N,N'-(benzyl)-N,N'-[(tert-butoxycarbonyl)methyl]ethylenediamine | 1171249-41-4

• 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'-(benzyl)-N,N'-[(tert-butoxycarbonyl)methyl]ethylenediamine
• 英文别名: di-tert-butyl N,N'-dibenzylethylenediamine-N,N'-diacetate；N,N'-dibenzyl-N,N'-di-(tert-butyl acetate)ethylendiamine；N,N'-dibenzyl-N,N'-di(tert-butyl acetate)ethylendiamine
• CAS: 1171249-41-4
• 化学式: C₂₈H₄₀N₂O₄
• 分子量: 468.637
• InChiKey: BUKHYLJYFAMZRA-UHFFFAOYSA-N

物化性质

• 熔点：
  68 °C(Solv: methanol (67-56-1))
• 沸点：
  529.8±50.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.67
• 重原子数：
  34.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.08
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N,N'-(benzyl)-N,N'-[(tert-butoxycarbonyl)methyl]ethylenediamine 在 甲酸 、 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 反应 6.5h， 生成 di-tert-butyl 2,2'-(6-(2-tert-butoxy-2-oxoethylamino)-6-methyl-1,4-diazepane-1,4-diyl)diacetate
  参考文献：
  名称：

  新的DATAm和DATA5m配体形成的镓（III）和一些二价金属配合物的平衡，动力学和结构性质

  摘要：

  发展68锗/ 68镓发生器取得了正电子发射68嘎同位素广泛接受，并提出在嘎新的螯合物的兴趣3+。六齿1,4-二（乙酸）-6-甲基[氨基（乙酸）酯]过氢-1,4-二氮杂（（DATA m）配体及其双功能类似物1,4-二（乙酸）-6-戊酸酸[氨基（甲基）乙酸盐]过氢-1,4-二氮杂pan烷（DATA 5m）以高放射化学产率快速形成68 Ga的配合物。Ga 3+，Zn 2 +，Cu 2 +，Mn形成的DATA m和DATA 5m配合物的稳定常数通过使用pH电位法，分光光度法（Cu 2+）以及1 H和71 Ga NMR光谱法（Ga 3+）测定2+和Ca 2+。Ga（DATA m）和Ga（DATA 5m）配合物的稳定常数略高于Ga（AAZTA）的稳定常数。物种分布计算表明，在生理pH下，Ga（L）OH混合羟基复合物占主导地位。的1 H和71Ga NMR光谱研究提供了有关配体配位官能团以及Ga（L）和G

  DOI：

  10.1002/chem.201701508
• 作为产物：
  描述：

  苯甲醛 在 sodium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 N,N'-(benzyl)-N,N'-[(tert-butoxycarbonyl)methyl]ethylenediamine
  参考文献：
  名称：

  H4octapa：111In 放射性药物的无环螯合剂

  摘要：

  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)](-)

  DOI：

  10.1021/ja3024725

文献信息

• Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach
  作者：Hanane Lahnif、Tilmann Grus、Stefanie Pektor、Lukas Greifenstein、Mathias Schreckenberger、Frank Rösch

  DOI：10.3390/molecules26216332

  日期：——

  (1) Background: Prostate-specific membrane antigen (PSMA) has been extensively studied in the last decade. It became a promising biological target in the diagnosis and therapy of PSMA-expressing cancer diseases. Although there are several radiolabeled PSMA inhibitors available, the search for new compounds with improved pharmacokinetic properties and simplified synthesis is still ongoing. In this study, we developed PSMA ligands with two different hybrid chelators and a modified linker. Both compounds have displayed a promising pharmacokinetic profile. (2) Methods: DATA5m.SA.KuE and AAZTA5.SA.KuE were synthesized. DATA5m.SA.KuE was labeled with gallium-68 and radiochemical yields of various amounts of precursor at different temperatures were determined. Complex stability in phosphate-buffered saline (PBS) and human serum (HS) was examined at 37 °C. Binding affinity and internalization ratio were determined in in vitro assays using PSMA-positive LNCaP cells. Tumor accumulation and biodistribution were evaluated in vivo and ex vivo using an LNCaP Balb/c nude mouse model. All experiments were conducted with PSMA-11 as reference. (3) Results: DATA5m.SA.KuE was synthesized successfully. AAZTA5.SA.KuE was synthesized and labeled according to the literature. Radiolabeling of DATA5m.SA.KuE with gallium-68 was performed in ammonium acetate buffer (1 M, pH 5.5). High radiochemical yields (>98%) were obtained with 5 nmol at 70 °C, 15 nmol at 50 °C, and 60 nmol (50 µg) at room temperature. [68Ga]Ga-DATA5m.SA.KuE was stable in human serum as well as in PBS after 120 min. PSMA binding affinities of AAZTA5.SA.KuE and DATA5m.SA.KuE were in the nanomolar range. PSMA-specific internalization ratio was comparable to PSMA-11. In vivo and ex vivo studies of [177Lu]Lu-AAZTA5.SA.KuE, [44Sc]Sc-AAZTA5.SA.KuE and [68Ga]Ga-DATA5m.SA.KuE displayed specific accumulation in the tumor along with fast clearance and reduced off-target uptake. (4) Conclusions: Both KuE-conjugates showed promising properties especially in vivo allowing for translational theranostic use.

