(S)-4-benzyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid | 265648-71-3

• 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: (S)-4-benzyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid
• 英文别名: (4S)-benzyl-3,6,9-tris-(carboxymethyl)-3,6,9-triazaundecanoic acid；(S)-2-benzyl-diethylenetriamine pentaacetic acid；H5[(S)-(4-Bz)dtpa]；(S)-EOB-DTPA；H5[(S)-(4-Bz)dtpa)]；2-[2-[bis(carboxymethyl)amino]ethyl-[(2S)-2-[bis(carboxymethyl)amino]-3-phenylpropyl]amino]acetic acid
• CAS: 265648-71-3
• 化学式: C₂₁H₂₉N₃O₁₀
• 分子量: 483.475
• InChiKey: QAWHECZOIIEXPW-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  34
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  196
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (S)-4-benzyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid 在 重水 、 potassium carbonate 作用下， 反应 24.0h， 生成 H5[(S)-(4-Bz)(2H10)dtpa]
  参考文献：
  名称：

  各种苄基二亚乙基三胺五乙酸 (dtpa) 及其顺磁性配合物的合成和表征，磁共振成像的潜在造影剂

  摘要：

  Four derivatives of diethylenetriaminepentaacetic acid (= 3,6,9-tris(carboxymethyl)-3,6,9-triazaundecane-dioic acid (H(5)dtpa)), potential contrast agents for magnetic resonance imaging (MRI), carrying benzyl groups at various positions of the parent structure were synthesized and characterized by a thorough multinuclear NMR study, i.e., the (S)- and (R)-stereoisomers 1a and 1b of 4-benzyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid (H-5[(S)-(4-Bz)dtpa] and H-5[(R)-(4-Bz)dtpa] the diamide derivative N,N'-bis{[benzylcarbamoyl)methyl}diethylenetriamine-N,N',N "-triacetic acid (= 3,9-bis[2-(benzylamino)-2-oxoethyl]-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid: H-3[dtpa(BzA)(2)]: 2), and the diester derivative N,N "-bis([(benzyloxy)carbonyl]methyl]diethylenetriamine-N,N',N "-triacetic acid (= 3,9-bis[2-(benzyloxy)-2-oxoethyl]-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid; H-3[dtpa(BzE)(2)]: 3). From the O-17-NMR chemical shift of H2O induced by their dysprosium complexes with ligands 1-3, it was concluded that only one H2O molecule is contained in the first coordination sphere of these lanthanide complexes. The rotational correlation times (tau(R)) of the complexes were estimated from the H-2-NMR longitudinal relaxation rate of the deuterated diamagnetic lanthanum complexes. The exchange lime of the coordinated H2O molecule (tau(M)) was studied through the temperature dependence of the O-17-NMR transverse relaxation rate. As compared to [Gd(dtpa)](2), the H2O-exchange rate is faster fur [Gd{(S)-(4-Bz)dtpa}](2) and [Gd{(R)-(4-Bz)dtpa}](2)-, slower for [Gd{dtpa(BzA)(2)}], and almost identical for [Gd{dtpa(BzE)(2)}]. The analysis of the H-1-relaxivity of the gadolinium complexes recorded from 0.02 to 300 MHz established that i) the relaxivity of [Gd{dtpa(BzE)(2)}] is similar to that of [Gd(dtpa)](2-), ii) the slightly slower molecular rotation of [Gd{dtpa(BzA)(2)}] induces a mild enhancement of its relaxivity, and iii) the marked increase of relaxivity of [Gd{(S)-(4-Bz)dtpa}](2) and [Gd{(R)-(4-Bz)dtpa}](2-) mainly results from an apparently shorter distance between the gadolinium ion and the H2O protons of the coordinated H2O molecule.

  DOI：

  10.1002/(sici)1522-2675(20000216)83:2<394::aid-hlca394>3.0.co;2-b
• 作为产物：
  描述：

  (S)-di-tert-butyl 2,2'-(1-hydroxy-3-phenylpropan-2-ylazanediyl)diacetate 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 silver perchlorate 、 三苯基膦 作用下， 以 氯仿 、 水 、 乙腈 为溶剂， 反应 5.92h， 生成 (S)-4-benzyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid
  参考文献：
  名称：

  氮丙啶鎓开环在制备旋光二胺和三胺类似物中的应用：高效合成和评估基于DTPA的MRI造影剂。

  摘要：

  具有氮亲核试剂的氮丙啶鎓离子的开环被用于光学合成邻位二胺和二亚乙基三胺五乙酸（DTPA）类似物作为潜在的磁共振成像（MRI）造影剂的高效合成。该合成方法的特征在于，对映体富集的叠氮鎓离子的区域特异性和立体特异性亲核取代产物可以无柱分离，并且产率很高。

  DOI：

  10.1039/c5ra11306g

文献信息

• RADIOIMMUNOCONJUGATE FOR USE IN TREATING BONE MARROW ASSOCIATED DISEASES
  申请人：TheraPharm GmbH

  公开号：EP3351271A1

  公开（公告）日：2018-07-25

  The present invention relates to the use of radioimmunoconjugates for the treatment of bone marrow associated diseases, particularly AL-amyloidosis.

  本发明涉及使用放射免疫结合剂治疗骨髓相关疾病，特别是 AL 淀粉样变性。
• New Bifunctional Contrast Agents: Bis‐Amide Derivatives of <i>C</i> ‐Substituted Gd‐DTPA
  作者：Sophie Laurent、François Botteman、Luce Vander Elst、Robert N. Muller

  DOI：10.1002/ejic.200300457

  日期：2004.2

  AbstractIn order to expand upon and confirm previous observations on the positive and adverse roles played by the functionalization and substitution of the parent MRI contrast agent Gd‐DTPA, two new bi‐functionalized contrast agents namely Gd‐(S)‐EOB‐DTPA‐BMA and Gd‐(S)‐C4Bz‐DTPA‐BMA have been synthesized, purified, and characterized by multinuclear NMR studies. Water 1H nuclear magnetic relaxation dispersion profiles were recorded at several temperatures. τR was determined by 2H NMR on the diamagnetic lanthanum complex. τM, the water residence time, was obtained by 17O NMR measurements and the stability versus transmetallation by zinc was evaluated by proton relaxometry. The residence time of water molecules in the first coordination sphere of the Gd complexes has confirmed the antagonistic effects of amide functions and C‐4 substitution on the reduction of the water residence time, a critical parameter of relaxivity. This C‐4 position is thus particularly appropriate for the substitution required by the design of new contrast agents covalently bound to macromolecules or carrying specific vectors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• RADIOIMMUNOCONJUGATE FOR HUMAN CD66 FOR THE TREATMENT OF MULTIPLE MYELOMA
  申请人：Therapharm GmbH

  公开号：EP1962913A2

  公开（公告）日：2008-09-03
• IMMUNOCONJUGATE FOR HUMAN CD66 FOR THE TREATMENT OF MULTIPLE MYELOMA AND OTHER HAEMATOLOGICAL MALIGNANCIES
  申请人：Benes Ivan

  公开号：US20100183505A1

  公开（公告）日：2010-07-22

  The present invention relates to the use of radioimmunoconjugates for the treatment of haematological malignancies, particularly multiple myeloma.
• RADIOIMMUNOCONJUGATE FOR USE IN TREATING BONE MARROW ASSOCIATED DISEASES
  申请人：TheraPharm GmbH

  公开号：US20220401594A1

  公开（公告）日：2022-12-22

  The present invention relates to the use of radioimmunoconjugates for the treatment of bone marrow associated diseases, particularly AL-amyloidosis.