5-氟-2,4-二氧代-3,4-二氢-1(2H)-嘧啶羰基氯化物 | 65202-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-氟-2,4-二氧代-3,4-二氢-1(2H)-嘧啶羰基氯化物
• 英文名称: 5-fluoro-2,4-dioxo-pyrimidine-1-carbonyl chloride
• 英文别名: 5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-carbonyl chloride；chloroformyl 5-FU；5-Fluoro-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carbonyl chloride；5-fluoro-2,4-dioxopyrimidine-1-carbonyl chloride
• CAS: 65202-29-1
• 化学式: C₅H₂ClFN₂O₃
• 分子量: 192.534
• InChiKey: UCCCNAVMLDLYQC-UHFFFAOYSA-N

物化性质

• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氟-2,4-二氧代-3,4-二氢-1(2H)-嘧啶羰基氯化物 在 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 5-fluoro-N-[7-(hydroxyamino)-7-oxoheptyl]-2,4-dioxopyrimidine-1-carboxamide
  参考文献：
  名称：

  [EN] HYDROXAMIC ACID DERIVATIVES
  [FR] DÉRIVÉS D'ACIDE HYDROXAMIQUE

  摘要：

  公开号：

  WO2010085377A3
• 作为产物：
  描述：

  5-fluorouracil-1-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-氟-2,4-二氧代-3,4-二氢-1(2H)-嘧啶羰基氯化物
  参考文献：
  名称：

  二氧化硅纳米载体顺序递送协同药物以增强肿瘤治疗。

  摘要：

  在本文中，杂化二氧化硅纳米颗粒已经被工程化以指导多种化学治疗药物响应于外部刺激例如pH的变化而顺序递送。纳米载体由常规的MCM-41型纳米颗粒组成，这些纳米颗粒已通过嫁接到外表面的有机配体（或茎）进行了功能化。茎被设计为“识别”互补分子，该分子充当“帽”以阻挡纳米颗粒的孔。首先，喜树碱通过扩散引入到孔中，然后通过分子识别覆盖孔。该帽是5-氟尿嘧啶的衍生物，用作协同化学疗法的第二种细胞毒性药物。体外测试显示，在pH 7.4时，药物的释放微不足道，因此避免了血液中的毒副作用。相反，茎/帽复合物在癌细胞的溶酶体区室（pH 5.5）中不稳定，在此处证实了药物的释放。此外，这种对环境敏感的系统表现出两种药物的协同作用，其中pH触发的细胞毒性帽释放释放，然后药物货物在孔内扩散受控释放，导致乳腺癌细胞基本完全消除。

  DOI：

  10.1039/c9tb02225b

文献信息

• 5-Fluorouracil Derivatives. XXII. Synthesis and Antitumor Activities of 1-Carbamoyl-5-fluorouracils.
  作者：Shoichiro OZAKI、Xiangzheng KONG、Yutaka WATANABE、Tomonori HOSHIKO、Toshikazu KOGA、Tomio OGASAWARA、Tsuneharu TAKIZAWA、Hiroshi FUJISAWA、Masaaki IIGO、Akio HOSHI

  DOI：10.1248/cpb.45.1372

  日期：——

  Fifty-four 1-carbamoyl-5-fluorouracils were synthesized from 5-fluorouracil and isocyanate or amine. Antitumor activity was tested in the L-1210 tumor system, and 11 compounds gave better values of therapeutic ratio than HCFU (1-hyxylcarbamoyl-5-fluorouracil). 1-(4-Methoxycyclohexylcarbamoyl)-5-fluorouracil gave the best result.

  从5-氟尿嘧啶和异氰酸酯或胺合成了54个1-羧酰胺基-5-氟尿嘧啶。在L-1210瘤株体系中测试了其抗肿瘤活性,有11个化合物的治疗比值优于HCFU(1-羟基羰酰胺基-5-氟尿嘧啶)。其中1-(4-甲氧基环己基羰酰胺基)-5-氟尿嘧啶的效果最佳。
• 5-Fluorouracil derivatives. IX. Synthesis and antitumor activities of (alkylthio)carbonyl-5-fluorouracils.
  作者：TOMONORI HOSHIKO、SHOICHIRO OZAKI、YUTAKA WATANABE、TOMIO OGASAWARA、SHIN YAMAUCHI、KEIJI FUJIWARA、AKIO HOSHI、MASAAKI IIGO

  DOI：10.1248/cpb.33.2832

  日期：——

  A series of 5-fluorouracil derivatives having (alkylthio) carbonyl groups at the 1-, 3-, and 1, 3-positions was synthesized and tested for antitumor activity against L-1210 leukemia in mice. Among them, 1-(octylthio) carbonyl-5-fluorouracil showed promising activity ; it gave a greater increase in life span than 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur), which are both in clinical use.

  合成了一系列在1、3位和1,3位具有（烷基硫）羰基的5-氟尿嘧啶衍生物，并测试了其对小鼠L-1210白血病的抗肿瘤活性。其中，1-（辛基硫）羰基-5-氟尿嘧啶表现出良好活性；其延长的生存期超过了临床使用的1-己基氨基-5-氟尿嘧啶（HCFU）和1-（2-四氢呋喃基）-5-氟尿嘧啶（Tegafur）。
• Polysacchocride prodrug of 5-fluorouracil (5-FU) with enhanced target specificity for galectin-3 expressing cancers
  申请人：Tam C. Joemy

  公开号：US20080004237A1

  公开（公告）日：2008-01-03

  This application discloses embodiments of a novel prodrug and its method of synthesis. The prodrug comprises a galactose-containing polysaccharide covalently linked to 5-fluorouracil (5-FU). The galactose residues that are part of the backbone of the galactose-containing polysaccharide mediate the binding between the prodrug and the lectin galectin-3 which is expressed in various cancers. The galactose-containing polysaccharide is isolated from various plant material and covalently bonded to 5-FU. Various formulations (parenteral, or other local or systemic forms) can be used to administer this 5-FU-releasing prodrug to target galectin-3 expressing cancers.

  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。
• 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。
• [EN] POLYETHYLENE GLYCOL-DRUG CONJUGATE AND USE THEREOF<br/>[FR] CONJUGUÉ POLYÉTHYLÈNE GLYCOL-MÉDICAMENT ET UTILISATION ASSOCIÉE<br/>[ZH] 聚乙二醇偶联药物及其用途
  申请人：CHONGQING UPGRA BIOTECHNOLOGY CO LTD

  公开号：WO2022242488A1

  公开（公告）日：2022-11-24

  一种聚乙二醇偶联药物及其用途，具体涉及式A所示的聚乙二醇偶联药物、其立体异构体或其药学上可接受的盐，用于制备所述聚乙二醇偶联药物、其立体异构体或其药学上可接受的盐的中间体，包含所述聚乙二醇偶联药物、其立体异构体或其药学上可接受的盐的药物组合物，以及所述聚乙二醇偶联药物、其立体异构体或其药学上可接受的盐在制备药物中的用途。