N,N'-Bis[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethyl]-4-(3-aminopropionylamino)-4-[3-oxo-3-[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethylamino]propyl]heptanediamide | 827331-42-0

• 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: N,N'-Bis[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethyl]-4-(3-aminopropionylamino)-4-[3-oxo-3-[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethylamino]propyl]heptanediamide
• 英文别名: 4-(3-aminopropanoylamino)-N,N'-bis[(1,6-dimethyl-4-oxo-3-phenylmethoxypyridin-2-yl)methyl]-4-[3-[(1,6-dimethyl-4-oxo-3-phenylmethoxypyridin-2-yl)methylamino]-3-oxopropyl]heptanediamide
• CAS: 827331-42-0
• 化学式: C₅₈H₇₀N₈O₁₀
• 分子量: 1039.24
• InChiKey: JWPKZNZKFVFTTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  76
• 可旋转键数：
  27
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  231
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N,N'-Bis[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethyl]-4-(3-aminopropionylamino)-4-[3-oxo-3-[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethylamino]propyl]heptanediamide 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以99 %的产率得到
  参考文献：
  名称：

  Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

  摘要：

  两种 68Ga 放射性标记的整合素 αvβ6 肽-THPs，利用 THP 化学快速、高效和稳定的镓螯合作用，实现对跨膜受体 αvβ6 整合素的体内监测。

  DOI：

  10.1039/d2dt00980c
• 作为产物：
  描述：

  4-(2-tert-butoxycarboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid di-tert-butyl ester 在 甲酸 、 1-羟基苯并三唑 、 一水合肼 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 N,N'-Bis[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethyl]-4-(3-aminopropionylamino)-4-[3-oxo-3-[1,6-dimethyl-3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-ylmethylamino]propyl]heptanediamide
  参考文献：
  名称：

  Iron Binding Dendrimers:  A Novel Approach for the Treatment of Haemochromatosis

  摘要：

  A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.

  DOI：

  10.1021/jm0600949

文献信息

• CONJUGATES AND THEIR USES IN MOLECULAR IMAGING
  申请人：Ballinger James Russell

  公开号：US20140056810A1

  公开（公告）日：2014-02-27

  The present invention relates to bifunctional compounds, the bifunctional compounds for use in molecular imaging and therapy, methods of molecular imaging using the bifunctional compounds and kits including the bifunctional compounds for use molecular imaging. The bifunctional compounds have a tripodal hydroxypyridinone chelating portion and may be conjugated to a targeting group so that the compounds target specific cells or tissues in a subject.

  本发明涉及双功能化合物，该双功能化合物用于分子成像和治疗，使用该双功能化合物进行分子成像的方法以及包括用于分子成像的双功能化合物的试剂盒。这些双功能化合物具有三脚架羟基吡啶酮螯合部分，并且可以与靶向基团偶联，以使化合物靶向主体中的特定细胞或组织。
• Efficient bifunctional gallium-68 chelators for positron emission tomography: tris(hydroxypyridinone) ligands
  作者：David J. Berry、Yongmin Ma、James R. Ballinger、Richard Tavaré、Alexander Koers、Kavitha Sunassee、Tao Zhou、Saima Nawaz、Gregory E. D. Mullen、Robert C. Hider、Philip J. Blower

  DOI：10.1039/c1cc12123e

  日期：——

  A new tripodal tris(hydroxypyridinone) bifunctional chelator for gallium allows easy production of 68Ga-labelled proteins rapidly under mild conditions in high yields at exceptionally high specific activity and low concentration.

  一种新型三元三（羟基吡啶酮）双功能镓螯合剂可在温和的条件下以极高的比活度和低浓度快速、高产率生产 68Ga 标记的蛋白质。
• Fluorescent 3-hydroxy-4-pyridinone hexadentate iron chelators: intracellular distribution and the relevance to antimycobacterial properties
  作者：Ana Nunes、Maria Podinovskaia、Andreia Leite、Paula Gameiro、Tao Zhou、Yongmin Ma、Xiaole Kong、Ulrich E. Schaible、Robert C. Hider、Maria Rangel

  DOI：10.1007/s00775-010-0650-1

  日期：2010.8

  hexadentate unit (3) and the corresponding rhodamine B (4) and fluorescein (5) labelled chelators. The iron(III) stability constant was determined for 3 and the values log β = 34.4 and pFe3+ = 29.8 indicate an affinity for iron of the same order of magnitude as that of mycobacteria siderophores. Fluorescence properties in the presence of liposomes show that 4 strongly interacts with the lipid phase, whereas

