benzyl 2-(((benzyloxy)carbonyl)amino)-3-(1,4,7,10-tetraazacyclododecan-1-yl)propanoate | 1414168-19-6

• 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: benzyl 2-(((benzyloxy)carbonyl)amino)-3-(1,4,7,10-tetraazacyclododecan-1-yl)propanoate
• CAS: 1414168-19-6
• 化学式: C₂₆H₃₇N₅O₄
• 分子量: 483.611
• InChiKey: SLVLHXGJGOOCSX-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.11
• 重原子数：
  35.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  103.96
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  benzyl 2-(((benzyloxy)carbonyl)amino)-3-(1,4,7,10-tetraazacyclododecan-1-yl)propanoate 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 20.5h， 生成 (R)-2-amino-3-(4,10-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)propanoic acid
  参考文献：
  名称：

  Probing the Structure–Relaxivity Relationship of Bis-hydrated Gd(DOTAla) Derivatives

  摘要：

  Two structural isomers of the heptadentate chelator DO3Ala were synthesized, with carboxymethyl groups at either the 1,4- or 1,7-positions of the cyclen macrocycle. To interrogate the relaxivity under different rotatational dynamics regimes, the pendant primary amine was coupled to ibuprofen to enable binding to serum albumin. These chelators 6a and 6b form bis(aqua) ternary complexes with Gd(III) or Tb(III) as estimated from relaxivity measurements or luminescence lifetime measurements in water. The relaxivity of [Gd(6a)(H2O)(2)] and [Gd(6b)(H2O)(2)] was measured in the presence and absence of coordinating anions prevalent in vivo such as phosphate, lactate, and bicarbonate and compared with data attained for the q = 2 complex [Gd(DO(3)A)(H2O)(2)]. We found that relaxivity was reduced through formation of ternary complexes with lactate and bicarbonate, albeit to a lesser degree then the relaxivity of Gd(DO(3)A). In the presence of 100-fold excess phosphate, relaxivity was slightly increased and typical for q = 2 complexes of this size (8.3 mM(-1) s1 and 9.5 mM(-1) s(-1), respectively, at 37 degrees C, 60 MHz). Relaxivity for the complexes in the presence of HSA corresponded well to relaxivity obtained for complexes with reduced access for inner-sphere water (13.5 and 12.7 mM(-1) s(-1) at 37 degrees C, 60 MHz). Mean water residency time at 37 degrees C was determined using temperature-dependent O-17-T2 measurements at 11.7 T and calculated to be (310)(tau M) = 23 +/- 1 ns for both structural isomers. Kinetic inertness under forcing conditions (pH 3, competing DTPA ligand) was found to be comparable to [Gd(DO(3)A)(H2O)]. Overall, we found that the replacement of one of the acetate arms of DO(3)A with an amino-propionate arm does not significantly alter the relaxometric and kinetic inertness properties of the corresponding Gd complexes; however, it does provide access to easily functionalizable q = 2 derivatives.

  DOI：

  10.1021/ic503035f
• 作为产物：
  描述：

  苄氧羰基-D-丝氨酸苄酯 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 17.0h， 生成 benzyl 2-(((benzyloxy)carbonyl)amino)-3-(1,4,7,10-tetraazacyclododecan-1-yl)propanoate
  参考文献：
  名称：

  Gd(DOTAla)：一种单一氨基酸 Gd 复合物作为用于高松弛性 MR 造影剂开发的模块化工具

  摘要：

  高磁场下的 MR 成像得益于更高的信噪比；然而，基于 T(1) 的 MR 造影剂在更高的场中表现出降低的弛豫率 (r(1))。可以通过仔细控制分子的旋转动力学来设计高场、高弛豫对比剂。为此，我们研究了 Gd(DOTA)、Gd(DOTAla) 的丙氨酸类似物的应用。合成了适用于固相肽合成的 Fmoc 保护的 DOTAla，并将其整合到多肽结构中。Gd(III) 配位导致金属螯合物通过氨基酸侧链和酰胺羰基的配位非常牢固地附着在肽主链上。线性和环状单体 (GdL1、GdC1)、二聚体 (Gd(2)L2、Gd(2)C2) 和三聚体 (Gd(3)L3、制备了 Gd(3)C3) 并在 0.47 至 11.7 T 的不同场强下测定弛豫度。通过测定整合到肽主链中的 EuL1 的水合数 q 间接证实了酰胺羰基配位，q = 0.96 ± 0.09 . GdL1 在 37 °C 下的水驻留时间是弛豫的最佳时间，τ(M)

  DOI：

  10.1021/ja309187m

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。