1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione | 178179-66-3

• 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: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione
• CAS: 178179-66-3
• 化学式: C₁₄H₂₂N₂O₅Si
• 分子量: 326.425
• InChiKey: CSODJOQYCQMVDZ-MRPUBWEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.07
• 重原子数：
  22
• 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：
  5

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione 在 一氯化碘 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以77%的产率得到溴夫定杂质H
  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
• 作为产物：
  描述：

  碘苷 、 三丁基[(1E)-2-(三甲基硅烷基)乙烯基]锡烷 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以73%的产率得到1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-trimethylsilylethenyl]pyrimidine-2,4-dione
  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.