Tert-butyl 2-[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-6-[[3-[[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-6-yl]methoxycarbonylamino]-5-isothiocyanatophenyl]carbamoyloxymethyl]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-1-yl]acetate | 1256156-05-4

• 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: Tert-butyl 2-[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-6-[[3-[[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-6-yl]methoxycarbonylamino]-5-isothiocyanatophenyl]carbamoyloxymethyl]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-1-yl]acetate
• CAS: 1256156-05-4
• 化学式: C₆₉H₁₁₃N₉O₂₀S
• 分子量: 1420.77
• InChiKey: BBXGGFUGWABZTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  99
• 可旋转键数：
  43
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  351
• 氢给体数：
  2
• 氢受体数：
  28

反应信息

• 作为反应物：
  描述：

  Tert-butyl 2-[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-6-[[3-[[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-6-yl]methoxycarbonylamino]-5-isothiocyanatophenyl]carbamoyloxymethyl]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-1-yl]acetate 、 1-金刚烷甲胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到
  参考文献：
  名称：

  A new ditopic GdIII complex functionalized with an adamantyl moiety as a versatile building block for the preparation of supramolecular assemblies

  摘要：

  A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd-2 L1) able to form strong supramolecular adducts with specific hosts such as beta-cyclodextrin (beta-CD), poly-beta-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd-2 L1 were investigated in aqueous solution by measuring the H-1 relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd-2 L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM(-1) s(-1), a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5-3.0 T). The noncovalent interaction of Gd-2 L1 with beta-CD, poly-beta-CD, and HSA and the relaxometric properties of the resulting host-guest adducts were investigated using H-1 relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd-2 L1-beta-CD and Gd-2 L1-poly-beta-CD, respectively. Binding of Gd-2 L1 to HSA (K (A) = 1.2 x 10(4) M-1) results in a remarkable relaxivity of 41.4 mM(-1) s(-1) for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd-2 L1-beta-CD to Gd-2 L1-HSA. Finally, the applicability of Gd-2 L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation.

  DOI：

  10.1007/s00775-013-1050-0
• 作为产物：
  描述：

  硫光气 、 Tert-butyl 2-[6-[[3-amino-5-[[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-6-yl]methoxycarbonylamino]phenyl]carbamoyloxymethyl]-6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-1-yl]acetate 在 potassium hydrogencarbonate 作用下， 以 二氯甲烷 为溶剂， 生成 Tert-butyl 2-[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-6-[[3-[[6-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-6-yl]methoxycarbonylamino]-5-isothiocyanatophenyl]carbamoyloxymethyl]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-diazepan-1-yl]acetate
  参考文献：
  名称：

  AAZTA-based bifunctional chelating agents for the synthesis of multimeric/dendrimeric MRI contrast agents

  摘要：

  我们合成了基于 AAZTA（6-氨基-6-甲基全氢-1,4-二氮杂环四乙酸）平台的单体和二聚体双功能螯合物，该平台带有用于与生物大分子共轭的芳基氨基和异硫氰酸基。这两种体系均用于制备高松弛性树枝状（PAMAM G1）和多聚八-GdIII 复合物。由于每个金属离子上都有两个配位的、快速交换的水分子（q = 2），而且分子结构相当坚固紧凑，因此这些体系显示出更强的弛豫特性。

  DOI：

  10.1039/c0ob00096e

文献信息

• A new ditopic GdIII complex functionalized with an adamantyl moiety as a versatile building block for the preparation of supramolecular assemblies
  作者：Giuseppe Gambino、Sara De Pinto、Lorenzo Tei、Claudio Cassino、Francesca Arena、Eliana Gianolio、Mauro Botta

  DOI：10.1007/s00775-013-1050-0

  日期：2014.2

  A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd-2 L1) able to form strong supramolecular adducts with specific hosts such as beta-cyclodextrin (beta-CD), poly-beta-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd-2 L1 were investigated in aqueous solution by measuring the H-1 relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd-2 L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM(-1) s(-1), a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5-3.0 T). The noncovalent interaction of Gd-2 L1 with beta-CD, poly-beta-CD, and HSA and the relaxometric properties of the resulting host-guest adducts were investigated using H-1 relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd-2 L1-beta-CD and Gd-2 L1-poly-beta-CD, respectively. Binding of Gd-2 L1 to HSA (K (A) = 1.2 x 10(4) M-1) results in a remarkable relaxivity of 41.4 mM(-1) s(-1) for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd-2 L1-beta-CD to Gd-2 L1-HSA. Finally, the applicability of Gd-2 L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation.
• AAZTA-based bifunctional chelating agents for the synthesis of multimeric/dendrimeric MRI contrast agents
  作者：Giuseppe Gugliotta、Mauro Botta、Lorenzo Tei

  DOI：10.1039/c0ob00096e

  日期：——

  Monomeric and dimeric bifunctional chelates based on the AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) platform bearing arylamino and isothiocyanate groups for conjugation to biomolecules were synthesised. Both systems were used for the preparation of high relaxivity dendrimeric (PAMAM G1) and multimeric octa-GdIII complexes. These systems show enhanced relaxometric properties attributed to the presence of two coordinated, fast exchanging, water molecules (q = 2) on each metal ion and to a rather rigid and compact molecular structure.

  我们合成了基于 AAZTA（6-氨基-6-甲基全氢-1,4-二氮杂环四乙酸）平台的单体和二聚体双功能螯合物，该平台带有用于与生物大分子共轭的芳基氨基和异硫氰酸基。这两种体系均用于制备高松弛性树枝状（PAMAM G1）和多聚八-GdIII 复合物。由于每个金属离子上都有两个配位的、快速交换的水分子（q = 2），而且分子结构相当坚固紧凑，因此这些体系显示出更强的弛豫特性。