3-(10-bromodecanyl)-3',5'-bis-O-(tert-butyldimethylsilanyl)thymidine | 1073341-71-5

• 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-(10-bromodecanyl)-3',5'-bis-O-(tert-butyldimethylsilanyl)thymidine
• 英文别名: 3-(10-bromodecyl)-1-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1073341-71-5
• 化学式: C₃₂H₆₁BrN₂O₅Si₂
• 分子量: 689.922
• InChiKey: TXYPWBNUJKPGIL-UPRLRBBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.53
• 重原子数：
  42
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(10-bromodecanyl)-3',5'-bis-O-(tert-butyldimethylsilanyl)thymidine 、 N-[(tert-butoxy)carbonyl]-L-cysteine methyl ester 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以93%的产率得到3-{10-[S-(N-Boc-cysteine methyl ester)]decyl}-3',5'-bis-O-(tert-butyldimethylsilanyl)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：

  1,10-二溴癸烷 、 3,5-双-o-(t-丁基二甲基甲硅烷基)胸腺嘧啶脱氧核苷 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以82%的产率得到3-(10-bromodecanyl)-3',5'-bis-O-(tert-butyldimethylsilanyl)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.