2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸 | 56059-30-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸
• 英文名称: 5-fluorouracil-1-acetic acid
• 英文别名: 5-fluorouracil-1-yl acetic acid；2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetic acid；1-carboxymethyl-5-fluorouracil；5-fluorouracil acetic acid；2-(5-fluorouracil) acetic acid；2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetic acid
• CAS: 56059-30-4
• 化学式: C₆H₅FN₂O₄
• 分子量: 188.115
• InChiKey: CPMUSDZOVZYEJJ-UHFFFAOYSA-N

物化性质

• 熔点：
  253-256 °C
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温下应保持干燥和密封保存。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-Fluoro-3,4-dihydro-2,4-dioxo-1(2h)-pyrimidineacetic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 5-Fluoro-3,4-dihydro-2,4-dioxo-1(2h)-pyrimidineacetic acid
CAS number: 56059-30-4

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C6H5FN2O4
Molecular weight: 188.1

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen fluoride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸 在 水 、 sodium hydroxide 作用下， 生成 5-氟脲嘧啶
  参考文献：
  名称：

  携带5-氟尿嘧啶的卟啉的合成及体外释药

  摘要：

  紫菜聚糖是红藻紫菜的硫酸化多糖，具有优良的生物活性，尤其是免疫活性。为了提供一种具有5-FU缓释、降低副作用的水溶性5-FU大分子前药，我们采用卟啉作为药物载体，将5-FU固定在卟啉的6位上。乙酰基间隔基通过酯键。在 37 摄氏度的三种不同介质中体外研究了 5-FU 从获得的缀合物中的化学特性和释放行为。结果表明，所有结合物的释放机制都是典型的Fickian扩散。然而，需要对动物模型进行进一步的体内研究来确定该系统的效率。(C) 2009 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.carbpol.2009.09.009
• 作为产物：
  描述：

  5-氟脲嘧啶 在 potassium hydroxide 、 溴乙酸 作用下， 以 水 为溶剂， 反应 0.5h， 生成 2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸
  参考文献：
  名称：

  [2-(5′-氟尿嘧啶)乙酸-二乙基二硫代氨基甲 酸]酐及在制备抗癌药物中的应用

  摘要：

  本发明属于抗肿瘤药物制备技术领域，具体涉及一种5‑氟尿嘧啶与二硫代氨基甲酸盐化合物P1的设计、合成及其制备抗肿瘤药物中的应用，尤其涉及一种[2‑（5´‑氟尿嘧啶）乙酸‑二乙基二硫代氨基甲酸]酐及其在制备抗肿瘤药物中的应用。将5‑氟尿嘧啶进行一定的衍生之后，与二乙基二硫代氨基甲酸钠通过化学键结合，设计并合成了一个潜在的多靶点抗肿瘤新药。细胞毒性实验验证了其抗肿瘤活性，并且联合铜离子使用，其对应的肿瘤细胞生长的抑制能力显著增强。肿瘤细胞克隆形成实验进一步表明其抑制细胞增殖活性的能力，细胞转移实验也显示出其对肿瘤细胞转移能力的抑制作用。

  公开号：

  CN111592498B

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 antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins
  作者：Di-Zao Li、Qiang-Zhe Zhang、Cun-Ying Wang、Yan-Ling Zhang、Xing-Yu Li、Ji-Tao Huang、Hong-Yan Liu、Zhao-Di Fu、Hua-Xian Song、Jin-Ping Lin、Teng-Fei Ji、Xian-Dao Pan

  DOI：10.1016/j.ejmech.2016.11.013

  日期：2017.1

  selected to be evaluated for in vivo antitumor activity against H22, BGC-823 and Bel-7402 in mice. In vivo testing results indicated that 12 and 13 had antitumor activity against mouse liver carcinoma H22 close to Paclitaxel and cyclophosphamide. 12 had similar antitumor activity against human gastric carcinoma BGC-823 in nude mice compared to irinotecan (3) and possessed better antitumor activity against

  一系列新颖的取代的尿嘧啶-1'（Ñ） -乙酸的酯（6 - 20）的喜树碱（彩色显像管）的酰化方法合成。评估了这些新化合物对肿瘤细胞系A549，Bel7402，BGC-823，HCT-8和A2780的体外抗肿瘤活性。体外结果显示，与CPT（1）和拓扑替康（TPT，2）相比，大多数衍生物表现出可比或更高的细胞毒性，其中12和13具有最佳疗效。四种化合物，9，12，13和16选择用于评估小鼠中针对H 22，BGC-823和Bel-7402的体内抗肿瘤活性。体内测试结果表明，12和13具有对小鼠肝癌H 22的抗肿瘤活性，接近紫杉醇和环磷酰胺。12相比伊立替康（具有针对人胃癌BGC-823相似的抗肿瘤活性在裸鼠3）并拥有在裸鼠中对人肝癌的Bel-7402更好的抗肿瘤活性比2。还发现12显示出类似的机制，但与2相比，对拓扑异构酶I（Topo I）的抑制活性更好。这些发现表明，CPTs的20（S）-O-
• Design and synthesis of parthenolide and 5-fluorouracil conjugates as potential anticancer agents against drug resistant hepatocellular carcinoma
  作者：Yahui Ding、Shengzu Li、Weizhi Ge、Zhongquan Liu、Xuhai Zhang、Mengmeng Wang、Tianyang Chen、Yue Chen、Quan Zhang

