(E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyuridine | 178179-62-9

• 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: (E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyuridine
• 英文别名: (E)-5-(2-trimethylsilylvinyl)-2'-fluoro-2'-deoxyuridine；1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione
• CAS: 178179-62-9
• 化学式: C₁₄H₂₁FN₂O₅Si
• 分子量: 344.415
• InChiKey: LXSLKOMYIJFKFZ-WLAUJBMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.02
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyuridine 在 sodium hydroxide 、 sodium iodide 、 双氧水 作用下， 以 乙醇 、 水 、 溶剂黄146 为溶剂， 生成 [123I]-(E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine
  参考文献：
  名称：

  In Vivo Evaluation of the Uptake of [123I]FIAU, [123I]IVFRU and [123I]IVFAU by Normal Mouse Brain: Potential For Noninvasive Assessment of HSV-1 Thymidine Kinase Gene Expression in Gliomas

  摘要：

  Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy--D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [124I]IVFRU and [124I]IVFAU in tumor-bearing mice are warranted.

  DOI：

  10.1080/15257770701571933
• 作为产物：
  描述：

  三丁基[(1E)-2-(三甲基硅烷基)乙烯基]锡烷 、 5-iodo-2'-deoxy-2'-fluorouridine 在 双三苯基磷二氯化钯 氩 、 silica gel 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以v/v) as eluent to yield (E)-5-(2-trimethylsilylvinyl)-2′-fluoro-2′-deoxyuridine as a white solid (146 mg, 80% yield)的产率得到(E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyuridine
  参考文献：
  名称：

  Combined use of nucleoside analogues and gene transfection for tissue imaging and therapy

  摘要：

  一种使用标记化合物监测外源基因转移的方法和用途，包括选择已从细胞或病毒中分离并转移到细胞群体中的外源基因和选择将与外源基因表达的蛋白质选择性相互作用以产生标记产物的标记化合物。标记化合物从细胞中排出的速率大于标记产物。此外，该使用和方法包括向细胞施加有效剂量的标记化合物，使标记化合物选择性地与蛋白质相互作用以产生标记产物，等待一段时间，使大量标记化合物已经排出细胞且仍有可检测量的标记产物，并通过检测标记产物确定蛋白质的程度和位置。

  公开号：

  US20020025296A1

文献信息

• Combined use of nucleoside analogues and gene transfection for tissue imaging and therapy
  申请人：——

  公开号：US20020025296A1

  公开（公告）日：2002-02-28

  A method and use of a labelled compound for monitoring the transfer of a foreign gene including selecting the foreign gene which has been isolated from a cell or virus and transferred into a cell population and selecting the labelled compound which will interact selectively with a protein expressed by the foreign gene to produce a labelled product. The labelled compound has a rate of expulsion from the cells which is greater than that of the labelled product. Further, the use and method include administering to the cells an effective dose of the labelled compound such that the labelled compound selectively interacts with the protein to produce the labelled product, waiting a period of time such that a substantial amount of the labelled compound has been expelled from the cells and such that a detectable amount of the labelled product remains and determining the extent and location of the protein by detecting the labelled product.

  一种使用标记化合物监测外源基因转移的方法和用途，包括选择已从细胞或病毒中分离并转移到细胞群体中的外源基因和选择将与外源基因表达的蛋白质选择性相互作用以产生标记产物的标记化合物。标记化合物从细胞中排出的速率大于标记产物。此外，该使用和方法包括向细胞施加有效剂量的标记化合物，使标记化合物选择性地与蛋白质相互作用以产生标记产物，等待一段时间，使大量标记化合物已经排出细胞且仍有可检测量的标记产物，并通过检测标记产物确定蛋白质的程度和位置。
• Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (<i>E</i>)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy
  作者：Kevin W. Morin、Elena D. Atrazheva、Edward E. Knaus、Leonard I. Wiebe

  DOI：10.1021/jm9606406

  日期：1997.7.1

  A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5-(2-[I-125]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)-5-(2-[I-125]Iodovinyl)-2'-deoxyuridine ([I-125]IVDU, 10), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyuridine ([I-125]IVFRU, 11), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([I-125]IVFAU, 12), and (E)-5-(2-[I-125]iodovinyl)arabinouridine ([I-125]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)-5-(2-(trimethylsilyl)vinyl) precursors (6-9) with [I-125]ICl. Cellular uptake of these labeled compounds (10-13) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.
• In Vivo Evaluation of the Uptake of [123I]FIAU, [123I]IVFRU and [123I]IVFAU by Normal Mouse Brain: Potential For Noninvasive Assessment of HSV-1 Thymidine Kinase Gene Expression in Gliomas
  作者：H. -F. Li、A. Winkeler、S. Moharram、E. E. Knaus、K. Dittmar、M. Stockle、W. D. Heiss、L. I. Wiebe、A. J. Jacob

  DOI：10.1080/15257770701571933

  日期：2008.1

  Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy--D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [124I]IVFRU and [124I]IVFAU in tumor-bearing mice are warranted.