11-[bis(carboxymethyl)amino]undecanoic acid | 550312-74-8

• 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: 11-[bis(carboxymethyl)amino]undecanoic acid
• 英文别名: 11-[bis(2-methoxy-2-oxoethyl)amino]undecanoic acid
• CAS: 550312-74-8
• 化学式: C₁₇H₃₁NO₆
• 分子量: 345.436
• InChiKey: LBLVLNSGHCLHBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  24.0
• 可旋转键数：
  15.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  93.14
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  11-[bis(carboxymethyl)amino]undecanoic acid 在 sodium hydroxide 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Synthesis, in vitro and in silico assessment of organometallic Rhenium(I) and Technetium(I) thymidine complexes

  摘要：

  Thymidine kinases have been identified as suitable targets for non-invasive imaging of gene therapy and cancer. Thus, there is a high interest in new, reliable and inexpensive radiolabeled thymidine analogues for these applications. In this study we present the synthesis and in vitro evaluation of M(CO)(3)-complexes of thymidine (M = Tc-99m, Re) for potential use in SPECT tumor imaging. 5'-amino-5'-deoxythymidine was derivatized at position C5' with spacers of various lengths (similar to 0-30 angstrom) carrying tridentate metal chelating entities such as iminodiacetic acid and picolylamine-N-monoacetic acid. The nucleoside derivatives were reacted with the precursors [ReBr3(CO)(3)](2-) and [Tc-99m(OH2)(3)(CO)(3)](+), respectively. The organometallic thymidine complexes have been fully characterized by means of IR, NMR and mass spectrometry. Enzyme kinetic studies revealed mixed inhibition of the human cytosolic thymidine kinase with K-i values ranging from 4.4 to 334 mu M for all thymidine complexes. Competitive inhibition of herpes simplex virus type 1 thymidine kinase was only achieved when thymidine and the metal core were separated by a spacer of approximately 30 angstrom length. These findings were supported by in silico molecular docking and molecular dynamic experiments. (C) 2006 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2006.08.101
• 作为产物：
  描述：

  11-氨基十一酸 、 溴乙酸甲酯 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以48%的产率得到11-[bis(carboxymethyl)amino]undecanoic acid
  参考文献：
  名称：

  Synthesis, in vitro and in silico assessment of organometallic Rhenium(I) and Technetium(I) thymidine complexes

  摘要：

  Thymidine kinases have been identified as suitable targets for non-invasive imaging of gene therapy and cancer. Thus, there is a high interest in new, reliable and inexpensive radiolabeled thymidine analogues for these applications. In this study we present the synthesis and in vitro evaluation of M(CO)(3)-complexes of thymidine (M = Tc-99m, Re) for potential use in SPECT tumor imaging. 5'-amino-5'-deoxythymidine was derivatized at position C5' with spacers of various lengths (similar to 0-30 angstrom) carrying tridentate metal chelating entities such as iminodiacetic acid and picolylamine-N-monoacetic acid. The nucleoside derivatives were reacted with the precursors [ReBr3(CO)(3)](2-) and [Tc-99m(OH2)(3)(CO)(3)](+), respectively. The organometallic thymidine complexes have been fully characterized by means of IR, NMR and mass spectrometry. Enzyme kinetic studies revealed mixed inhibition of the human cytosolic thymidine kinase with K-i values ranging from 4.4 to 334 mu M for all thymidine complexes. Competitive inhibition of herpes simplex virus type 1 thymidine kinase was only achieved when thymidine and the metal core were separated by a spacer of approximately 30 angstrom length. These findings were supported by in silico molecular docking and molecular dynamic experiments. (C) 2006 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2006.08.101

文献信息

• First organometallic inhibitors for human thymidine kinase: synthesis and in vitro evaluation of rhenium(I)- and technetium(I)-tricarbonyl complexes of thymidine
  作者：R. Schibli、M. Netter、L. Scapozza、M. Birringer、P. Schelling、C. Dumas、J. Schoch、P.A. Schubiger

  DOI：10.1016/s0022-328x(02)02100-9

  日期：2003.2

  unspecific interaction with other functional groups of the pharmacophor. The organometallic rhenium–nucleoside complexes have been tested in vitro for competitive inhibition of human cytosolic thymidine kinase (hTK1) and herpes simplex virus thymidine kinase type 1 (HSV1-TK). In case of hTK1 it could be observed, that the inhibition capacity of the complexes improved with increasing spacer length.

  已经合成了六种5'-氨基胸苷的5'-羧酰胺衍生物，它们具有各种长度的烷基链和三齿亚氨基二乙酸基螯合体系。胸苷类似物已与前体fac- [M（H 2 O）3（CO）3 ] +（M = 99m Tc，Re）在水性介质中反应，以良好的产率形成水溶性和稳定的有机金属配合物。1个1 H-NMR和IR光谱分析在所有情况下均仅通过三齿螯合物证实了金属-三羰基片段的三齿络合物，并且没有与药效基团的其他官能团发生非特异性相互作用。已对有机金属rh-核苷复合物进行了体外竞争性抑制人胞浆胸苷激酶（hTK1）和1型单纯疱疹病毒胸苷激酶（HSV1-TK）的测试。在hTK1的情况下，可以观察到，复合物的抑制能力随着间隔物长度的增加而提高。另一方面，所有六个复合物均未显示或仅轻微抑制了HSV1-TK。制备了相应的放射性tech 99m配合物，并在生理磷酸盐缓冲液和人血清白蛋白中于37°C进行了24小时的稳定性挑战。