  DOI：10.1016/j.ejmech.2019.111706

  日期：2019.12

  15d could reverse drug resistance by inhibiting MDR1, ABCC1 and ABCG2 to increase the intracellular drug accumulation and induce apoptosis of Bel-7402/5-FU cells through mitochondria mediated pathway. On the base of these results, compound 15d is deserved to be further investigated as a potential anti-HCC lead compound for ultimate discovery of pathenolide-based anti-cancer drug.

  合成并评估了一系列二十三种单烯酚内酯-5-氟尿嘧啶（5-FU）缀合物，并评估了其对人肝癌细胞系Bel-7402和对5-氟尿嘧啶耐药的人肝癌细胞系Bel-7402 /的抗癌活性5-氟尿嘧啶 初步的构效关系进行了讨论。最具活性的化合物15d对Bel-7402 / 5-FU细胞系表现出高活性，IC50值为2.25μM，与母体化合物小白菊内酯（IC50 = 12.98μM）相比，显示出5.8倍的改善。15d初步分子机制的研究表明，15d可以通过抑制MDR1，ABCC1和ABCG2逆转耐药性，从而增加细胞内药物的积累并通过线粒体介导的途径诱导Bel-7402 / 5-FU细胞凋亡。
• Synthesis and biological evaluation of novel conjugates of camptothecin and 5-flurouracil as cytotoxic agents
  作者：Liu Yang、Chun-Yan Zhao、Ying-Qian Liu

  DOI：10.1590/s0103-50532011000200017

  日期：——

  that the biological life span of their lactone forms in human and mouse plasma significantly increased compared with their mother compound 1. Quantitative structure-activity relationship (QSAR) method was then applied for developing linear models to predict the cytotoxic activities of these derivatives that have not yet been synthesized or experimentally tested. In addition, molecular docking was used

  首先合成了一系列喜树碱和5-氟尿嘧啶的新型结合物，研究了它们对两种人肿瘤细胞系（SGC-7901和A-549）的细胞毒活性以及体外药代动力学测定内酯的稳定性。在这些化合物中，大多数测试的结合物显示出与2相当或更好的细胞毒活性，但与1相比，效力更弱。特别是，结合物10b和10d对A-549具有高活性，IC50值分别为0.45和0.38 µmol L-1。同样，对代表化合物10b的内酯水平进行的体外药代动力学测定表明，与它们的母体化合物1相比，其内酯形式在人和小鼠血浆中的生物寿命显着增加。然后将定量构效关系（QSAR）方法用于开发线性模型，以预测这些尚未合成或未经实验测试的衍生物的细胞毒活性。此外，分子对接用于阐明这些衍生物与人DNA拓扑异构酶I的结合方式。在这些衍生物及其受体之间观察到重要的氢键相互作用。分子建模和QSAR研究的结果可指导具有更高抗肿瘤活性的新型缀合物的设计。在这些衍生物及其
• Preliminary SAR and biological evaluation of potent HIV-1 protease inhibitors with pyrimidine bases as novel P2 ligands to enhance activity against DRV-resistant HIV-1 variants
  作者：Mei Zhu、Ling Ma、Huiyu Zhou、Biao Dong、Yujia Wang、Zhen Wang、Jinming Zhou、Guoning Zhang、Juxian Wang、Chen Liang、Shan Cen、Yucheng Wang

  DOI：10.1016/j.ejmech.2019.111866

  日期：2020.1

  to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2' ligand, displayed

  将嘧啶碱基（核酸的基本成分）引入P2配体可能会增强人类免疫缺陷病毒1（HIV-1）蛋白酶抑制剂的效力，因为羰基和氨基会促进广泛的氢键相互作用的形成。在这项工作中，我们提供的证据是抑制剂10e，以N-2-（2,4-二氧代-3,4-二氢嘧啶-1（2H）-基）乙酰胺为P2配体，以4-甲氧基苯基磺酰胺为P2'配体具有显着的酶抑制和抗病毒活性，体外IC50为2.53 nM，体内对野生型HIV-1的抑制率为68％，细胞毒性低。该抑制剂还对DRV耐药的HIV-1变体表现出明显的抗病毒活性，这对进一步研究具有重要的价值。