6,6'-((1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid | 1128304-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6,6'-((1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid
• 英文别名: 6,6'-[1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diylbis(methylene)]dipyridine-2-carboxylic acid；macropa；6-[[16-[(6-carboxypyridin-2-yl)methyl]-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-7-yl]methyl]pyridine-2-carboxylic acid
• CAS: 1128304-86-8
• 化学式: C₂₆H₃₆N₄O₈
• 分子量: 532.594
• InChiKey: AHJIXPVAMVLFOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  6,6'-((1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid 在 三乙胺 、 barium perchlorate trihydrate 作用下， 以 异丙醇 为溶剂， 反应 1.42h， 以0.0206 g的产率得到
  参考文献：
  名称：

  Rapid Dissolution of BaSO₄ by Macropa, an 18-Membered Macrocycle with High Affinity for Ba²⁺

  摘要：

  Insoluble BaSO4 scale is a costly and time-consuming problem in the petroleum industry. Clearance of BaSO4-impeded pipelines requires chelating agents that can efficiently bind Ba2+, the largest nonradioactive +2 metal ion. Due to the poor affinity of currently available chelating agents for Ba2+, however, the dissolution of BaSO4 remains inefficient, requiring very basic solutions of ligands. In this study, we investigated three diaza-18-crown-6 macrocycles bearing different pendent arms for the chelation of Ba2+ and assessed their potential for dissolving BaSO4 scale. Remarkably, the bis-picolinate ligand macropa exhibits the highest affinity reported to date for Ba2+ at pH 7.4 (log K' = 10.74), forming a complex of significant kinetic stability with this large metal ion. Furthermore, the BaSO4 dissolution properties of macropa dramatically surpass those of the state-of-the-art ligands DTPA and DOTA. Using macropa, complete dissolution of a molar equivalent of BaSO4 is reached within 30 min at room temperature in pH 8 buffer, conditions under which DTPA and DOTA only achieve 40% dissolution of BaSO4. When further applied for the dissolution of natural barite, macropa also outperforms DTPA, showing that this ligand is potentially valuable for industrial processes. Collectively, this work demonstrates that macropa is a highly effective chelator for Ba2+ that can be applied for the remediation of BaSO4 scale.

  DOI：

  10.1021/jacs.8b08704

文献信息

• MACROCYCLIC COMPLEXES OF ALPHA-EMITTING RADIONUCLIDES AND THEIR USE IN TARGETED RADIOTHERAPY OF CANCER
  申请人：Cornell University

  公开号：US20200157087A1

  公开（公告）日：2020-05-21

  The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, wherein M 1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

  当前技术提供了化合物以及包括这些化合物的组合物，这些化合物在针对过表达前列腺特异性膜抗原（“PSMA”）的癌症和/或哺乳动物组织的靶向放射治疗中有用，其中这些化合物由以下表示：或其药用可接受盐，或其药用可接受盐，或其药用可接受盐，其中M1在每次出现时独立地是一个α放射性核素。还披露了这些化合物的等效物。
• [EN] MACROCYCLIC CHELATORS AND METHODS OF USE THEREOF<br/>[FR] CHÉLATEURS MACROCYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：JANSSEN BIOTECH INC

  公开号：WO2020229974A1

  公开（公告）日：2020-11-19

  Macrocyclic chelators (I) for chelation of alpha-emitting radiometal ions, such as actinium-225 are provided. Also provided are radiometal complexes containing an alpha-emitting radiometal ion bound to the macrocyclic chelator via coordinate bonding, and radioimmunoconjugates containing the radiometal complexes covalently linked to a targeting ligand, such as an antibody or antigen binding fragment thereof. The radioimmunoconjugates can be produced by click chemistry reactions. Methods of using the radiocomplexes and radioimmunoconjugates for selectively targeting neoplastic cells for radiotherapy and for treating neoplastic diseases and disorders are also described.

  提供了用于螯合α放射性金属离子（如锕-225）的大环螯合剂（I）。还提供了包含α放射性金属离子与大环螯合剂通过配位键结合的放射金属配合物，以及包含放射金属配合物共价连接到靶向配体（如抗体或其抗原结合片段）的放射免疫结合物。这些放射免疫结合物可以通过点击化学反应制备。还描述了利用这些放射金属配合物和放射免疫结合物用于选择性靶向肿瘤细胞进行放射治疗以及治疗肿瘤疾病和疾病的方法。
• [EN] CHELATORS AND METHODS OF MAKING AND USING SAME<br/>[FR] CHÉLATEURS ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：UNIV BRITISH COLUMBIA

  公开号：WO2020186328A1

  公开（公告）日：2020-09-24

  A chelating agent having the general formula (I) is provided (I) Metal chelates and constructs for carrying out targeted radionuclide therapy incorporating such chelating agents are provided. Methods of making and using the chelating agent, metal chelates and constructs for carrying out targeted radionuclide therapy, as well as diagnostic and therapeutic methods using such constructs, are provided.

