(E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyarabino-uridine | 178179-64-1

• 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'-deoxyarabino-uridine
• 英文别名: 1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione
• CAS: 178179-64-1
• 化学式: C₁₄H₂₁FN₂O₅Si
• 分子量: 344.415
• InChiKey: LXSLKOMYIJFKFZ-NTMZSYSQSA-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'-deoxyarabino-uridine 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'-deoxyarabino-uridine
  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 、 非阿尿苷 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以64%的产率得到(E)-5-(2-(trimethylsilyl)vinyl)-2'-fluoro-2'-deoxyarabino-uridine
  参考文献：
  名称：

  Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-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

  摘要：

  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.

  DOI：

  10.1021/jm9606406

文献信息

• 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.