1,4-di-tert-butyl 7-(2-{[(tert-butoxy)carbonyl]amino}-3-(4-nitrophenyl)propyl)-1,4,7-triazonane-1,4-dicarboxylate | 1005484-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,4-di-tert-butyl 7-(2-{[(tert-butoxy)carbonyl]amino}-3-(4-nitrophenyl)propyl)-1,4,7-triazonane-1,4-dicarboxylate
• 英文别名: di-tert-butyl 7-[2-tert-butoxycarbonylamino-3-(4-nitrophenyl)-propyl][1,4,7]-triazacyclononane-1,4-dicarboxylate；di-tert-butyl 7-[2-tert-butoxycarbonylamino-3-(4-nitrophenyl)propyl][1,4,7]triazanonane-1,4-dicarboxylate；Ditert-butyl 7-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-nitrophenyl)propyl]-1,4,7-triazonane-1,4-dicarboxylate
• CAS: 1005484-24-1
• 化学式: C₃₀H₄₉N₅O₈
• 分子量: 607.748
• InChiKey: FYNYWGZQFFVQLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1,4-di-tert-butyl 7-(2-{[(tert-butoxy)carbonyl]amino}-3-(4-nitrophenyl)propyl)-1,4,7-triazonane-1,4-dicarboxylate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 50.0 ℃ 、137.9 kPa 条件下， 反应 103.3h， 生成 di-tert-butyl 2,2'-(7-(2-((2-(tert-butoxy)-2-oxoethyl)amino)-3-(4-((R)-4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamido)phenyl)propyl)-1,4,7-triazonane-1,4-diyl)diacetate
  参考文献：
  名称：

  Bimodal ligands with macrocyclic and acyclic binding moieties, complexes and compositions thereof, and methods of using

  摘要：

  用带有氨基或羟基的1,4,7-三氮杂环壬烷-N,N′,N″-三乙酸和1,4,7,10-四氮杂环十二烷-N,N′,N″,N′″-四乙酸化合物替代，以及它们的金属配合物、组合物、制备方法以及在诊断成像和治疗细胞疾病中的应用。

  公开号：

  US09115094B2
• 作为产物：
  描述：

  tert-butyl [2-hydroxy-1-(4-nitrobenzyl)ethyl]carbamate 在 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 2.83h， 生成 1,4-di-tert-butyl 7-(2-{[(tert-butoxy)carbonyl]amino}-3-(4-nitrophenyl)propyl)-1,4,7-triazonane-1,4-dicarboxylate
  参考文献：
  名称：

  Bimodal ligands with macrocyclic and acyclic binding moieties, complexes and compositions thereof, and methods of using

  摘要：

  用带有氨基或羟基的1,4,7-三氮杂环壬烷-N,N′,N″-三乙酸和1,4,7,10-四氮杂环十二烷-N,N′,N″,N′″-四乙酸化合物替代，以及它们的金属配合物、组合物、制备方法以及在诊断成像和治疗细胞疾病中的应用。

  公开号：

  US09115094B2

文献信息

• Synthesis and Evaluation of an Enantiomerically Enriched Bifunctional Chelator for⁶⁴Cu-Based Positron Emission Tomography (PET) Imaging
  作者：Hyun-Soon Chong、Xiang Sun、Yongliang Zhong、Kamil Bober、Michael R. Lewis、Dijie Liu、Varyanna C. Ruthengael、Inseok Sin、Chi Soo Kang

  DOI：10.1002/ejoc.201301499

  日期：2014.2

  We report the synthesis and evaluation of an enantiomerically enriched bifunctional chelator, (S)-C-NE3TA. The bifunctional chelator was efficiently prepared by regioselective and stereoselective ring opening of an aziridinium ion. The new chiral chelator instantly and almost completely bound to 64Cu at room temperature. The corresponding 64Cu-radiolabeled complex remained intact in human serum for

  我们报告了对映体富集的双功能螯合剂 (S)-C-NE3TA 的合成和评估。通过氮丙啶离子的区域选择性和立体选择性开环有效地制备了双功能螯合剂。新的手性螯合剂在室温下立即几乎完全与 64Cu 结合。相应的 64Cu 放射性标记复合物在人血清中保持完整 48 小时，没有任何可测量的转螯合，并且可以耐受严格的 EDTA 挑战 24 小时。64Cu 放射性标记的 (S)-C-NE3TA 复合物在小鼠体内是稳定的，并产生了极好的生物分布特征。体外和体内评估的结果表明，新的光学活性螯合剂是 PET 成像应用的有希望的候选者。
• Convenient Synthesis and Evaluation of a Heptadentate Bifunctional Ligand for Radioimmunotherapy Applications
  作者：Hyun-Soon Chong、Xiang Sun、Pengfei Dong、Chi Soo Kang

