novel trifunctional chelating agents for pretargeting approach using albumin binder to improve tumor accumulation
  作者：Shohei Tsuchihashi、Kazuma Nakashima、Hiroyuki Watanabe、Masahiro Ono

  DOI：10.1016/j.nucmedbio.2024.108911

  日期：2024.5

  tumor-to-background ratio, but the disadvantage is to compromise tumor accumulation. In this study, we applied albumin binder (ALB) to the pretargeting approach to overcome low tumor accumulation. We synthesized two novel trifunctional effectors containing an ALB moiety, a chelator, and a different tetrazine and two corresponding effectors without an ALB moiety. Albumin-binding assays and stability assays were performed

  预靶向方法包括预注射抗体和低分子量放射性标记效应器之间的连接。预靶向方法的优点是提高肿瘤与背景的比率，但缺点是损害肿瘤积累。在这项研究中，我们将白蛋白结合剂（ALB）应用于预靶向方法以克服低肿瘤积累的问题。我们合成了两种新型三功能效应物，其中包含 ALB 部分、螯合剂和不同的四嗪，以及两种相应的不含 ALB 部分的效应物。使用In标记的效应器进行白蛋白结合测定和稳定性测定。使用In标记的效应器和环辛烯修饰的抗HER2抗体曲妥珠单抗进行反应速率常数的测量，环辛烯驱动与四嗪的点击反应。使用或不使用预靶向方法，使用表达 HER2 的荷瘤小鼠进行生物分布研究。在白蛋白结合测定中，含有 ALB 的效应子表现出与白蛋白的显着结合。两种含有 ALB 的效应子显示出反应性的差异和稳定性的轻微差异。在没有预靶向方法的生物分布研究中，两种含有 ALB 的效应物在血液滞留方面表现出不同的药代动力学。通过预靶向方法，通过引入
• Tetrazine-trans-cyclooctene ligation for the rapid construction of integrin αvβ3 targeted PET tracer based on a cyclic RGD peptide
  作者：Ramajeyam Selvaraj、Shuanglong Liu、Matthew Hassink、Chiun-wei Huang、Li-peng Yap、Ryan Park、Joseph M. Fox、Zibo Li、Peter S. Conti

  DOI：10.1016/j.bmcl.2011.04.116

  日期：2011.9

  Labeling biomolecules with F-18 is usually done through coupling with prosthetic groups, which generally requires several time-consuming radiosynthetic steps resulting in low labeling yield. Recently, the tetrazine-trans-cyclooctene ligation has been introduced as a method of bioconjugation that proceeds with fast reaction rates without need for catalysis. Herein, we report the development of an extremely fast and efficient method for generating F-18 labeled probes based on the tetrazine-trans-cyclooctene ligation. Starting with only 30 mu g (78 mu M) of a tetrazine-RGD conjugate and 2 mCi (5 mu M) of F-18-trans-cyclooctene, the F-18 labeled RGD peptide could be obtained in more than 90% yield within five minutes. The F-18 labeled RGD peptide demonstrated prominent tumor uptake in vivo. The receptor specificity was confirmed by blocking experiments. These results successfully demonstrate that the tetrazine-trans-cyclooctene ligation serves as an efficient labeling method for PET probe construction. (C) 2011 Elsevier Ltd. All rights reserved.
• TETRAZINE-TRANS-CYCLOOCTENE LIGATION FOR THE RAPID CONSTRUCTION OF RADIONUCLIDE LABELED PROBES
  申请人：University Of Delaware

  公开号：EP2595967A2

  公开（公告）日：2013-05-29