{1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-ethynyl-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester | 216449-56-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-ethynyl-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester
• 英文别名: pentyl N-[1-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyloxolan-2-yl]-5-ethynyl-2-oxopyrimidin-4-yl]carbamate
• CAS: 216449-56-8
• 化学式: C₂₉H₅₁N₃O₆Si₂
• 分子量: 593.911
• InChiKey: FFEZXYUOYJRCGS-HBAHCVPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.66
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-ethynyl-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 5'-deoxy-5-ethynyl-N4-(n-pentyloxycarbonyl)cytidine
  参考文献：
  名称：

  Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine

  摘要：

  A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone. (C) 2003 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)01082-x
• 作为产物：
  描述：

  5-乙炔-2,4(1h,3H-)-嘧啶二酮(9ci) 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 硫酸氢铵 、 sodium hydroxide 、 六甲基二硅氮烷 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.5h， 生成 {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-ethynyl-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester
  参考文献：
  名称：

  Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine

  摘要：

  A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone. (C) 2003 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)01082-x