5-氟尿嘧啶-1-琥珀酸苄基酯 | 201210-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-氟尿嘧啶-1-琥珀酸苄基酯
• 英文名称: succinic acid benzyl ester (5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl ester
• 英文别名: benzyl ((5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)succinate；5-fluorouracil-1-succinic benzyl ester；1-O-benzyl 4-O-[(5-fluoro-2,4-dioxopyrimidin-1-yl)methyl] butanedioate
• CAS: 201210-70-0
• 化学式: C₁₆H₁₅FN₂O₆
• 分子量: 350.303
• InChiKey: XMPUIJJJPBJGMG-UHFFFAOYSA-N

物化性质

• 熔点：
  124-126 °C
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-氟尿嘧啶-1-琥珀酸苄基酯 在 palladium on activated charcoal 1,4-环己二烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-O-[(5-fluoro-2,4-dioxopyrimidin-1-yl)methyl] 4-O-(2,3,4,5,6-pentafluorophenyl) butanedioate
  参考文献：
  名称：

  Synthesis and Reactivity of 5-Fluorouracil/Cytarabine Mutual Prodrugs

  摘要：

  Two mutual prodrugs, in which two different anti-cancer drugs are attached to the same molecule via labile linkages, are synthesized and examined kinetically. One of the mutual prodrugs loses a drug component under physiological conditions within an hour, but the other mutual prodrug (having a longer spacer between the two drugs) is stable to chemical degradation even at higher pH values. Thus, enzymatic hydrolysis alone will release the two anti-cancer drugs. The potential value of anti-cancer mutual prodrugs is discussed.

  DOI：

  10.1021/jo971076p
• 作为产物：
  描述：

  琥珀酸苄酯 在 磺酰氯 、 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-氟尿嘧啶-1-琥珀酸苄基酯
  参考文献：
  名称：

  Synthesis and cytotoxicity of 5-fluorouracil/diazeniumdiolate conjugates

  摘要：

  5-Fluorouracil/diazeniumdiolate conjugates were first synthesized, and showed greater cytotoxicities than 5-fluorouracil for DU 145 human prostate and HeLa cancer cells. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.003

文献信息

• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• Synthesis and Characterization of New Liver Targeting 5-Fluorouracil-Cholic Acid Conjugates
  作者：Shan Qian、Jian-Bo Wu、Xiao-Chun Wu、Jie Li、Yong Wu

  DOI：10.1002/ardp.200900075

  日期：2009.9

  of this work was to develop a liver‐specific antihepato carcinoma agent. A series of 5‐fluorouracil / cholic acid conjugates (5‐FU‐cholic acid conjugates) were prepared and tested for their chemical characteristics and bio‐distribution properties. The in‐vitro stability trial showed 5‐FU‐cholic acid conjugates could be completely hydrolyzed by heating at 70°C in an acidic solution, pH = 1, for 5 min

  这项工作的目的是开发一种肝脏特异性抗肝癌药物。制备了一系列 5-氟尿嘧啶/胆酸结合物（5-FU-胆酸结合物）并测试了它们的化学特性和生物分布特性。体外稳定性试验表明，5-FU-胆酸结合物可以通过在 70°C、pH = 1 的酸性溶液中加热 5 分钟来完全水解。这些化合物的快速完全水解可以与快速分离和分析方法兼容，以缩短分析时间。通过测量器官组织中再生 5-FU 的浓度来评估口服给药后几个时间点 5-FU-胆酸结合物在小鼠不同器官中的分解速度。将结果与对照组的结果进行比较，这是一组口服 5-FU 的小鼠。口服前药后，小鼠肝组织中 5-FU 的浓度显着升高，远高于仅口服 5-FU 时的浓度。结果表明，以胆酸为药物载体，提高肝脏靶向治疗疗效的可行性。
• Self-assembly of a 5-fluorouracil-dipeptide hydrogel
  作者：Yuan Sun、Jonah A. Kaplan、Aileen Shieh、Hui-Lung Sun、Carlo M. Croce、Mark W. Grinstaff、Jon R. Parquette

  DOI：10.1039/c6cc01195k

  日期：——

  The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported.

  5-氟尿嘧啶双赖氨酸共轭物自组装成自支撑水凝胶，由纠缠的纳米纤维或直径分别为10和16纳米的刚性纳米管组成。
• Selective bone targeting 5-fluorouracil prodrugs: Synthesis and preliminary biological evaluation
  作者：Liang Ouyang、Dongsheng He、Jing Zhang、Gu He、Bo Jiang、Qiang Wang、Zhengjun Chen、Junzhu Pan、Yanhua Li、Li Guo

  DOI：10.1016/j.bmc.2011.05.004

  日期：2011.6

  Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP. The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs. (C) 2011 Elsevier Ltd. All rights reserved.
• Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents
  作者：Ewa Mironiuk-Puchalska、Olena Karatsai、Agnieszka Żuchowska、Wojciech Wróblewski、Filip Borys、Lilya Lehka、Maria Jolanta Rędowicz、Mariola Koszytkowska-Stawińska

  DOI：10.1016/j.bioorg.2023.106784

  日期：2023.11