tri-­tert-­butyl 2,2',2''-(10-­(2-­((((9H-­fluoren-­9-­yl)methoxy)carbonyl)amino)-­3-­oxo-­3-­((­1-­phenylethyl)amino)propyl)-­1,4,7,10-tetraazacyclododecane-­1,4,7-­triyl)triacetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: tri-­tert-­butyl 2,2',2''-(10-­(2-­((((9H-­fluoren-­9-­yl)methoxy)carbonyl)amino)-­3-­oxo-­3-­((­1-­phenylethyl)amino)propyl)-­1,4,7,10-tetraazacyclododecane-­1,4,7-­triyl)triacetate
• 英文别名: tert-butyl 2-[4-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-oxo-3-[[(1R)-1-phenylethyl]amino]propyl]-7,10-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetate
• 化学式: C₅₂H₇₄N₆O₉
• 分子量: 927.194
• InChiKey: UWHCYKDAYXOVHO-AWSVAJQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  67
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  tri-­tert-­butyl 2,2',2''-(10-­(2-­((((9H-­fluoren-­9-­yl)methoxy)carbonyl)amino)-­3-­oxo-­3-­((­1-­phenylethyl)amino)propyl)-­1,4,7,10-tetraazacyclododecane-­1,4,7-­triyl)triacetate 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.08h， 生成 tri-­tert-butyl 2,2',2''-(10-­(2-­(2-­((((9H-­fluoren-9-yl)methoxy)carbonyl)amino)-3-­(4-hydroxy-­3,5-­diiodophenyl)propanamido)-­3-oxo-­3-((-1-phenylethyl)amino)propyl)-1,4,7,10-­tetraazacyclododecane-1,4,7-­triyl)triacetate
  参考文献：
  名称：

  Structure–Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex

  摘要：

  The Gd(III) complex of DO3A-N-alpha-aminopropionate, Gd(DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA). Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA. Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity

  DOI：

  10.1021/jm4000177
• 作为产物：
  描述：

  (S)-(-)- α-甲基苄胺 、 2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]propanoic acid 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.08h， 生成 tri-­tert-­butyl 2,2',2''-(10-­(2-­((((9H-­fluoren-­9-­yl)methoxy)carbonyl)amino)-­3-­oxo-­3-­((­1-­phenylethyl)amino)propyl)-­1,4,7,10-tetraazacyclododecane-­1,4,7-­triyl)triacetate
  参考文献：
  名称：

  Structure–Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex

  摘要：

  The Gd(III) complex of DO3A-N-alpha-aminopropionate, Gd(DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA). Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA. Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity

  DOI：

  10.1021/jm4000177

文献信息

• [EN] PEPTIDIC STRUCTURES INCORPORATING AN AMINO ACID METAL COMPLEX AND APPLICATIONS IN MAGNETIC RESONANCE IMAGING<br/>[FR] STRUCTURES PEPTIDIQUES INCORPORANT UN COMPLEXE ACIDE AMINÉ-MÉTAL ET APPLICATIONS EN IMAGERIE À RÉSONANCE MAGNÉTIQUE
  申请人：GEN HOSPITAL CORP

  公开号：WO2014075079A1

  公开（公告）日：2014-05-15

  A method for increasing the relaxivity of a contrast agent having a metal ion complexed to a chelator is disclosed. The metal ion complex is tethered to the remainder of the molecule by at least two points of attachment such that local motion is limited and higher relaxivity can be achieved. In one non-limiting example version of the invention, the alanine analogue of Gd(DOTA), Gd(DOTAIa) wherein Gd is gadolinium and DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was integrated into polypeptide structures. This resulted in very rigid attachment of the metal ion complex to the peptide backbone. Rigid molecular structures provide fewer degrees of rotational freedom, resulting in greater control over the rotational dynamics and resultant relaxivity. In the case of Gd(DOTAIa), the metal complex is tethered to the peptide via the amino acid side chain to the DOTA moiety and via a dative bond from an amide oxygen to the Gd(lll) ion.

  揭示了一种增加对比剂弛豫率的方法，该对比剂具有与螯合剂络合的金属离子。金属离子络合物通过至少两个连接点与分子的其余部分相连，从而限制局部运动并实现更高的弛豫率。在发明的一个非限制性示例版本中，将Gd(DOTA)的丙氨酸类似物Gd(DOTAIa)（其中Gd为钆，DOTA为1,4,7,10-四氮杂环十二酸-1,4,7,10-四乙酸）整合到多肽结构中。这导致金属离子复合物与肽骨架的非常刚性连接。刚性分子结构提供较少的旋转自由度，从而更好地控制旋转动力学和结果弛豫率。在Gd(DOTAIa)的情况下，金属络合物通过氨基酸侧链与DOTA基团相连，并通过酰胺氧原子与Gd(lll)离子之间的配位键相连。
• PEPTIDIC STRUCTURES INCORPORATING AN AMINO ACID METAL COMPLEX AND APPLICATIONS IN MAGNETIC RESONANCE IMAGING
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US20150297761A1

  公开（公告）日：2015-10-22

  A method for increasing the relaxivity of a contrast agent having a metal ion complexed to a chelator is disclosed. The metal ion complex is tethered to the remainder of the molecule by at least two points of attachment such that local motion is limited and higher relaxivity can be achieved. In one non-limiting example version of the invention, the alanine analogue of Gd(DOTA), Gd(DOTAla) wherein Gd is gadolinium and DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was integrated into polypeptide structures. This resulted in very rigid attachment of the metal ion complex to the peptide backbone. Rigid molecular structures provide fewer degrees of rotational freedom, resulting in greater control over the rotational dynamics and resultant relaxivity. In the case of Gd(DOTAla), the metal complex is tethered to the peptide via the amino acid side chain to the DOTA moiety and via a dative bond from an amide oxygen to the Gd(III) ion.

  本发明揭示了一种增加金属离子与螯合剂配合物的弛豫度的方法。金属离子复合物通过至少两个连接点与分子的其余部分相连，从而限制局部运动，从而可以实现更高的弛豫度。在本发明的一个非限制性示例版本中，将Gd(DOTA)的丙氨酸类似物，Gd(DOTAla)（其中Gd是钆，DOTA是1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸）整合到多肽结构中。这导致金属离子复合物与肽骨架之间非常严格的连接。刚性分子结构提供较少的旋转自由度，从而实现对旋转动力学和弛豫度的更好控制。在Gd(DOTAla)的情况下，金属配合物通过氨基酸侧链与DOTA基团相连，并通过酰胺氧原子与Gd（III）离子形成配位键。
• Structure–Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex
  作者：Eszter Boros、Peter Caravan

  DOI：10.1021/jm4000177

  日期：2013.2.28

  The Gd(III) complex of DO3A-N-alpha-aminopropionate, Gd(DOTAla), was used to generate a small library of putative MRI probes targeted to human serum albumin (HSA). Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA. Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity