N,N′-[((6-carboxylato)pyridin-2-yl)methyl]-1,2-diaminoethane | 1092833-97-0

• 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: N,N′-[((6-carboxylato)pyridin-2-yl)methyl]-1,2-diaminoethane
• 英文别名: 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid；H2dedpa；6-[[2-[(6-Carboxypyridin-2-yl)methylamino]ethylamino]methyl]pyridine-2-carboxylic acid
• CAS: 1092833-97-0
• 化学式: C₁₆H₁₈N₄O₄
• 分子量: 330.343
• InChiKey: CCZACPBJJXGQBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N′-[((6-carboxylato)pyridin-2-yl)methyl]-1,2-diaminoethane 在 盐酸 作用下， 以 水 为溶剂， 以24 mg的产率得到1,2-bis([[6-(carboxy)pyridin-2-yl]methyl]amino)-ethane dichlorohydrate
  参考文献：
  名称：

  Acyclic Chelate with Ideal Properties for ⁶⁸Ga PET Imaging Agent Elaboration

  摘要：

  We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N3O3) or DOTA (N4O4) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N4O2 chelate H(2)dedpa coordinates Ga-67 quantitatively to form [Ga-67(dedpa)](+) after 10 min at RT. Concentration-dependent coordination to H(2)dedpa of either Ga-68 or Ga-67 showed quantitative conversion to the desired products with ligand concentrations as low as 10(-7) M. With Ga-68, specific activities as high as 9.8 mCi nmol(-1) were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [Ga-67(dedpa)](+) showed no decomposition. Two bifunctional versions of H(2)dedpa are also described, and these both coordinate to Ga-67 at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the Ga-67 complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA.

  DOI：

  10.1021/ja106399h
• 作为产物：
  描述：

  吡啶-2.6-二羧酸二甲酯 在 sodium tetrahydroborate 、 2-iodoxybenzoic acid 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 14.0h， 生成 N,N′-[((6-carboxylato)pyridin-2-yl)methyl]-1,2-diaminoethane
  参考文献：
  名称：

  H2depda: An acyclic adjuvant potentiates meropenem activity in vitro against metallo-β-lactamase-producing enterobacterales

  摘要：

  Metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) pose an emerging threat to public health worldwide. An effective inhibitor of MBLs is therefore urgently needed for clinical use. In this study, two acyclic pyridine-containing ligands, H(2)dedpa and compound 8, were discovered with excellent activities when combined with meropenem (MEM) against MBL (bla(NDm) and bla(IMp))-producing clinical isolates, including Escherichia coli, Citrobacter freundii, Proteus mirabilis, Enterobacter cloacae and Klebsiella pneumoniae. In particular, these two compounds improved the activity of MEM against E. coli harboring the bla(NDm-4) gene by nearly 40,960 times. H(2)dedpa (IC50 = 0.17 +/- 0.04 mu M) and compound 8 (IC50= 0.04 +/- 0.02 mu M) showed higher inhibitory activity against bla(NDm-1) enzyme than the positive control ethylenediaminetetraacetic acid (EDTA, IC50 = 28.84 +/- 0.70 mu M). A sterilization kinetics experiment showed that H(2)dedpain combined with MEM could kill 99.9% of bacteria within 24 h H(2)dedpa and compound 8 are therefore promising MBL inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.083

文献信息

• [EN] UREA-BASED PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) INHIBITORS FOR IMAGING AND THERAPY<br/>[FR] INHIBITEURS DE L'ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE (PSMA) À BASE D'URÉE, POUR IMAGERIE ET TRAITEMENT THÉRAPEUTIQUE
  申请人：FIVE ELEVEN PHARMA INC

  公开号：WO2017116994A1

  公开（公告）日：2017-07-06

  The present invention relates to compounds according to Formula I and Formula IV. These compounds display very good binding affinities to the PSMA binding sites. They can be labeled with [68Ga]GaCl3 with high yields and excellent radiochemical purity. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I or Formula IV, or a pharmaceutically acceptable salt thereof.

  本发明涉及符合式I和符合式IV的化合物。这些化合物显示出非常好的结合亲和力，能与PSMA结合位点结合。它们可以用[68Ga]GaCl3标记，产率高，放射化学纯度优秀。本发明还涉及包含药用可接受载体和符合式I或符合式IV的化合物，或其药用可接受盐的药物组合物。
• MARKING PRECURSOR WITH SQUARIC ACID COUPLING
  申请人：SCV- Spezial Chemikalien Vertrieb GmbH

  公开号：US20210369877A1

  公开（公告）日：2021-12-02

  The invention relates to a marking precursor incorporating a chelator or fluorination group for radiolabelling with 44Sc, 47Sc, 55Co, 62Cu, 64Cu, 67Cu, 66Ga, 67Ga, 68Ga, 89Zr, 86Y, 90Y, 90Nb, 99mTc, 111ln, 135Sm, 140Pr, 159Gd, 149Tb, 160Tb, 161Tb, 165Er, 166Dy, 166Ho, 175Yb, 177Lu, 186Re, 188Re, 213Bi and 225Ac or with 18F, 131I or 211At, and one or two biological targeting vectors which are coupled to the chelator or fluorinating group via one or more squaric acid groups.

