5-(((2R,3R,5R)-5-(4-((tert-butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-2-(((tert-butoxycarbonyl)oxy)methyl)-4,4-difluorotetrahydrofuran-3-yl)oxy)-5-oxopentanoic acid | 1589598-08-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-(((2R,3R,5R)-5-(4-((tert-butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-2-(((tert-butoxycarbonyl)oxy)methyl)-4,4-difluorotetrahydrofuran-3-yl)oxy)-5-oxopentanoic acid
• CAS: 1589598-08-2
• 化学式: C₂₄H₃₃F₂N₃O₁₁
• 分子量: 577.536
• InChiKey: ULSCOXAYCTXPJA-FSPWUOQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  40.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  181.58
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  戊二酸酐 、 4-N-5'-O-bis(tert-butoxycarbonyl)gemcitabine 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 5-(((2R,3R,5R)-5-(4-((tert-butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-2-(((tert-butoxycarbonyl)oxy)methyl)-4,4-difluorotetrahydrofuran-3-yl)oxy)-5-oxopentanoic acid
  参考文献：
  名称：

  GnRH-Gemcitabine Conjugates for the Treatment of Androgen-Independent Prostate Cancer: Pharmacokinetic Enhancements Combined with Targeted Drug Delivery

  摘要：

  Gemcitabine, a drug with established efficacy against a number of solid tumors, has therapeutic limitations due to its rapid metabolic inactivation. The aim of this study was the development of an innovative strategy to produce a metabolically stable analogue of gemcitabine that could also be selectively delivered to prostate cancer (CaP) cells based on cell surface expression of the Gonadotropin Releasing Hormone-Receptor (GnRH-R). The synthesis and evaluation of conjugated molecules, consisting of gemcitabine linked to a GnRH agonist, is presented along with results in androgen-independent prostate cancer models. NMR and ligand binding assays were employed to verify conservation of microenvironments responsible for binding of novel GnRH-gemcitabine conjugates to the GnRH-R. In vitro cytotoxicity, cellular uptake, and metabolite formation of the conjugates were examined in CaP cell lines. Selected conjugates were efficacious in the in vitro assays with one of them, namely, GSG, displaying high antiproliferative activity in CaP cell lines along with significant metabolic and pharmacokinetic advantages in comparison to gemcitabine. Finally, treatment of GnRH-R positive xenografted mice with GSG showed a significant advantage in tumor growth inhibition when compared to gemcitabine.

  DOI：

  10.1021/bc500081g