钆噻酸 | 158599-72-5

• 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
• 中文名称: 钆噻酸
• 英文名称: (S)-2,2'-((2-((2-(bis(carboxymethyl)amino)-3-(4-ethoxyphenyl)propyl)(carboxymethyl)amino)ethyl)azanediyl)diacetic acid
• 英文别名: 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecandioic acid；(S)-EOB-DTPA；EOB-DTPA；2-[[(2S)-2-[bis(carboxymethyl)amino]-3-(4-ethoxyphenyl)propyl]-[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid
• CAS: 158599-72-5
• 化学式: C₂₃H₃₃N₃O₁₁
• 分子量: 527.529
• InChiKey: AQOXEJNYXXLRQQ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.2
• 重原子数：
  37
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  205
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  钆噻酸 在 吡啶 、 乙酸酐 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 3,6,9-tris(carboxymethyl)-4-ethoxybenzyl-1,11-bis(methylamino)-3,6,9-triazaundeca-1,11-dione
  参考文献：
  名称：

  New Bifunctional Contrast Agents: Bis‐Amide Derivatives of C ‐Substituted Gd‐DTPA

  摘要：

  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)

  DOI：

  10.1002/ejic.200300457
• 作为产物：
  描述：

  Z-L-酪氨酸甲酯 在 盐酸 、 甲醇 、 sodium tetrahydroborate 、 sodium hydride 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 44.16h， 生成 钆噻酸
  参考文献：
  名称：

  EOB-DTPA의 신규 제조방법

  摘要：

  这项发明涉及使用新型中间体有效且经济地制备EOB-DTPA的方法。该发明的方法可以进行原位过程，显著减少乙二胺的使用量，不使用昂贵的催化剂和试剂，并且排除了存在爆炸风险的氢反应过程，因此非常优越。

  公开号：

  KR102137340B1

文献信息

• [EN] NOVEL PROCESS FOR THE PREPARATION OF GADOLINIUM COMPLEX OF (4S)-4-(4-ETHOXYBENZYL)-3,6,9-TRIS(CARBOXYLATOMETHYL)-3,6,9- TRIAZAUNDECANEDIOIC ACID DISODIUM (GADOXETATE DISODIUM)<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE COMPLEXE DE GADOLINIUM D'ACIDE (4S)-4-(4-ÉTHOXYBENZYL) -3,6,9-TRIS (CARBOXYLATOMÉTHYL)-3,6,9-TRIAZAUNDÉCANEDIOÏQUE DISODIQUE (GADOXATE DISODIQUE)
  申请人：BIOPHORE INDIA PHARMACEUTICALS PVT LTD

  公开号：WO2017208258A1

  公开（公告）日：2017-12-07

  The present invention discloses a novel process for the preparation of gadolinium complex of (4S)-4-(4-Ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecanedioic acid disodium of formula 1 and novel intermediates thereof.

  本发明公开了一种制备化合物(4S)-4-(4-乙氧基苄基)-3,6,9-三(羧甲基)-3,6,9-三氮杂十一二酸二钠盐的钆配合物的新工艺，以及其新的中间体。
• Process for Preparing Crystalline 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic Acid and Use for Production of Primovist®
  申请人：Platzek Johannes

  公开号：US20130158241A1

  公开（公告）日：2013-06-20

  The invention relates to a method for producing crystalline 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid of the formula I by saponifying 3,6,9-triaza-3,6,9-tris(tert-butoxycarbonylmethyl)-4-(4-ethoxybenzyl)-undecanedioic acid di-tert-butyl ester of the formula II in an aqueous alkali metal hydroxide solution and using 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid of the formula I for producing the gadolinium complex of 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid [(Gd-EOB-DTPA)=Primovist®].

