3’-脱氧-3’-氟-5’-O-(4,4’-二甲氧基三苯甲基)胸苷 | 290371-78-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 3’-脱氧-3’-氟-5’-O-(4,4’-二甲氧基三苯甲基)胸苷
• 英文名称: 5'-O-(4,4'-dimethoxytrityl)-3'-deoxy-3'-fluorothymidine
• 英文别名: 3'-Deoxy-3'-fluoro-5'-O-(4,4'-dimethoxytrityl)thymidine；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-fluorooxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 290371-78-7
• 化学式: C₃₁H₃₁FN₂O₆
• 分子量: 546.595
• InChiKey: DYWGIYQONVUVCS-UPRLRBBYSA-N

物化性质

• 熔点：
  88 °C
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  二氯甲烷，

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3’-脱氧-3’-氟-5’-O-(4,4’-二甲氧基三苯甲基)胸苷 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 3’-脱氧-3-氟胸苷
  参考文献：
  名称：

  Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents

  摘要：

  本文披露了包含正电子发射体或伽马辐射放射性卤化物的某些环丝氨基嘧啶核苷酸单磷酸盐，其用于监测阿尔茨海默病的进展并评估对治疗的反应，以及它们的制备过程。

  公开号：

  US20090117041A1
• 作为产物：
  描述：

  保护胸苷 在 吡啶 、 二乙胺基三氟化硫 、 甲基磺酰氯 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 3’-脱氧-3’-氟-5’-O-(4,4’-二甲氧基三苯甲基)胸苷
  参考文献：
  名称：

  Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation

  摘要：

  Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. 1050 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

  DOI：

  10.1021/jm201482p

文献信息

• Synthesis of 3′‐deoxy‐3′‐[ ¹⁸ F]fluoro‐thymidine with 2,3′‐anhydro‐5′‐ <i>O</i> ‐(4,4′‐dimethoxytrityl)‐thymidine
  作者：C. Wodarski、J. Eisenbarth、K. Weber、M. Henze、U. Haberkorn、M. Eisenhut

  DOI：10.1002/1099-1344(20001030)43:12<1211::aid-jlcr408>3.0.co;2-#

  日期：2000.10.30

  [C-11]Thymidine has been used as a proliferation marker in positron-emission-tomography (PET) studies of tumors. This compound showed metabolite related problems and the radiosynthesis proved to be difficult. Recently, the more stable 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) has been suggested as an alternative. One advantage of [F-18]FLT is based on thymidine kinase-1 catalyzed phosphorylation of FLT and the intracellular accumulation of this metabolite without participation in DNA synthesis. The radiosynthesis of [F-18]FLT originally designed by Grierson et al. was found to be demanding especially regarding the workup df the [F-18]fluoride/1-(2-deoxy-3 -O-nosyl-5-O-DMT-beta -D-threo-pento-furanosyl)-3-DMBn-thymine reaction mixture. Instead, we us ed 2,3'-anhydro-5'-0-(4,4'-dimethoxytrityl) thymi dine as a precursor for the synthesis of [F-18]FLT. In DMSO at 175 degreesC and in presence of Kryptofix(R) 2.2.2. we obtained 5.6+/-1,4 % [F-18]FLT (EOS).
• Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents
  申请人：Kortylewicz Zbigniew P.

  公开号：US20090117041A1

  公开（公告）日：2009-05-07

  Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

  本文披露了包含正电子发射体或伽马辐射放射性卤化物的某些环丝氨基嘧啶核苷酸单磷酸盐，其用于监测阿尔茨海默病的进展并评估对治疗的反应，以及它们的制备过程。
• Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation
  作者：Zbigniew P. Kortylewicz、Yu Kimura、Kotaro Inoue、Elizabeth Mack、Janina Baranowska-Kortylewicz

  DOI：10.1021/jm201482p

  日期：2012.3.22

  Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. 1050 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.