NOTA-bis(t-Bu)ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: NOTA-bis(t-Bu)ester
• 英文别名: Tri-tert-butyl 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetate；tert-butyl 2-[4,7-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate
• 化学式: C₂₄H₄₅N₃O₆
• 分子量: 471.638
• InChiKey: OFAPPAHQSFQUBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  NOTA-bis(t-Bu)ester 在 三氟乙酸 作用下， 反应 24.0h， 生成 1,4,7-三氮杂环壬烷-N,N',N''-三乙酸
  参考文献：
  名称：

  Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

  摘要：

  Measurement of the rate of loss of Cu-64 from the chelators used in the preparation of Cu-64-labeled proteins is critical to the development of effective Cu-64-labeled radiopharmaceuticals. Typically, however, this assessment has been made indirectly, by comparison of the relative uptake of the labeled proteins in the liver, or under non-physiological conditions such as hot 5 M HCl. In the present study, we measured the rate of loss of Cu-64 from a series of chelators (DOTA, TETA, and NOTA) that are commonly used to label proteins as a function of [Cu2+] (1, 2, and 5 mu M) and pH (7.5, 6.0. and 5.0). We found that Cu-64-NOTA is somewhat more kinetically stable than Cu-64-TETA and that both Cu-64-NOTA and Cu-64-TETA are much more kinetically stable than Cu-64-DOTA. Furthermore, the rate of loss of Cu-64 from Cu-DOTA increased with higher [Cu2+] and pH while the rate of loss of Cu-64 from Cu-TETA and Cu-NOTA was minimally dependent on [Cu2+] and pH. These results suggest that NOTA is preferable to TETA and DOTA for the preparation of Cu-64-labeled proteins. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ica.2012.07.012
• 作为产物：
  描述：

  1,4,7-triazacyclononane trihydrochloride 在 sodium carbonate 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 生成 NOTA-bis(t-Bu)ester
  参考文献：
  名称：

  Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

  摘要：

  Measurement of the rate of loss of Cu-64 from the chelators used in the preparation of Cu-64-labeled proteins is critical to the development of effective Cu-64-labeled radiopharmaceuticals. Typically, however, this assessment has been made indirectly, by comparison of the relative uptake of the labeled proteins in the liver, or under non-physiological conditions such as hot 5 M HCl. In the present study, we measured the rate of loss of Cu-64 from a series of chelators (DOTA, TETA, and NOTA) that are commonly used to label proteins as a function of [Cu2+] (1, 2, and 5 mu M) and pH (7.5, 6.0. and 5.0). We found that Cu-64-NOTA is somewhat more kinetically stable than Cu-64-TETA and that both Cu-64-NOTA and Cu-64-TETA are much more kinetically stable than Cu-64-DOTA. Furthermore, the rate of loss of Cu-64 from Cu-DOTA increased with higher [Cu2+] and pH while the rate of loss of Cu-64 from Cu-TETA and Cu-NOTA was minimally dependent on [Cu2+] and pH. These results suggest that NOTA is preferable to TETA and DOTA for the preparation of Cu-64-labeled proteins. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ica.2012.07.012

文献信息

• An Efficient Synthesis of <i>N</i> ,<i>N</i> ,<i>N</i> -Substituted 1,4,7-Triazacyclononane
  作者：Yong Huang、Yajing Liu、Song Liu、Renbo Wu、Zehui Wu

  DOI：10.1002/ejoc.201800048

  日期：2018.4.9

  A series of N,N,N‐substituted 1,4,7‐triazacyclononanes were prepared by adjusting the reaction sequences and conditions of the intermediate 1,4,7‐tribenzyl‐1,4,7‐triazonane‐2,6‐dione reduction with LiAlH4, the removal of benzyl with Pd/C, and alkylation.