  摘要我们报告了荧光铁螯合剂的合成和表征（4），显示出可有效抑制鸟分枝杆菌的生长。在巨噬细胞中的合成，以及两种不成功的类似物的合成和表征，这些类似物的选择有利于鉴定负责抗菌活性的分子特性。研究了螯合剂在脂质体中的分配，并通过流式细胞术和共聚焦显微镜检查了这些化合物在巨噬细胞摄取，对铁超载/铁剥夺的反应性以及细胞内分布方面的作用。六齿螯合剂的合成基于四面体结构，三个二齿3-羟基-4-吡啶酮螯合单元通过酰胺键连接。该结构具有合成通用性，可以进一步添加官能团，例如荧光团。在这里，我们分析非功能化的六齿单元（3）和相应的若丹明B（4）和荧光素（5）标记的螯合剂。铁（III）的稳定常数被确定为3，其值记录 β  = 34.4和PFE 3+  = 29.8指示量值作为分枝杆菌铁载体的相同的顺序的铁的亲和力。在脂质体存在下的荧光性质表明，4与脂质相强烈相互作用，而5没有。这种不同的行为可以解释其共聚焦显微
• A novel method for non-transferrin-bound iron quantification by chelatable fluorescent beads based on flow cytometry
  作者：Yongmin Ma、Maria Podinovskaia、Patricia J. Evans、Giovanni Emma、Ulrich E. Schaible、John Porter、Robert C. Hider

  DOI：10.1042/bj20140795

  日期：2014.11.1

  The reliable measurement of non-transferrin-bound iron (NTBI) in serum has proved to be difficult and generally time consuming. We have sought a simple and fast method for such a determination. We adopted a fluorescence assay and designed a fluorescent dye with a chelating agent attached to sense iron. To avoid autofluorescence from serum samples, the iron probes were linked to beads and the autofluorescence could be separated and excluded from the measurement by flow cytometry due to the size difference between beads and serum proteins. Fluorescent beads containing both fluorescent and chelating moieties have been synthesized. The nature of the chelating function has been systematically investigated using four different chelators: bidentate hydroxypyranone, bidentate hydroxypyridinone, hexadentate hydroxypyranone and hexadentate hydroxypyridinone, each with different iron affinity constants. Competition studies demonstrate that the hexadentate hydroxypyridinone-based beads are capable of scavenging most of low molecular mass and albumin-bound iron but negligible amounts of iron from transferrin and ferritin. Serum samples from 30 patients with different types of disease and normal volunteers were measured. The concentrations of NTBI fall in the range −0.41 to +6.5 μM. The data have been compared with those obtained from the traditional ‘NTA’ method.

  对血清中的非转铁蛋白结合铁（NTBI）进行可靠的测定已被证明是一件非常困难的事情，而且一般都比较耗时。我们一直在寻找一种简单、快速的测定方法。我们采用了荧光检测法，并设计了一种附有螯合剂的荧光染料来感知铁。为了避免血清样本中的自发荧光，铁探针被连接到珠子上，由于珠子和血清蛋白之间的尺寸差异，自发荧光可以被分离出来，并排除在流式细胞仪的测量之外。我们已经合成了同时含有荧光和螯合分子的荧光珠。我们使用四种不同的螯合剂系统地研究了螯合功能的性质：双叉羟基吡喃酮、双叉羟基吡啶酮、六位羟基吡喃酮和六位羟基吡啶酮，每种螯合剂都具有不同的铁亲和常数。竞争研究表明，基于六齿羟基吡啶酮的珠子能够清除大部分低分子质量和白蛋白结合的铁，但从转铁蛋白和铁蛋白中清除的铁微乎其微。对 30 名不同类型疾病患者和正常志愿者的血清样本进行了测量。NTBI 的浓度范围为 -0.41 至 +6.5 μM。这些数据与传统的 "NTA "方法得出的数据进行了比较。
• METHODS AND KITS FOR PREPARING RADIONUCLIDE COMPLEXES
  申请人：THERAGNOSTICS LIMITED

  公开号：US20180092996A1

  公开（公告）日：2018-04-05

  A method for preparing a complex comprising a radioisotope of gallium for use in radiotherapy or in a medical imaging procedure, said method comprising adding a gallium radioisotope solution obtained directly from a gallium radionuclide generator to a composition comprising a pharmaceutically acceptable buffer and optionally also a pharmaceutically acceptable basic reagent, in amounts sufficient to increase the pH to a level in the range of 3 to 8, wherein the composition further comprises a chelator that is able to chelate radioactive gallium within said pH range and at moderate temperature, said chelator being optionally linked to a biological targeting agent.