N3-<(2,6-dioxomorpholino)ethyl>-N6-<(ethoxycarbonyl)methyl>-3,6-diazaoctane diacid | 117185-07-6

• 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: N3-<(2,6-dioxomorpholino)ethyl>-N6-<(ethoxycarbonyl)methyl>-3,6-diazaoctane diacid
• 英文别名: N³-(2,6-dioxomorpholinoethyl)-N⁶-(ethoxycarbonylmethyl)-3,6-diazaoctanedioic acid；N3-[(2,6-dioxomorpholino)ethyl]-N6-[(ethoxycarbonyl)methyl]-3,6-diazaoctane diacid；N3-(2,6-Dioxomorpholinoethyl)-N6-(ethoxycarbonylmethyl)-3,6-diazaoctanedioic Acid；2-[2-[carboxymethyl-(2-ethoxy-2-oxoethyl)amino]ethyl-[2-(2,6-dioxomorpholin-4-yl)ethyl]amino]acetic acid
• CAS: 117185-07-6
• 化学式: C₁₆H₂₅N₃O₉
• 分子量: 403.389
• InChiKey: RQFNYUNDFYFHBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.2
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  帕米膦酸 、 N3-<(2,6-dioxomorpholino)ethyl>-N6-<(ethoxycarbonyl)methyl>-3,6-diazaoctane diacid 在 sodium hydroxide 作用下， 以 水 为溶剂， 以1.3 g的产率得到2-[2-[Bis(carboxymethyl)amino]ethyl-[2-[carboxymethyl-[2-[(3-hydroxy-3,3-diphosphonopropyl)amino]-2-oxoethyl]amino]ethyl]amino]acetic acid
  参考文献：
  名称：

  Development of phosphonate derivatives of gadolinium chelates for NMR imaging of calcified soft tissues

  摘要：

  We have synthesized several classes of gadolinium (Gd) complexes for use as NMR contrast agents in the detection of soft-tissue calcification. Class I was made up of strongly chelated GdDTPA complexes with one carboxylate arm coupled to a phosphonate-containing molecule through an amide link. Class II complexes were formed by Gd with several aminophosphonates and phosphono carboxylic acids. Class III were Gd complexes of weak chelates containing no phosphonate. The calcium-seeking ability of each complex was assessed by in vivo bone uptake. Tissue distribution in normal rats showed that only the complexes of GdDTPA modified with a diphosphonate group and GdEDTMP (EDTMP is ethylenediaminetetrakis(methylenephosponate] showed adequate bone localization at the concentrations required for NMR contrast enhancement (approximately 20% of a 100 mumol/kg dose).

  DOI：

  10.1021/jm00121a026
• 作为产物：
  描述：

  Pentetinsaeuremonoaethylester 、 吡啶 在 乙酸酐 、 乙醚 作用下， 以 乙酸酐 为溶剂， 反应 72.0h， 以18.0 g (=89% of theory) of a white powder with a melting point of 195–196° C. is obtained的产率得到N3-<(2,6-dioxomorpholino)ethyl>-N6-<(ethoxycarbonyl)methyl>-3,6-diazaoctane diacid
  参考文献：
  名称：

  DTPA monoamides, pharmaceutical agents containing these compounds, their use and process for their production

  摘要：

  式I的化合物，其中Z1、Z2、X、R2和R3如本文所定义，适用作为易感性成像中的易感性试剂。

  公开号：

  US06565830B1

文献信息

• Selective sensing of zinc ions with a novel magnetic resonance imaging contrast agent†
  作者：Kenjiro Hanaoka、Kazuya Kikuchi、Yasuteru Urano、Tetsuo Nagano

  DOI：10.1039/b100994j

  日期：——

  Light-based microscope imaging techniques using fluorescence sensor molecules suffer from photobleaching and light scattering, but magnetic resonance imaging (MRI) can provide three-dimensional imaging without these problems. Recently, “smart” MRI contrast agents which modulate the access of water to a chelated gadolinium (Gd3+) ion in the presence or absence of a specific trigger have been reported. Zinc (Zn2+) is an essential component of many enzymes, transcription factors and synaptic vesicles in excitatory nerve terminals, so imaging of chelatable Zn2+ is of interest. We have designed and synthesized the Gd3+ DTPA bisamide complex 7a as a Zn2+-sensitive MRI contrast agent. Compound 7a shows a dose-dependent change in the R1 relaxivity in the presence of Zn2+. We investigated this relaxation behavior, and for this purpose we also synthesized the Gd3+ DTPA amide ethyl ester complex 7b. It was shown that binding between 7a and Zn2+ caused a change in the relaxation time. Moreover, 7a had high selectivity for Zn2+ against Ca2+ and Mg2+. Compound 7a may have practical problems for in vivo usage, since the R1 relaxivity is reduced with increased Zn2+ concentration. However, this report demonstrates new approaches to the design and synthesis of Gd3+ complexes with R1 values that change with variation in Zn2+ concentration.