  本发明涉及一种制备式I晶体的方法，该方法通过在含碱金属氢氧化物水溶液中皂化式II的3,6,9-三(叔丁氧羰基甲基)-4-(4-乙氧基苯基)-十一二酸叔丁酯，然后使用式I的3,6,9-三(羧甲基)-4-(4-乙氧基苯基)-十一二酸来制备3,6,9-三(羧甲基)-4-(4-乙氧基苯基)-三嗪基-十一二酸镧配合物[(Gd-EOB-DTPA)=Primovist®]。
• NMR and chiroptical examination of the diastereoisomers of (S)-Eu–EOB–DTPA
  作者：Nicola C. Thompson、David Parker、Heribert Schmitt-Willich、Detlev Sülzle、Gilles Muller、James P. Riehl

  DOI：10.1039/b403863k

  日期：——

  The solution structure of the diastereoisomers of (S)-Eu–EOB–DTPA has been analysed by 1H NMR, CD and CPL spectroscopy. Two major species exist which possess very similar 1H NMR paramagnetic shifts and emission spectra, consistent with a 9-coordinate structure involving one bound water. Circularly polarised luminescence data are consistent with a common Λ-helicity for each isomer; the isomers differ only in the absolute configuration of the central nitrogen atom.

  通过 1H NMR、CD 和 CPL 光谱分析了 (S)-EuâEOBâDTPA 非对映异构体的溶液结构。存在两种主要的非对映异构体，它们具有非常相似的 1H NMR 顺磁位移和发射光谱，与包含一个结合水的 9 配位结构相一致。圆偏振发光数据与每种异构体的共同δ-异构体一致；异构体仅在中心氮原子的绝对构型上存在差异。
• METHOD FOR INCREASING DISPERSION STABILITY OF NANOPARTICLES AS T1 MRI CONTRAST AGENT AND T1 MRI CONTRAST AGENT NANOPARTICLES
  申请人：Industry-Academic Cooperation Foundation, Yonsei University

  公开号：EP3417882A1

  公开（公告）日：2018-12-26

  The present invention improves an existing contrast agent, especially, a T1 contrast agent, and adopts a strategy in which the T1 contrast material is partially coated on a support surface to which a hydrophilic functional group is exposed. The partial coating strategy adopted in the present invention improves both the stability and contrast performance of T1 contrast agent nanoparticles, and such a strategy leads to very interesting technical development.

  本发明改进了现有的造影剂，特别是 T1 造影剂，并采用了将 T1 造影材料部分包覆在暴露有亲水官能团的支撑表面上的策略。本发明采用的部分涂层策略既提高了 T1 造影剂纳米粒子的稳定性，又改善了其造影性能，这种策略带来了非常有趣的技术发展。
• NOVEL ANTI-HUMAN CEACAM5 ANTIBODY FAB FRAGMENT
  申请人：Astellas Pharma Inc.

  公开号：EP3650470A1

  公开（公告）日：2020-05-13

  Provided are an anti-human CEACAM5 antibody Fab fragment expected to be useful in the diagnosis of a cancer, particularly, the diagnosis of colorectal cancer, breast cancer, lung cancer, thyroid gland cancer or a cancer resulting from the metastasis thereof, and a diagnosis approach using a conjugate comprising the Fab fragment. The present invention provides an anti-human CEACAM5 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by amino acid positions 1 to 121 of SEQ ID NO: 2, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by amino acid positions 1 to 112 of SEQ ID NO: 4, and a conjugate comprising the Fab fragment.

  本发明提供了一种抗人CEACAM5抗体Fab片段，该片段有望用于癌症诊断，特别是结直肠癌、乳腺癌、肺癌、甲状腺癌或由其转移导致的癌症的诊断，以及使用包含该Fab片段的共轭物的诊断方法。本发明提供了一种抗人CEACAM5抗体Fab片段，该抗体Fab片段包括由SEQ ID NO: 2的氨基酸位置1至121所代表的氨基酸序列组成的重链可变区的重链片段和由SEQ ID NO: 4的氨基酸位置1至112所代表的氨基酸序列组成的轻链可变区的轻链，以及包含该Fab片段的共轭物。