4-N-3'-O-bis(tert-butoxycarbonyl)-2'-2'-difluoro-cytidine-5'-octadecylphosphate | 1373932-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-N-3'-O-bis(tert-butoxycarbonyl)-2'-2'-difluoro-cytidine-5'-octadecylphosphate
• CAS: 1373932-86-5
• 化学式: C₃₇H₆₄F₂N₃O₁₁P
• 分子量: 795.899
• InChiKey: JFZSGBZGJHUMDY-JJEZKPMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.84
• 重原子数：
  54.0
• 可旋转键数：
  24.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  173.74
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  4-N-3'-O-bis(tert-butoxycarbonyl)-2'-2'-difluoro-cytidine-5'-octadecylphosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以58%的产率得到2'-2'-difluoro-deoxycytidine-5'-octadecylphosphate
  参考文献：
  名称：

  LIPOPHILIC MONOPHOSPHORYLATED DERIVATIVES AND NANOPARTICLES

  摘要：

  其中提供了伊立替宾的亲脂性单磷酸化衍生物，还提供了包含伊立替宾的亲脂性单磷酸化衍生物的纳米粒子组合物、相应的药物组合物，以及一种治疗癌症或病毒感染的方法，该方法包括给需要的受试者使用本文披露的药物组合物。

  公开号：

  US20130131008A1
• 作为产物：
  描述：

  盐酸吉西他滨 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 159.0h， 生成 4-N-3'-O-bis(tert-butoxycarbonyl)-2'-2'-difluoro-cytidine-5'-octadecylphosphate
  参考文献：
  名称：

  LIPOPHILIC MONOPHOSPHORYLATED DERIVATIVES AND NANOPARTICLES

  摘要：

  其中提供了伊立替宾的亲脂性单磷酸化衍生物，还提供了包含伊立替宾的亲脂性单磷酸化衍生物的纳米粒子组合物、相应的药物组合物，以及一种治疗癌症或病毒感染的方法，该方法包括给需要的受试者使用本文披露的药物组合物。

  公开号：

  US20130131008A1

文献信息

• Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles
  作者：Dharmika S.P. Lansakara-P.、B. Leticia Rodriguez、Zhengrong Cui

  DOI：10.1016/j.ijpharm.2012.03.014

  日期：2012.6

  Gemcitabine hydrochloride (HCl) is approved for the treatment of a wide spectrum of solid tumors. However, the rapid development of resistance often makes gemcitabine less efficacious. In the present study, we synthesized several novel lipophilic monophosphorylated gemcitabine derivatives, incorporated them into solid lipid nanoparticles, and then evaluated their ability to overcome major known gemcitabine resistance mechanisms by evaluating their in vitro cytotoxicities in cancer cells that are deficient in deoxycytidine kinase (dCK), deficient in human equilibrative nucleoside transporter (hENT1), over-expressing ribonucleotide reductase M1 subunit (RRM1), or over-expressing RRM2. In dCK deficient cells, the monophosphorylated gemcitabine derivatives and their nanoparticles were up to 86-fold more cytotoxic than gemcitabine HCl. The majority of the gemcitabine derivatives and their nanoparticles were more cytotoxic than gemcitabine HCl in cells that over-expressing RRM1 or RRM2, and the gemcitabine derivatives in nanoparticles were also resistant to deamination by deoxycytidine deaminase. The gemcitabine derivatives (in nanoparticles) hold a great potential in overcoming gemcitabine resistance. (c) 2012 Elsevier B.V. All rights reserved.