1-[(2R,4S,5R)-4-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxy]-5-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-2-yl]-5-iodopyrimidine-2,4-dione | 1313031-60-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 1-[(2R,4S,5R)-4-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxy]-5-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-2-yl]-5-iodopyrimidine-2,4-dione
• 英文别名: 1-[(2R,4S,5R)-4-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl)oxy]-5-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-2-yl]-5-iodopyrimidine-2,4-dione
• CAS: 1313031-60-5
• 化学式: C₃₉H₅₁F₂IN₂O₁₁P₂
• 分子量: 950.69
• InChiKey: WGXXPTBAWJHDIZ-HOYCACOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  57
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  5-iodo-5'-O-[cyclo-3,5-di(tert-butyl)-6-fluorosaligenyl]-3'-fluoro-2',3'-dideoxyuridine monophosphate 在 水 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.25h， 生成 5-iodo-5'-O-[cyclo-3,5-di(tert-butyl)-6-fluorosaligenyl]-2'-deoxyuridine monophosphate 、 5-iodo-3'-O-[cyclo-3,5-di-(tert-butyl)-6-fluorosaligenyl]-2'-deoxyuridine monophosphate 、 1-[(2R,4S,5R)-4-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxy]-5-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-2-yl]-5-iodopyrimidine-2,4-dione
  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