3-[N,N-bis-(O-methylcarboxymethyl)aminoethyl]thymidine | 1073341-79-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3-[N,N-bis-(O-methylcarboxymethyl)aminoethyl]thymidine
• 英文别名: methyl 2-[2-[3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]ethyl-(2-methoxy-2-oxoethyl)amino]acetate
• CAS: 1073341-79-3
• 化学式: C₁₈H₂₇N₃O₉
• 分子量: 429.427
• InChiKey: NQNYHVOHWCZWOK-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-[N,N-bis-(O-methylcarboxymethyl)aminoethyl]thymidine 在 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 以68%的产率得到3-[2-[bis(carboxymethyl)amino]ethyl]thymidine
  参考文献：
  名称：

  Synthesis, In Vitro, and In Silico Evaluation of Organometallic Technetium and Rhenium Thymidine Complexes with Retained Substrate Activity toward Human Thymidine Kinase Type 1

  摘要：

  Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for noninvasive imaging of cancer cell proliferation using radiolabeled substrates such as [F-18]fluorothymidine ([F-18]FLT). However, a thymidine tracer useful for single photon emission tomography (SPECT) based off the inexpensive radionuclide technetium-99m would be of significant interest. In this work, a series of thymidine derivatives labeled with the organometallic [M(CO)(3)](+) core (M = Tc-99m, Re) were synthesized. Neutral, cationic, and anionic complexes were readily formed in aqueous media. and all were substrates of recombinant hTK1 when incubated with ATP. The neutral complexes were phosphorylated to a greater extent than the charged complexes. The extent of phosphorylation was further improved by increasing the spacer length separating thymidine and the organometallic core. A molecular dynamics Simulation Study performed with a modified hTK1 structure Supported the experimental findings. In vitro cell internalization experiments performed if) a human neuroblastoma cell line (SKNMC) showed low uptake of the charged complexes but significant uptake for the neutral, lipophilic complexes with a log P value > 1.

  DOI：

  10.1021/jm800530p
• 作为产物：
  描述：

  溴乙酸甲酯 、 3-(2-aminoethyl)thymidine 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以90%的产率得到3-[N,N-bis-(O-methylcarboxymethyl)aminoethyl]thymidine
  参考文献：
  名称：

  Synthesis, In Vitro, and In Silico Evaluation of Organometallic Technetium and Rhenium Thymidine Complexes with Retained Substrate Activity toward Human Thymidine Kinase Type 1

  摘要：

  Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for noninvasive imaging of cancer cell proliferation using radiolabeled substrates such as [F-18]fluorothymidine ([F-18]FLT). However, a thymidine tracer useful for single photon emission tomography (SPECT) based off the inexpensive radionuclide technetium-99m would be of significant interest. In this work, a series of thymidine derivatives labeled with the organometallic [M(CO)(3)](+) core (M = Tc-99m, Re) were synthesized. Neutral, cationic, and anionic complexes were readily formed in aqueous media. and all were substrates of recombinant hTK1 when incubated with ATP. The neutral complexes were phosphorylated to a greater extent than the charged complexes. The extent of phosphorylation was further improved by increasing the spacer length separating thymidine and the organometallic core. A molecular dynamics Simulation Study performed with a modified hTK1 structure Supported the experimental findings. In vitro cell internalization experiments performed if) a human neuroblastoma cell line (SKNMC) showed low uptake of the charged complexes but significant uptake for the neutral, lipophilic complexes with a log P value > 1.

  DOI：

  10.1021/jm800530p

文献信息

• Synthesis, In Vitro, and In Silico Evaluation of Organometallic Technetium and Rhenium Thymidine Complexes with Retained Substrate Activity toward Human Thymidine Kinase Type 1
  作者：Dominique Desbouis、Harriet Struthers、Vojtech Spiwok、Tatiana Küster、Roger Schibli

  DOI：10.1021/jm800530p

  日期：2008.11.13

  Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for noninvasive imaging of cancer cell proliferation using radiolabeled substrates such as [F-18]fluorothymidine ([F-18]FLT). However, a thymidine tracer useful for single photon emission tomography (SPECT) based off the inexpensive radionuclide technetium-99m would be of significant interest. In this work, a series of thymidine derivatives labeled with the organometallic [M(CO)(3)](+) core (M = Tc-99m, Re) were synthesized. Neutral, cationic, and anionic complexes were readily formed in aqueous media. and all were substrates of recombinant hTK1 when incubated with ATP. The neutral complexes were phosphorylated to a greater extent than the charged complexes. The extent of phosphorylation was further improved by increasing the spacer length separating thymidine and the organometallic core. A molecular dynamics Simulation Study performed with a modified hTK1 structure Supported the experimental findings. In vitro cell internalization experiments performed if) a human neuroblastoma cell line (SKNMC) showed low uptake of the charged complexes but significant uptake for the neutral, lipophilic complexes with a log P value > 1.