4-(2-carboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid | 905858-80-2

• 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: 4-(2-carboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid
• 英文别名: 4-(2-Carboxyethyl)-4-[3-(1,3-dioxoisoindol-2-yl)propanoylamino]heptanedioic acid
• CAS: 905858-80-2
• 化学式: C₂₁H₂₄N₂O₉
• 分子量: 448.43
• InChiKey: SOYKHYVGWMHGCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(2-carboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid 在 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
• 作为产物：
  描述：

  3-(N-苯二甲酰亚氨基)丙酸 在 甲酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(2-carboxyethyl)-4-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propionylamino]heptanedioic acid
  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

• Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of α_vβ₃Integrin Expression with Gallium-68
  作者：Cinzia Imberti、Samantha Y. A. Terry、Carleen Cullinane、Fiona Clarke、Georgina H. Cornish、Nisha K. Ramakrishnan、Peter Roselt、Andrew P. Cope、Rodney J. Hicks、Philip J. Blower、Michelle T. Ma

  DOI：10.1021/acs.bioconjchem.6b00621

  日期：2017.2.15

  Tris(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 (68Ga) under mild conditions, and the resulting radiotracers can delineate peptide receptor expression at sites of diseased tissue in vivo. We have synthesized a dendritic bifunctional chelator containing nine 1,6-dimethyl-3-hydroxypyridin-4-one groups (SCN-HP9) that can coordinate up to three Ga3+ ions. This derivative has been conjugated to a trimeric peptide (RGD3) containing three peptide groups that target the αvβ3 integrin receptor. The resulting dendritic compound, HP9-RGD3, can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its homologues HP3-RGD and HP3-RGD3 that contain only a single metal binding site. PET scanning and biodistribution studies show that [68Ga(HP9-RGD3)] demonstrates higher receptor-mediated tumor uptake in animals bearing U87MG tumors that overexpress αvβ3 integrin than [68Ga(HP3-RGD)] and [68Ga(HP3-RGD3)]. However, concomitant nontarget organ retention of [68Ga(HP9-RGD3)] results in low tumor to nontarget organ contrast in PET images. On the other hand, the trimeric peptide homologue containing a single tris(hydroxypyridinone) chelator, [68Ga(HP3-RGD3)], clears nontarget organs and exhibits receptor-mediated uptake in mice bearing tumors and in mice with induced rheumatoid arthritis. PET imaging with [68Ga(HP3-RGD3)] enables clear delineation of αvβ3 integrin receptor expression in vivo.

  与肽结合的三羟基吡啶酮螯合剂可以在温和的条件下快速络合正电子发射同位素镓-68（68Ga），由此产生的放射性痕量物质可以描述体内病变组织部位的肽受体表达情况。我们合成了一种含有九个 1,6-二甲基-3-羟基吡啶-4-酮基团的树枝状双功能螯合剂（SCN-HP9），它可以配位多达三个 Ga3+ 离子。这种衍生物与含有三个肽基的三聚肽（RGD3）共轭，RGD3 的目标是 αvβ3 整合素受体。由此产生的树枝状化合物 HP9-RGD3 能以 97% 的放射化学收率进行放射性标记，其特异性活性比只含有单一金属结合位点的同源物 HP3-RGD 和 -RGD3 高 3 倍。PET 扫描和生物分布研究表明，与[68Ga( -RGD)]和[68Ga( -RGD3)]相比，[68Ga(HP9-RGD3)]在过表达 αvβ3 整合素的 U87MG 肿瘤动物体内显示出更高的受体介导的肿瘤摄取率。然而，[68Ga(HP9-RGD3)]同时在非靶器官滞留会导致 PET 图像中肿瘤与非靶器官对比度较低。另一方面，含有单个三（羟基吡啶酮）螯合剂的三聚肽同源物[68Ga( -RGD3)]能清除非靶器官，并在患有肿瘤的小鼠和诱发类风湿性关节炎的小鼠中表现出受体介导的摄取。使用[68Ga( -RGD3)]进行正电子发射计算机断层成像可清楚地描述体内αvβ3整合素受体的表达。
• Synthesis, iron binding and antimicrobial properties of hexadentate 3-hydroxypyridinones-terminated dendrimers
  作者：Tao Zhou、Kai Chen、Li-Min Kong、Mu-Song Liu、Yong-Min Ma、Yuan-Yuan Xie、Robert C. Hider

  DOI：10.1016/j.bmcl.2018.05.058

  日期：2018.8

  Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron (III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric chelators were synthesized using a convergent strategy. Their iron chelating ability was demonstrated by UV/Visible spectrometry and high resolution mass spectrometry (HRMS). The iron binding affinities were also investigated by the competition with a fluorescent iron chelator CP691. The result indicated that these dendrimers possesses a high affinity for iron with a very high pFe(3+) value, which is close to that of an isolated hexadentate unit. These dendrimeric chelators were found to exhibit inhibitory effect on the growth of both Gram-positive and Gramnegative bacteria.