3-{2-[5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-ylmethoxy]-2-oxo-2λ5-[1,3,2]dioxaphosphinan-4-yl}-benzoic acid methyl ester | 928780-45-4

• 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: 3-{2-[5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-ylmethoxy]-2-oxo-2λ5-[1,3,2]dioxaphosphinan-4-yl}-benzoic acid methyl ester
• CAS: 928780-45-4
• 化学式: C₃₂H₅₂N₃O₁₀PSi₂
• 分子量: 725.924
• InChiKey: WLYZJGOATZWFMY-XQASJKOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.59
• 重原子数：
  48.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  159.66
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  3-{2-[5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-ylmethoxy]-2-oxo-2λ5-[1,3,2]dioxaphosphinan-4-yl}-benzoic acid methyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以80%的产率得到5'-O-cis-[4-(3-methoxycarbonylphenyl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating > 19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and > 12-fold higher araCTP levels in the liver than in the bone marrow, representing a > 120-fold and > 28-fold improvement, respectively, over araC administration.

  DOI：

  10.1021/jm0607449
• 作为产物：
  描述：

  ethyl 3-(3-bromophenyl)-3-hydroxypropanoate 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 叔丁基氯化镁 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0~85.0 ℃ 、379.21 kPa 条件下， 反应 46.0h， 生成 3-{2-[5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-ylmethoxy]-2-oxo-2λ5-[1,3,2]dioxaphosphinan-4-yl}-benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating > 19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and > 12-fold higher araCTP levels in the liver than in the bone marrow, representing a > 120-fold and > 28-fold improvement, respectively, over araC administration.

  DOI：

  10.1021/jm0607449