5'-succinyl-2',3'-isopropylidene-5-fluorouridine | 189275-14-7

• 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: 5'-succinyl-2',3'-isopropylidene-5-fluorouridine
• CAS: 189275-14-7
• 化学式: C₁₆H₁₉FN₂O₉
• 分子量: 402.333
• InChiKey: SANWZAZYOIQCNN-LHNIVKCTSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  146.15
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5'-succinyl-2',3'-isopropylidene-5-fluorouridine 在 三氟乙酸 作用下， 反应 1.0h， 以60%的产率得到5'-succinyl-5-fluorouridine
  参考文献：
  名称：

  Brusa; Dosio; Coppo, Il Farmaco, 1997, vol. 52, # 2, p. 71 - 81

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氟尿嘧啶核苷 在 硫酸 、 三乙胺 作用下， 反应 25.0h， 生成 5'-succinyl-2',3'-isopropylidene-5-fluorouridine
  参考文献：
  名称：

  [EN] CANCER THERAPY WITH MICROBUBBLES.
  [FR] TRAITEMENT DU CANCER AVEC DES MICROBULLES

  摘要：

  该发明涉及一种微气泡-化疗药物复合物，包括携带化疗药物组合的微气泡，用于治疗患者的癌症方法，其中所述化疗药物组合包括：(a) 5-氟嘧啶或其衍生物；(b) 伊立替康或其衍生物；和(c) 基于铂的化疗药物或其衍生物；其中所述方法包括同时、分开或顺序给予叶酸或其衍生物。该发明特别适用于用于治疗深部肿瘤和相关转移性疾病，例如胰腺癌的治疗。该发明还涉及微气泡-化疗药物复合物本身，以及它们的制备方法和含有它们的制药组合物，可选地与叶酸或叶酸衍生物结合在一起。

  公开号：

  WO2021198675A1

文献信息

• A Blood-brain Barrier Permeable Derivative of 5-Fluorouracil: Preparation, Intracellular Localization, and Mouse Tissue Distribution
  作者：Jung-Kyun Im、Goutam Biswas、Wan-Il Kim、Kyong-Tai Kim、Sung-Kee Chung

  DOI：10.5012/bkcs.2011.32.3.873

  日期：2011.3.20

  developed sorbitol-based G8 transporter, and the conjugate (7) with FITC was found to have an affinity toward mitochondria and to readily cross BBB to gain an entry into mouse brain. Measured by IC50, the conjugate (9) without the fluorophore showed enhanced cytotoxic activity toward two types of multidrug-resistant cell lines. These results strongly suggest that the sorbitol-based G8 transporter can be

  5-氟尿嘧啶 (5-FU) 是一种抗癌剂，与最近开发的基于山梨糖醇的 G8 转运蛋白共价连接，发现与 FITC 的缀合物 (7) 对线粒体具有亲和力并容易穿过 BBB 进入进入老鼠大脑。通过 IC50 测量，不含荧光团的偶联物 (9) 对两种类型的多药耐药细胞系表现出增强的细胞毒活性。这些结果强烈表明基于山梨糖醇的 G8 转运蛋白可用作良好的 CNS 传递载体。
• Antitumoral Activity of Liposomes and Immunoliposomes Containing 5-Fluorouridine Prodrugs
  作者：Paola Crosasso、Paola Brusa、Franco Dosio、Silvia Arpicco、Donatella Pacchioni、Francis Schuberî、Luigi Cattel

  DOI：10.1021/js9604467

  日期：1997.7

  Liposomes and immunoliposomes containing cytotoxic agents may be highly efficacious in intracavity therapy of malignancies confined principally to the peritoneal cavity. To assess the feasibility of this locoregional treatment, we prepared two derivatives of 5-fluorouridine (5-FUR), a highly cytotoxic metabolite of 5-fluorouracile, and incorporated them into REV liposomes, prepared with the reverse phase evaporation method. Encapsulation efficiency, drug leakage, and stability were determined, and size analysis and differential scanning calorimetry were carried out to evaluate the drug delivery potential of liposomes containing 5'-palmitoyl-5-FUR, 5'-succinyl-5-FUR, or the parent drug 5-FUR, The most suitable drug for encapsulation, in terms of minimum leakage and encapsulation efficiency, was 5'-palmitoyl-5-FUR, which differential scanning calorimetry indicated as being firmly anchored to the lipid bilayer. Thus, 5'-palmitoyl-5-FUR was chosen to prepare a chemotherapeutic liposome-monoclonal antibody conjugate (immunoliposome). The covalent linkage between antibody and liposome was realized by coupling the thiolated monoclonal antibody AR-3 with REV liposomes, containing N[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine. The cytotoxic activity of drug-bearing liposomes and immunoliposomes was evaluated on the HT-29 human colon adenocarcinoma cell line; the immunoliposomes had higher cytotoxicity than liposomes or 5-FUR. To explore the potential of these drug formulations in anticancer therapy, we ip injected liposomes or immunoliposomes into athymic mice ip grafted with human HT-29 cell line, in this mouse model, the immunoliposome containing 5'-palmitoyl-5-FUR displayed the best antitumoral activity, since on day 27 postgraft only 5% of residual tumor mass was present, compared to control mice: there was a close relationship between exposure time of tumor tissue to the drug and antitumor potency.