4-N-octadecanoyl-2'-2'-difluoro-2'-deoxycytidine 5'-sodium phosphate | 1373932-91-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 4-N-octadecanoyl-2'-2'-difluoro-2'-deoxycytidine 5'-sodium phosphate
• CAS: 1373932-91-2
• 化学式: C₂₇H₄₅F₂N₃O₈P*Na
• 分子量: 631.63
• InChiKey: RZZLQCVPKHBDHK-MPSRYNGLSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  42.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  163.04
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  4-(N)-stearoyl gemcitabine 在 三乙胺 、 三氯氧磷 、 碳酸氢钠 、 盐酸 、 水 作用下， 以 二氯甲烷 、 甲醇 、 氯仿 为溶剂， 反应 18.0h， 以12%的产率得到4-N-octadecanoyl-2'-2'-difluoro-2'-deoxycytidine 5'-sodium phosphate
  参考文献：
  名称：

  Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles

  摘要：

  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.

  DOI：

  10.1016/j.ijpharm.2012.03.014

文献信息

• LIPOPHILIC MONOPHOSPHORYLATED DERIVATIVES AND NANOPARTICLES
  申请人：Board of Regents, The University of Texas System

  公开号：US20130131008A1

  公开（公告）日：2013-05-23

  There are provided, inter alia, lipophilic monophosphorylated derivatives of gemcitabine. There are further provided nanoparticles compositions incorporating lipophilic monophosphorylated derivatives of gemcitabine, pharmaceutical compositions thereof, and a method of treating cancer or a viral infection in a subject in need thereof, which method includes administration of a pharmaceutical composition disclosed herein.

  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。