3-(5'-fluoro-3'H-2',4'-pyridinediketone)-3-oxo propionic acid | 871682-14-3

• 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: 3-(5'-fluoro-3'H-2',4'-pyridinediketone)-3-oxo propionic acid
• 英文别名: 3-(5-Fluoro-2,4-dioxopyrimidin-1-yl)-3-oxopropanoic acid
• CAS: 871682-14-3
• 化学式: C₇H₅FN₂O₅
• 分子量: 216.126
• InChiKey: RBUNZLFXLZNTFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(5'-fluoro-3'H-2',4'-pyridinediketone)-3-oxo-benzyl propionate 在 palladium 10% on activated carbon 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 3-(5'-fluoro-3'H-2',4'-pyridinediketone)-3-oxo propionic acid
  参考文献：
  名称：

  Polysacchocride prodrug of 5-fluorouracil (5-FU) with enhanced target specificity for galectin-3 expressing cancers

  摘要：

  该应用程序披露了一种新型前药及其合成方法的实施方式。该前药包括一个含半乳糖的多糖，与5-氟尿嘧啶（5-FU）共价连接。作为半乳糖多糖骨架的一部分的半乳糖残基介导了前药与在各种癌症中表达的凝集素galectin-3之间的结合。这种含半乳糖的多糖是从各种植物材料中分离出来并与5-FU共价结合。可以使用各种配方（全身或局部形式）来向靶向表达galectin-3的癌症患者管理这种释放5-FU的前药。

  公开号：

  US20080004237A1

文献信息

• Novel polysaccharide pro-drug 5-fluorouracil (5-FU) with enhanced target specificity for colorectal cancer and its preparation methods
  申请人：Tam C. Joemy

  公开号：US20080085871A1

  公开（公告）日：2008-04-10

  This invention describes a novel polysaccharide prodrug of 5-fluorouracil (5-FU) with enhanced target specificity for colorectal cancer treatment, and its preparation methods. The prodrug is synthesized by chemically linking anti-cancer drug 5-fluorouracil (5-FU) with a specially selected polysaccharide with molecular weight of 10 5 ˜10 7 Da containing galactose residues. Its distinctive characteristics are that it is a prodrug synthesized by chemically linking polysaccharides with 5-FU through different bridge links for the targeted treatment of colorectal cancer; that the polysaccharides in the chemical compound contain galactose residues; and that these polysaccharides are prepared from natural gums or plant materials. Due to these unique characteristics, as an oral preparation, the polysaccharide component of this novel prodrug can protect the active agent 5-FU from absorption (or metabolism) in the upper gastrointestinal tract and deliver a high concentration of the 5-FU to the colorectal area. Upon reaching the colorectal area, the 5-FU-galactose portion of the prodrug will bind to galectin-3, a-galactoside-binding protein implicated in tumor progression by interactions with its ligands, such as TF (Thomsen-Friedenreich, Galb3GalNAc), Tn (GalNAcaThr/Ser), and Sialy-Tn with galactose residues, which are highly expressed among colorectal cancer cells. Finally, the active 5-FU component will be released locally from the polysaccharide via enzymatic hydrolysis from the local bacterial flora, allowing it to actively kill the colorectal cancer cells. In summary, this novel target-specific prodrug can enhance the selectivity of 5-FU and increase its therapeutic effects in the treatment of colorectal cancer. In addition, with this enhanced target specificity, it is possible to maximize the 5-FU efficacy in cancer patients by having either less toxicity with the same or higher therapeutic dose, and/or administer a lower dosage (if so desired) to achieve the same therapeutic effects, but with much less toxicity. Multiple examples of various approaches to synthesize this novel prodrug are enclosed herein along with several animal model experiments to substantiate the claims as stated above.

  这项发明描述了一种新型的多糖前药5-氟尿嘧啶（5-FU），具有增强的靶向特异性，用于结直肠癌治疗，以及其制备方法。该前药是通过化学连接抗癌药物5-氟尿嘧啶（5-FU）与分子量为105˜107Da、含有半乳糖残基的特选多糖进行合成的。其独特特点在于，它是通过不同的桥接链将多糖与5-FU化学连接而合成的前药，用于靶向治疗结直肠癌；化合物中的多糖含有半乳糖残基；这些多糖是从天然树胶或植物材料中制备的。由于这些独特特点，作为口服制剂，这种新型前药的多糖成分可以保护活性成分5-FU不被上消化道吸收（或代谢），并将高浓度的5-FU传递到结直肠区域。到达结直肠区域后，前药的5-FU-半乳糖部分将与半乳糖结合蛋白galectin-3结合，后者通过与其配体的相互作用，如TF（Thomsen-Friedenreich，Galb3GalNAc）、Tn（GalNAcaThr/Ser）和带有半乳糖残基的Sialy-Tn，参与了肿瘤进展，在结直肠癌细胞中高表达。最终，活性的5-FU成分将通过局部细菌群的酶水解从多糖中释放出来，从而能够主动杀死结直肠癌细胞。总之，这种新型靶向特异性前药可以增强5-FU的选择性，并增加其在结直肠癌治疗中的治疗效果。此外，通过增强的靶向特异性，可以通过减少毒性或使用相同或更高的治疗剂量来最大化癌症患者的5-FU疗效，或者以更低剂量（如果需要）来达到相同的治疗效果，但毒性更小。本文附有多种合成这种新型前药的方法示例，以及几个动物模型实验，以证实上述声明。