  该发明涉及一种包含螯合剂或氟化基团的标记前体，用于与44Sc、47Sc、55Co、62Cu、64Cu、67Cu、66Ga、67Ga、68Ga、89Zr、86Y、90Y、90Nb、99mTc、111ln、135Sm、140Pr、159Gd、149Tb、160Tb、161Tb、165Er、166Dy、166Ho、175Yb、177Lu、186Re、188Re、213Bi和225Ac或与18F、131I或211At进行放射标记，以及一个或两个生物靶向载体，通过一个或多个方酸基团与螯合剂或氟化基团偶联。
• High-denticity ligands based on picolinic acid for ¹¹¹In radiochemistry
  作者：Eric W. Price、Cara L. Ferreira、Michael J. Adam、Chris Orvig

  DOI：10.1139/cjc-2013-0542

  日期：2014.8

  Four new acyclic ligands, Bn-H₃nonapa (3), H₃nonapa (4), p-NO₂-Bn-H₃nonapa (10), and Bn-H₃trenpa (7), were synthesized and studied with nonradioactive In³⁺ and with radioactive ¹¹¹In³⁺. The coordination of these ligands to In³⁺ was confirmed by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Radiolabeling experiments were performed with ¹¹¹In³⁺; these demonstrated H₃nonapa (4) to be the best indium ligand of those studied herein, achieving radiochemical yields of ∼97% in 10 min at ambient temperature, and stability to transchelation in mouse serum of 44.5% ± 25.9% after 24 h. Although the radiolabeling kinetics of H₃nonapa (4) were excellent, serum stability results were inferior to the previously studied ligands DOTA, DTPA, and H₄octapa, suggesting that the presented ligands may find their optimum radiopharmaceutical applications with isotopes other than ¹¹¹In. Owing to the high denticity of these ligands (9–10 coordinate), they may realize their potential with large ion isotopes such as ¹⁷⁷Lu, ^86/90Y, and ²²⁵Ac.

  四种新的无环配体，Bn-H₃nonapa（3）、H₃nonapa（4）、p-NO₂-Bn-H₃nonapa（10）和Bn-H₃trenpa（7）已经合成，并与非放射性In³⁺和放射性¹¹¹In³⁺进行了研究。这些配体与In³⁺的配位通过高分辨质谱和核磁共振光谱得到确认。用¹¹¹In³⁺进行了放射标记实验；这些实验表明H₃nonapa（4）是本研究中最好的铟配体，可在室温下10分钟内实现约97%的放射化学产率，并在小鼠血清中的转螯稳定性为44.5% ± 25.9%。尽管H₃nonapa（4）的放射标记动力学表现优异，但血清稳定性结果不及先前研究的配体DOTA、DTPA和H₄ocTApa，这表明所提出的配体可能在除了¹¹¹In之外的同位素上找到最佳的放射药物应用。由于这些配体的高配位度（9-10配位），它们可能会在大离子同位素如¹⁷⁷Lu、^86/90Y和²²⁵Ac中实现其潜力。
• [EN] PICOLINATE CROSS-BRIDGED CYCLAMS, CHELATES WITH METALLIC CATIONS AND USE THEREOF<br/>[FR] CYCLAMES PONTÉS À BRAS PICOLINATE, CHÉLATES AVEC DES CATIONS MÉTALLIQUES ET LEUR UTILISATION
  申请人：UNIVERSITÉ DE BRETAGNE OCCIDENTALE

  公开号：WO2015071334A1

  公开（公告）日：2015-05-21

  The present invention relates to chelates resulting from the complexation of picolinate cross-bridged cyclams of formula (I), wherein n and the substituents L1-L4 and R1-R5 are defined as in the claims, with metallic cations. The invention further relates to picolinate cross-bridged cyclam ligands of formula (I). Another object of the invention is the use of chelates of the invention in nuclear medicine and the use of ligands of the invention in cations detection or epuration of effluents.

  本发明涉及由式（I）的吡啶酸盐交桥环己胺络合物形成的螯合物，其中n和取代基L1-L4和R1-R5如索赔中所定义，并与金属阳离子形成络合物。该发明还涉及式（I）的吡啶酸盐交桥环己胺配体。本发明的另一个目的是将该螯合物用于核医学，将该配体用于阳离子检测或废水净化。
• H₄octapa: An Acyclic Chelator for ¹¹¹In Radiopharmaceuticals
  作者：Eric W. Price、Jacqueline F. Cawthray、Gwendolyn A. Bailey、Cara L. Ferreira、Eszter Boros、Michael J. Adam、Chris Orvig

  DOI：10.1021/ja3024725

  日期：2012.5.23

  7-coordinate solution structure, which forms a single isomer and exhibits no observable fluxional behavior at ambient temperature, an improvement to the multiple isomers formed by [In(DTPA)](2-) and [In(DOTA)](-) under the same conditions. Potentiometric titrations have determined the thermodynamic formation constant of the [In(octapa)](-) complex to be log K(ML) = 26.8(1). Through the same set of analyses,

  对具有 (111)In/(115)In(3+) 的八齿无环螯合剂 H(4)ocTApa (N(4)O(4)) 的初步研究表明，它是对现有技术缺点的改进。行业“黄金标准”DOTA (N(4)O(4)) 和 DTPA (N(3)O(5))。介绍了 H(4)ocTApa 在环境温度下在 10 分钟内定量 (111)InCl(3) 的能力，比活性高达 2.3 mCi/nmol（97.5% 放射化学产率）。体外小鼠血清稳定性测定表明，与 DOTA 和 DTPA 相比，H(4)ocTApa 的 (111)In 复合物在 24 小时内具有更高的稳定性。小鼠生物分布研究表明，与 [(111)In(DOTA)](-) 相比，放射性金属络合物 [(111)In(ocTApa)](-) 在 24 小时内具有异常高的体内稳定性，并具有更高的清除率和稳定性，24 小时时肾脏、肝脏和脾脏的摄取较低。[In(ocTApa)](-)