  通过调节中间体1,4,7-三苄基-1,4,7-三氮杂-2-2,6-二酮的反应顺序和条件，制备了一系列N，N，N-取代的1,4,7-三氮杂环壬烷用LiAlH 4还原，用Pd / C除去苄基，并烷基化。
• 一种1,4,7-三氮杂环壬烷及其衍生物的合成 方法和所得产品
  申请人：首都医科大学

  公开号：CN108276353B

  公开（公告）日：2020-12-18

  本发明提出的1,4,7‑三氮杂环壬烷的合成方法，是以N,N'‑双(N‑苄基‑2‑氯乙酰胺)乙二胺和苄胺为原料合成中间体1,4,7‑三苄基‑1,4,7‑三氮杂环壬烷‑2,6‑二酮，后经还原去除苄基得到。此外，本发明还提出了N,N’,N”‑1,4,7‑三氮杂环壬烷衍生物的合成方法及应用该方法而得到相应的产品。本发明成本低；可操作性强；反应条件可控、选择性的合成带有不同取代基的N,N’,N”‑1,4,7‑三氮杂环壬烷衍生物；可适用于工业生产；适用于不同取代基的不同类型的三氮杂环壬烷衍生物合成，具有较大实施价值和效益，该产品在放射性药物化学多功能螯合剂、离子识别和配位化学等领域具有潜在应用价值。
• Stable aluminium fluoride chelates with triazacyclononane derivatives proved by X-ray crystallography and 18F-labeling study
  作者：Dinesh Shetty、Soo Young Choi、Jae Min Jeong、Ji Youn Lee、Lathika Hoigebazar、Yun-Sang Lee、Dong Soo Lee、June-Key Chung、Myung Chul Lee、Young Keun Chung

  DOI：10.1039/c1cc13151f

  日期：——

  A single crystal structure of an aluminium-fluoride complex of a model compound (NODA-benzyl) was studied to understand the co-ordination chemistry. Series of ligands with an extra carboxylic acid linker for biomolecule conjugation were studied for improved 18F-labeling applications.

  研究了模型化合物（NODA-苄基）的铝氟化物络合物的单晶结构，以了解配位化学。研究了用于生物分子缀合的带有额外羧酸连接体的一系列配体，以改进 18F 标记应用。
• Preclinical Evaluation of [⁶⁴Cu]NOTA-CP01 as a PET Imaging Agent for Metastatic Esophageal Squamous Cell Carcinoma
  作者：Tukang Peng、Xiaohui Wang、Zhijun Li、Lei Bi、Jiebing Gao、Min Yang、Yuwei Wang、Xiaojun Yao、Hong Shan、Hongjun Jin

  DOI：10.1021/acs.molpharmaceut.1c00600

  日期：2021.9.6

  the prolonged-time images showed that there was obvious radioactivity accumulation in the tumor (1.27 ± 0.19%ID/g) with the best tumor-to-blood ratio (4.79 ± 0.06) and tumor-to-muscle ratio (15.44 ± 2.94) at 6 h postinjection of the probe. The immunofluorescence and immunohistochemistry confirmed the positive expression of CXCR4 in the EC109 tumor and ESCC and metastatic lymph nodes of patients, respectively

  靶向转移性食管鳞状细胞癌（ESCC）一直是临床实践中的挑战。新出现的证据表明，CXC 趋化因子受体 4 (CXCR4) 在 ESCC 中高表达，在肿瘤转移过程中起关键作用。我们开发了一种源自 LY2510924（一种基于环肽的 CXCR4 强效拮抗剂）的 NOTA-CP01 的铜 64 ( t 1/2 = 12.7 h, 19% β + ) 标记途径，试图无创地观察转移性 ESCC 中的 CXCR4 表达。前体 NOTA-CP01 是通过修改 LY2510925 的 C 端与 bis- t-丁基 NOTA 通过丁烷-1,4-二胺接头。放射性标记过程在 15 分钟内完成，具有高放射化学产率 (>95%)、放射化学纯度 (>99%) 和比活度 (10.5–21 GBq/μmol)（未经过衰减校正）。体外溶解度和稳定性测试表明，[ 64 Cu ]NOTA-CP01 具有高水溶性（log  P =
• Efficient synthesis and evaluation of bimodal ligand NETA
  作者：Hyun-Soon Chong、Hyun A. Song、Noah Birch、Thien Le、Sooyoun Lim、Xiang Ma

  DOI：10.1016/j.bmcl.2008.03.084

  日期：2008.6

  The efficient and short synthetic route to the structurally novel bimodal ligand NETA for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer was developed. The structure of NETA was determined by X-ray crystallography. The arsenazo-based UV spectroscopic complexation kinetics data suggest that NETA is a promising chelator for use in RIT applications of (212)Bi, (213)Bi, and (177)Lu. (c) 2008 Published by Elsevier Ltd.