  DOI：10.1002/ejoc.201101063

  日期：2011.11

  An efficient synthetic route to a bifunctional chelating agent C-NE3TA-NCS for antibody-targeted radioimmunotherapy (RIT) applications was developed. Various synthetic methods centered on the key reaction steps including bimolecular cyclization, ring opening reactions of aziridine and aziridinium cations, and reductive aminiation were explored to optimize the preparation of a tetraaza-based chelate

  开发了一种用于抗体靶向放射免疫疗法 (RIT) 应用的双功能螯合剂 C-NE3TA-NCS 的有效合成路线。探索了以关键反应步骤为中心的各种合成方法，包括双分子环化、氮丙啶和氮丙啶阳离子的开环反应以及还原胺化，以优化四氮杂基螯合物 TANPA 和 C-NE3TA 类似物的制备。七齿 C-NE3TA-NCS 与肿瘤靶向抗体偶联，并与六齿 C-NOTA-NCS 进行比较，用于与镧系元素进行 RIT 的放射性标记反应动力学。与 C-NOTA 抗体偶联物相比，C-NE3TA 抗体偶联物与 90Y 的络合动力学显着增强。
• COMPOUNDS FOR POSITRON EMISSION TOMOGRAPHY
  申请人：Endocyte, Inc.

  公开号：EP3533473A2

  公开（公告）日：2019-09-04

  Described herein are compounds, compositions, and methods for diagnosing and/or monitoring pathogenic disease using positron emission tomography. Also described are conjugates of the formula B-L-P, wherein B is a radical of a targeting agent selected from vitamin receptor binding ligands (such as folate), PSMA binding ligands, or PSMA inhibitors; L is a divalent linker comprising aspartic acid, lysine, or arginine, and P is a radical of an imaging agent or radiotherapy agent, such as a radionuclide or radionuclide containing group, or a radical of a compound capable of binding a radionuclide, such as a metal chelating group.

  本文描述了利用正电子发射断层扫描诊断和/或监测致病性疾病的化合物、组合物和方法。还描述了式 B-L-P 的共轭物，其中 B 是选自维生素受体结合配体（如叶酸）、PSMA 结合配体或 PSMA 抑制剂的靶向药的基团；L 是由天冬氨酸、赖氨酸或精氨酸组成的二价连接体，P 是成像剂或放疗剂的基团，如放射性核素或含放射性核素的基团，或能结合放射性核素的化合物的基团，如金属螯合基团。
• Rational Design and Generation of a Bimodal Bifunctional Ligand for Antibody-Targeted Radiation Cancer Therapy
  作者：Hyun-Soon Chong、Xiang Ma、Thien Le、Baidoo Kwamena、Diane E. Milenic、Erik D. Brady、Hyun A. Song、Martin W. Brechbiel

  DOI：10.1021/jm070401q

  日期：2008.1.1

  An antibody-targeted radiation therapy (radioimmunotherapy, RIT) employs a bifunctional ligand that can effectively hold a cytotoxic metal with clinically acceptable complexation kinetics and stability while being attached to a tumor-specific antibody. Clinical exploration of the therapeutic potential of RIT has been challenged by the absence of adequate ligand, a critical component for enhancing the efficacy of the cancer therapy. To address this deficiency, the bifunctional ligand C-NETA in a unique structural class possessing both a macrocyclic cavity and a flexible acyclic moiety was designed. The practical, reproducible, and readily scalable synthetic route to C-NETA was developed, and its potential as the chelator of Bi-212, Bi-213, and Lu-177 for RIT was evaluated in vitro and in vivo. C-NETA rapidly binds both Lu(III) and Bi(III), and the respective metal complexes remain extremely stable in serum for 14 days. Lu-177-C-NETA and Bi-205/6-C-NETA possess an excellent or acceptable in vivo biodistribution profile.
• Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules
  申请人：McBride William J.

  公开号：US20090155166A1

  公开（公告）日：2009-06-18

  The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. The labeled molecules may be peptides or proteins, although other types of molecules may be labeled by the described methods. Preferably, the F-18 may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety. Alternatively, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other embodiments, the F-18 labeled moiety may comprise a targetable construct used in combination with a bispecific or multi specific antibody to target F-18 to a disease-associated antigen, such as a tumor-associated antigen. The F-18 labeled targetable construct peptides are stable in serum at 37° C. for a sufficient time to perform PET imaging analysis.