1,4,7-tris(carboxymethyl)-10-(2-hydroxybutyl)-1,4,7,10-tetraazacyclododecane

• 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: 1,4,7-tris(carboxymethyl)-10-(2-hydroxybutyl)-1,4,7,10-tetraazacyclododecane
• 英文别名: 2-[4,7-Bis(carboxymethyl)-10-(2-hydroxybutyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• 化学式: C₁₈H₃₄N₄O₇
• 分子量: 418.491
• InChiKey: SFUNJHUDWCYRBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  gadolinium(III) chloride hexahydrate 、 1,4,7-tris(carboxymethyl)-10-(2-hydroxybutyl)-1,4,7,10-tetraazacyclododecane 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  大环钆基 MR 造影剂与 I 型胶原蛋白的相互作用。平衡和动力学研究

  摘要：

  通过超滤和透析研究钆酸葡甲胺、钆布醇、钆特醇和 Gd(HB-DO3A) 与牛 I 型胶原的相互作用。四种药物对胶原蛋白的亲和力相似。然而，Gd III-复合物的最大吸附量按以下顺序减少：钆酸葡甲胺>钆布醇>钆特醇>Gd(HB-DO3A)。用开放式三室模型计算表明，结构同系物钆和 Gd(HB-DO3A) 对胶原蛋白的吸附较低，这可能解释了在大鼠软组织中观察到的钆多醇在体内保留时间较短的原因。

  DOI：

  10.1039/d0dt03314f
• 作为产物：
  描述：

  1,4,7,10-tetraazatricyclo[5.5.1.0^4,13]tridecane 在 sodium hydroxide 、 水 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 35.0h， 生成 1,4,7-tris(carboxymethyl)-10-(2-hydroxybutyl)-1,4,7,10-tetraazacyclododecane
  参考文献：
  名称：

  Glogard, Christian; Hovland, Ragnar; Fossheim, Sigrid L., Journal of the Chemical Society. Perkin Transactions 2 (2001), 2000, # 5, p. 1047 - 1052

  摘要：

  DOI：

文献信息

• Dimeric contrast agents
  申请人：BRACCO IMAGING S.P.A.

  公开号：US10793533B2

  公开（公告）日：2020-10-06

  The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with the paramagnetic metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.

  本发明涉及能够螯合顺磁性金属离子的新型二聚大环、它们与顺磁性金属离子的螯合络合物及其作为造影剂的用途，尤其适用于磁共振成像（MRI）分析。
• DIMERIC CONTRAST AGENTS
  申请人：BRACCO IMAGING S.P.A.

  公开号：US20200017453A1

  公开（公告）日：2020-01-16

  The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with the paramagnetic metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
• NOVEL PROCESS FOR THE PREPARATION OF MACROCYCLIC CHELANT 2,2',2''-(10-(2-HYDROXYPROPYL)-1,4,7,10-TETRA AZACYCLODODECANE-1,4,7-TRIYL) TRIACETIC ACID AND IT'S COMPLEXES WITH PARAMAGNETIC METAL IONS
  申请人：BIOPHORE INDIA PHARMACEUTICALS PVT. LTD

  公开号：US20210380542A1

  公开（公告）日：2021-12-09

  The present invention relates to an improved process for the preparation of macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to the process for the preparation of metal complexes of macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1) with purity greater than 99.0% by HPLC. The present invention also relates to an improved process for the preparation of gadolinium complex of formula (1a) with macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to a novel process for the preparation of calcium complex of formula (1b) with macrocyclic chelant 2,2′,2″-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1).
• [EN] DIMERIC CONTRAST AGENTS<br/>[FR] AGENTS DE CONTRASTE DIMÉRIQUES
  申请人：BRACCO IMAGING SPA

  公开号：WO2018108780A1

  公开（公告）日：2018-06-21

  The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with the paramagnetic metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
• [Gd(HB‐DO3A)]: Equilibrium, Dissociation Kinetic and Structural Differences in a Simple Homolog of [Gd(HP‐DO3A)] (Prohance^®)
  作者：Silvia Versolatto、Mariangela Boccalon、Nicol Guidolin、Fabio Travagin、Enzo Alessio、Silvio Aime、Gabriele Balducci、Giovanni B. Giovenzana、Zsolt Baranyai

  DOI：10.1002/chem.202400344

  日期：——

  [Gd(HP‐DO3A)] (gadoteridol) as an active compound of ProHance^® is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long‐term retention of gadolinium‐based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP‐DO3A)]. It was deemed of interest to assess how minor structural/electronic changes associated to the ligand structure may affect basic properties of the metal complex with several [Gd(HP‐DO3A)] analogues synthesized and characterized in the last years. We recently reported that the closest homolog of [Gd(HP‐DO3A)], i. e.: [Gd(HB‐DO3A)], in which a (±)‐2‐hydroxy‐1‐propyl pendant arm is replaced by a (±)‐2‐hydroxy‐1‐butyl moiety, showed a significantly different retention behaviour in the model interaction with collagen, despite the apparently very minor structural difference. In this paper we report a comprehensive study of the structural, thermodynamic, kinetic and relaxation properties of [Gd(HB‐DO3A)], compared to the parent [Gd(HP‐DO3A)] and to other closely related macrocyclic GBCAs to assess whether very minor structural changes can modulate the physico‐chemical properties of Gd³⁺ complexes.