  提供了具有一般公式（I）的螯合剂（I），提供了金属螯合物和用于进行靶向放射性核素治疗的构造物。提供了制备和使用螯合剂、金属螯合物和构造物进行靶向放射性核素治疗的方法，以及使用这些构造物的诊断和治疗方法。
• [EN] DIAZA-18-CROWN-6 DERIVATIVE USEFUL FOR CHELATING RADIUM, CONJUGATE AND RADIUM CHELATE COMPRISING THE SAME, AND USES THEREOF<br/>[FR] DÉRIVÉ DE DIAZA-18-CROWN-6 UTILE POUR CHÉLATER LE RADIUM, CONJUGUÉ ET CHÉLATE DE RADIUM COMPRENANT CE DÉRIVÉ ET UTILISATIONS CORRESPONDANTES
  申请人：ORANO

  公开号：WO2021250240A1

  公开（公告）日：2021-12-16

  The invention relates to a diaza-18-crown-6 derivative having formula (I): wherein: B is a moiety for a covalent bonding reaction; the two A are identical to each other and are a group of formula (II): where: n = 0 to 4; X1, X2, X3, X4 and X5 are N, a -CH group or a -CR group wherein R is a -P(O)(OR1)(OR2), -P(O)R1(OR2), -P(O)R1R2, -P(S)(SR1)(SR2), -P(S)R1(SR2) or -P(S)R1R2 group in which R1 and R2, identical or different, are H, or a C1-C4 alkyl group, provided that no more than two of X1, X2, X3, X4 and X5 are N and no more than one of X1, X2, X3, X4 and X5 is a -CR group. The invention also relates to a conjugate comprising the diaza-18-crown-6 derivative covalently bonded to a targeting moiety for biological cells, a chelate comprising radium chelated by the conjugate, and to uses of the diaza-18-crown-6 derivative, the conjugate and the chelate.

  这项发明涉及具有以下式（I）的二氮杂-18-冠-6衍生物：其中：B是用于共价键合反应的基团；两个A相互相同，是式（II）的一个基团：其中：n = 0至4；X1、X2、X3、X4和X5是N、-CH基团或-CR基团，其中R是-P(O)(OR1)(OR2)、-P(O)R1(OR2)、-P(O)R1R2、-P(S)(SR1)(SR2)、-P(S)R1(SR2)或-P(S)R1R2基团，其中R1和R2，相同或不同，是H，或C1-C4烷基基团，前提是X1、X2、X3、X4和X5中不超过两个是N，且X1、X2、X3、X4和X5中不超过一个是-CR基团。该发明还涉及将二氮杂-18-冠-6衍生物共价键合到生物细胞靶向基团的共轭物，包括由该共轭物螯合的镭的螯合物，以及二氮杂-18-冠-6衍生物、共轭物和螯合物的用途。
• Tuning the Kinetic Inertness of Bi³⁺ Complexes: The Impact of Donor Atoms on Diaza-18-Crown-6 Ligands as Chelators for ²¹³Bi Targeted Alpha Therapy
  作者：David J. Fiszbein、Victoria Brown、Nikki A. Thiele、Joshua J. Woods、Luke Wharton、Samantha N. MacMillan、Valery Radchenko、Caterina F. Ramogida、Justin J. Wilson

  DOI：10.1021/acs.inorgchem.1c01269

  日期：2021.6.21

  for targeted α therapy (TAT): a type of nuclear medicine that harnesses α particles to eradicate cancer cells. To use this radionuclide for this application, a bifunctional chelator (BFC) is needed to attach it to a biological targeting vector that can deliver it selectively to cancer cells. Here, we investigated six macrocyclic ligands as potential BFCs, fully characterizing the Bi3+ complexes by NMR

  放射性核素213 Bi 可用于靶向 α 治疗 (TAT)：一种利用 α 粒子根除癌细胞的核医学。要将这种放射性核素用于该应用，需要一种双功能螯合剂 (BFC) 将其附着在生物靶向载体上，从而选择性地将其递送至癌细胞。在这里，我们研究了六种大环配体作为潜在的 BFC，通过 NMR 光谱、质谱和元素分析充分表征了 Bi 3+配合物。三个配合物的固态结构揭示了由立体化学活性 6s 2孤对引起的 Bi 3+中心的配位几何结构扭曲。Bi 3+的动力学性质通过用 1000 倍过量的螯合剂二亚乙基三胺五乙酸 (DTPA) 挑战它们来评估复合物。最动力学惰性的配合物包含最基本的悬垂供体。密度泛函理论（DFT）和分子中原子的量子理论（QTAIM）计算被用来研究这一趋势，表明动力学惰性与 6s 2孤对立体化学活性的程度无关，而与共价的程度有关悬垂捐助者之间。最后，213 Bi (30–210 kBq) 与三种