  (1) 背景：前列腺特异性膜抗原（PSMA）在过去十年中得到了广泛研究。它成为了诊断和治疗表达PSMA的癌症疾病的有希望的生物靶点。尽管已经有几种放射标记的PSMA抑制剂可用，但寻找具有改进药代动力学特性和简化合成的新化合物仍在进行中。在这项研究中，我们开发了具有两种不同混合螯合剂和改良连接剂的PSMA配体。这两种化合物都显示出有希望的药代动力学特性。（2）方法：合成了DATA5m.SA.KuE和AAZTA5.SA.KuE。将DATA5m.SA.KuE用镓-68标记，并确定了在不同温度下不同量的前体的放射化学产率。在磷酸盐缓冲液（PBS）和人血清（HS）中检查了复合物在37°C下的稳定性。使用PSMA阳性的LNCaP细胞在体外实验中确定了结合亲和力和内化比。使用LNCaP Balb/c裸鼠模型在体内和体外评估了肿瘤积聚和生物分布。所有实验均以PSMA-11作为参考。（3）结果：成功合成了DATA5m.SA.KuE。根据文献合成了AAZTA5.SA.KuE并进行了标记。在乙酸铵缓冲液（1 M，pH 5.5）中对DATA5m.SA.KuE进行了镓-68的放射标记。在70°C下使用5 nmol，在50°C下使用15 nmol，在室温下使用60 nmol（50 µg）获得了高放射化学产率（>98%）。[68Ga]Ga-DATA5m.SA.KuE在人血清以及PBS中在120分钟后仍保持稳定。AAZTA5.SA.KuE和DATA5m.SA.KuE的PSMA结合亲和力在纳摩尔范围内。PSMA特异性内化比与PSMA-11相当。[177Lu]Lu-AAZTA5.SA.KuE、[44Sc]Sc-AAZTA5.SA.KuE和[68Ga]Ga-DATA5m.SA.KuE的体内和体外研究显示出在肿瘤中特异性积聚以及快速清除和减少非靶向摄取。（4）结论：两种KuE结合物在体内表现出有希望的特性，特别适用于转化治疗诊断用途。
• An efficient route to pyridine and 2,2′-bipyridine macrocycles incorporating a triethylenetetraminetetraacetic acid core as ligand for lanthanide ions
  作者：Ghassan Bechara、Nadine Leygue、Chantal Galaup、Béatrice Mestre、Claude Picard

  DOI：10.1016/j.tetlet.2009.09.030

  日期：2009.11

  Two novel macrocyclic chelators L-1 and L-2 incorporating an intracyclic pyridine or 2,2'-bipyridine unit and a triethylenetetraminetetraacetic acid core (TITA) were synthesized with the aim of forming lanthanide complexes suitable as efficient long-lived luminophores. For this goal, an efficient methodology for the preparation of TITA derivatives using prealkylated precursors is described Starting from commercially available compounds, the target ligands were obtained in seven (L-1) and nine (L-2) steps in 40% and 20% overall yields. respectively. Stable Tb(III) complexes were prepared and displayed interesting luminescence properties. (C) 2009 Elsevier Ltd All rights reserved
• Polyazamacrocycles based on a tetraaminoacetate moiety and a (poly)pyridine intracyclic unit: direct synthesis and application to the photosensitization of Eu(III) and Tb(III) ions in aqueous solutions
  作者：Ghassan Bechara、Nadine Leygue、Chantal Galaup、Béatrice Mestre-Voegtlé、Claude Picard

  DOI：10.1016/j.tet.2010.09.052

  日期：2010.11

  A series of five new 15-, 18- or 21-membered polyazamacrocycles (L-1-L-5) based on a pyridine, bipyridine or terpyridine unit and a triethylenetetraminetetraacetic acid (TTTA) skeleton is described. In ligands L-4 and L-5 the azaheterocycle contains an additional extracyclic functionality (ester group) suitable for covalently attachment to bioactive molecules. The synthetic procedure is based on the use of a linear tetra-N-alkylated tetramine synthon incorporating masked acetate arms and an efficient metal template ion effect, which controls the crucial macrocyclization step. In the case of L-1-L-3, the formation of lanthanide complexes with europium(III) and terbium(III) was investigated and the fluorescence characteristics of the complexes were established. In this series, the terbium(III) complex derived from the bipyridine ligand exhibits the highest lifetime and quantum yield values (tau=2.18 ms, Phi=26%). (C) 2010 Elsevier Ltd. All rights reserved.