  基于光的显微镜成像技术使用荧光传感分子，但会受到光漂白和光散射的影响，而磁共振成像（MRI）则可以提供三维成像而没有这些问题。最近，报道了一种“智能”MRI对比剂，其能够在特定触发的存在或不存在下调节水分子对螯合镧（Gd3+）离子的接近。锌（Zn2+）是许多酶、转录因子和兴奋性神经末梢突触囊泡的必需成分，因此合成能够螯合Zn2+的成像探针具有重要意义。我们设计并合成了Gd3+ DTPA双酰胺复合物7a，作为Zn2+敏感的MRI对比剂。化合物7a在存在Zn2+的情况下显示出剂量依赖性的R1松弛度变化。 我们研究了这一松弛行为，为此我们还合成了Gd3+ DTPA酰胺乙基酯复合物7b。研究表明，7a与Zn2+之间的结合导致了松弛时间的变化。此外，7a对Zn2+表现出对钙离子（Ca2+）和镁离子（Mg2+）的高选择性。化合物7a在体内使用可能存在实际问题，因为R1松弛度会随着Zn2+浓度的增加而降低。然而，本报告展示了设计和合成R1值随Zn2+浓度变化的Gd3+复合物的新方法。
• Substituted porphyrin and azaporphyrin derivatives and their use in photodynamic therapy, radioimaging and MRI diagnosis
  申请人：——

  公开号：US20030100752A1

  公开（公告）日：2003-05-29

  Substituted porphyrin and azaporphyrin deviations with various substitutents in the 12- and 17-positions of the porphyrin skeleton as pharmaceutical agents for use in photodynamic therapy, MRI diagnosis, and radiodiagnostics.

  用不同的取代基替代卟啉骨架的12位和17位的卟啉和氮杂卟啉偏差作为药物代理，用于光动力疗法、MRI诊断和放射诊断。
• Use of perfluoroalkyl-containing metal complexes as contrast media in MR-imaging for visualization of plaque, tumors and necroses
  申请人：——

  公开号：US20030072713A1

  公开（公告）日：2003-04-17

  The invention relates to the use of perfluoroalkyl-containing metal complexes that have a critical micelle formation concentration <10 −3 mol/l, a hydrodynamic micelle diameter (2 Rh)>1 nm and a proton relaxivity in plasma (R 1 )>10 l/mmol·s) as contrast media in MR imaging for visualization of plaque, lymph nodes, infarcted and necrotic tissue and for independent visualization of necrotic tissue and tumor tissue.

  本发明涉及使用临界胶束形成浓度小于10-3mol/l，水动力学胶束直径（2Rh）大于1nm，血浆中质子弛豫时间（R1）大于10l/mmol·s的含有全氟烷基的金属配合物作为MR成像的对比介质，用于可视化斑块、淋巴结、梗死和坏死组织以及独立可视化坏死组织和肿瘤组织。
• Perfluoroalkyl-containing complexes with sugar radicals, process for their production and their use
  申请人：Schering AG

  公开号：US20020076379A1

  公开（公告）日：2002-06-20

  Perfluoroalkyl-containing complexes with sugar radicals of general formula I 1 in which R represents a monosaccharide or oligosaccharide radical that is bonded via the 1-OH position or 1-SH position, R f means a perfluorinated carbon chain, K is a metal complex, and Y and Z represent linker groups, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

  一般式I1的含有糖基团的全氟烷基配合物，其中R代表通过1-OH位置或1-SH位置键合的单糖或寡糖基团，Rf代表全氟碳链，K为金属配合物，Y和Z代表连接基团，适用于静脉淋巴造影、肿瘤诊断以及梗死和坏死成像。
• Neue Mittel zur Diagnose von Gefässerkrankungen
  申请人：INSTITUT FÜR DIAGNOSTIKFORSCHUNG GmbH AN DER FREIEN UNIVERSITÄT BERLIN

  公开号：EP0606683A2

  公开（公告）日：1994-07-20

  Die vorliegende Erfindung betrifft Metallkomplexe und Metallkomplex-Konjugate von Endothelinen, Endothelinderivaten, Teilsequenzen von Endothelinen, Endothelin-Analoga oder Endothelin-Antagonisten, iodierte Endothelinderivate, Teilsequenzen von Endothelinen,Endothelin-Analoga oder Endothelin-Antagonisten, sowie diese Verbindungen enthaltende Mittel, ihre Herstellung als Diagnostika, sowie Verfahren zur Herstellung dieser Verbindungen und Mittel. Dabei werden in vivo-applizierbare Metallkomplexe und Metallkomplex-Konjugate von Endothelinen, Endothelinderivaten, Teilsequenzen von Endothelinen, Endothelin-Analoga oder Endothelin-Antagonisten, sowie iodierte Endothelinderivate, Teilsequenzen von Endothelinen Endothelin-Analoga oder Endothelin-Antagonisten, vorzugsweise zur nicht-invasiven Bildgebung von Gefäßerkrankungen eingesetzt.

  本发明涉及内皮素、内皮素衍生物、内皮素部分序列、内皮素类似物或内皮素拮抗剂的金属络合物和金属络合物共轭物，碘化内皮素衍生物、内皮素部分序列、内皮素类似物或内皮素拮抗剂，以及含有这些化合物的制剂，它们作为诊断剂的制备，以及这些化合物和制剂的制备方法。 体内适用的内皮素、内皮素衍生物、内皮素部分序列、内皮素类似物或内皮素拮抗剂的金属复合物和金属复合物共轭物，以及碘化内皮素衍生物、内皮素部分序列、内皮素类似物或内皮素拮抗剂，最好用于血管疾病的无创成像。