[(2R,3R,4R,5R)-4-acetyloxy-5-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate | 573671-37-1

• 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: [(2R,3R,4R,5R)-4-acetyloxy-5-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate
• CAS: 573671-37-1
• 化学式: C₁₅H₁₆N₂O₇
• 分子量: 336.301
• InChiKey: KFOLUFHQLWDQFV-UBPLGANQSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-4-acetyloxy-5-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 sodium hydroxide 、 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 27.5h， 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
• 作为产物：
  描述：

  三-o-乙酰基-5-脱氧-d-呋喃核糖 、 5-乙炔-2,4(1h,3H-)-嘧啶二酮(9ci) 在 硫酸氢铵 、 六甲基二硅氮烷 、 四氯化锡 作用下， 以 硝基甲烷 、 乙腈 为溶剂， 反应 7.0h， 以64%的产率得到[(2R,3R,4R,5R)-4-acetyloxy-5-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate
  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

文献信息

• 5'-Deoxy-cytidine derivatives
  申请人：F. Hoffmann-La Roche AG

  公开号：EP0882734B1

  公开（公告）日：2009-08-26
• US6114520A
  申请人：——

  公开号：US6114520A

  公开（公告）日：2000-09-05
• US6211166B1
  申请人：——

  公开号：US6211166B1

  公开（公告）日：2001-04-03