1-(ethoxycarbonyl)-5-fluorouracil | 21839-33-8

• 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: 1-(ethoxycarbonyl)-5-fluorouracil
• 英文别名: 1-ethyloxycarbonyl-5-fluorouracil；1-ethoxycarbonyl-5-fluorouracil；Ethyl 5-fluoro-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxylate；ethyl 5-fluoro-2,4-dioxopyrimidine-1-carboxylate
• CAS: 21839-33-8
• 化学式: C₇H₇FN₂O₄
• 分子量: 202.142
• InChiKey: XRHUFADXPHBXFZ-UHFFFAOYSA-N

物化性质

• 熔点：
  128-130 °C(Solv: benzene (71-43-2))
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  1-(ethoxycarbonyl)-5-fluorouracil 生成 5-氟脲嘧啶
  参考文献：
  名称：

  BUUR A.; BUNDGAARD H., J. PHARM. SCI., 75,(1986) N 5, 522-527

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氟脲嘧啶 、 氯甲酸乙酯 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以31.5%的产率得到1-(ethoxycarbonyl)-5-fluorouracil
  参考文献：
  名称：

  Studies on antitumor agents. V. Syntheses and antitumor activities of 5-fluorouracil derivatives.

  摘要：

  合成了六类氟尿嘧啶（5-FU）衍生物，即2,4-二-O-取代、2-O-取代、4-O-取代、1,3-二取代、1-取代和3-取代的化合物。在大鼠口服这些化合物后，测定了5-FU的血药浓度。在O-取代衍生物中，4-O-取代衍生物最容易被激活为5-FU，其次是2-O-取代衍生物。在N-取代衍生物中，酰基和磺酰基衍生物显示出最高的5-FU释放能力，1-烷氧甲基取代衍生物的释放能力较低。N-烷基取代衍生物未被激活为5-FU。选择了几种在血中5-FU水平高于1-(四氢-2-呋喃基)-5-氟尿嘧啶（Thf-FU）的化合物，以及一些相关化合物，并对其抗肿瘤活性进行了检测。2-O-取代衍生物，2-丁氧基-5-氟-4(1H)-嘧啶酮（11）和2-苄氧基-5-氟-4(1H)-嘧啶酮（19），与Thf-FU一样有效。2,4-二-O-取代衍生物，2,4-二丁氧基-5-氟嘧啶（1）和2,4-二苄氧基-5-氟嘧啶（6），对艾氏癌和肉瘤180的活性与Thf-FU相同。1-取代衍生物，1-乙氧甲基-5-氟尿嘧啶（49）和1-(1-乙氧基-1-苯甲基)-5-氟尿嘧啶（50），发现与Thf-FU一样有效。

  DOI：

  10.1248/cpb.30.4258

文献信息

• Studies of antitumor-active 5-fluorouracil derivatives. I. Synthesis of N-phthalidyl 5-fluorouracil derivatives.
  作者：SUSUMU KAMATA、NOBUHIRO HAGA、TAKEAKI MATSUI、WATARU NAGATA

  DOI：10.1248/cpb.33.3160

  日期：——

  Several 5-fluorouracil derivatives in which the phthalidyl (1, 3-dihydro-3-oxoisobenzofuran-1-yl) group, appropriately substituted on its benzene ring, is substituted at the N (1)-or N (3)-position or at both positions were synthesized, and their antitumor activities were evaluated. Among these compounds, 1-(1, 3-dihydro-3-oxoisobenzofuran-1-yl)-5-fluorouracil (3a, 590-S) was shown to be markedly active against several experimental tumor systems. Several methods for a simple and efficient large-scale preparation of 3a were examined. The large-scale preparation of 3a was effected most efficiently by the condensation of 5-fluorouracil with the quaternary ammonium salt of 3-bromophthalide in the presence of a base. The synthesis of (+)- and (-)-3a is also described.

  合成了几种5-氟尿嘧啶衍生物，其中苯并二氢呋喃酮（1,3-二氢-3-氧异苯并呋喃-1-基）基团在其苯环上适当取代，并在N(1)或N(3)位或两个位置上进行取代，并评估了它们的抗肿瘤活性。在这些化合物中，1-(1,3-二氢-3-氧异苯并呋喃-1-基)-5-氟尿嘧啶（3a，590-S）显示出对几种实验性肿瘤系统有显著的活性。研究了几种简单高效的3a大规模制备方法。通过5-氟尿嘧啶与3-溴邻苯二甲酰亚胺的季铵盐在碱存在下缩合，最有效地实现了3a的大规模制备。还描述了(+)-和(-)-3a的合成。
• Studies on the syntheses of heterocyclic compounds. 845. Studies on the synthesis of chemotherapeutics. 10. Synthesis and antitumor activity of N-acyl- and N-(alkoxycarbonyl)-5-fluorouracil derivatives
  作者：Tetsuji Kametani、Kazuo Kigasawa、Mineharu Hiiragi、Kikuo Wakisaka、Seiji Haga、Yasuo Nagamatsu、Hideo Sugi、Kazunaga Fukawa、Osamu Irino

  DOI：10.1021/jm00186a008

  日期：1980.12

  A number of N-acyl and N-(alkoxycarbonyl)-5-fluorouracil derivatives possessing, for example, benzoyl, o-toluyl, acetyl, propionyl, heptanoyl, ethoxycarbonyl, phenoxycarbonyl, and benzyloxycarbonyl groups as N1 and/or N3 substituents were synthesized, and their antitumor activities were evaluated. The synthesis was achieved by a direct and two-step acylation of 5-fluorouracil and by selective N1-deacetylation

  合成了许多具有例如N 1和/或N 3取代基的苯甲酰基，邻甲苯甲酰基，乙酰基，丙酰基，庚酰基，乙氧基羰基，苯氧基羰基和苄氧基羰基的N-酰基和N-（烷氧基羰基）-5-氟尿嘧啶衍生物。 ，并评估了它们的抗肿瘤活性。通过在适当的反应条件下对5-氟尿嘧啶进行直接和两步酰化，以及对N1-乙酰基-N3-取代的5-氟尿嘧啶进行选择性的N1-脱乙酰化，可以实现合成。几种N3-苯甲酰基-和N3-邻甲苯基-5-氟尿嘧啶衍生物具有显着的抗实验肿瘤活性，并且发现其中N1-乙酰基-N3-邻甲苯基-5-氟尿嘧啶是最有前途的。进一步的调查显示，与1或FT-207相比，12可以保留对各种肿瘤更高的活性，并且毒性更低，血液水平更高。
• Prodrugs of 5-Fluorouracil V. 1-Alkoxycarbonyl Derivatives as Potential Prodrug Forms for Improved Rectal or Oral Delivery of 5-Fluorouracil
  作者：Anders Buur、Hans Bundgaard

  DOI：10.1002/jps.2600750520

  日期：1986.5

  The hydrolysis and physicochemical properties of seven 1-alkoxycarbonyl derivatives of 5-fluorouracil were studied to assess their potential as prodrugs with the aim of enhancing the delivery characteristics of the parent drug. All derivatives were hydrolyzed to quantitatively yield 5-fluorouracil. The pH-rate profiles for the hydrolysis were measured. The rates of hydrolysis were markedly accelerated

  研究了七种5-氟尿嘧啶的1-烷氧基羰基衍生物的水解和理化性质，以评估其作为前药的潜力，目的是增强母体药物的递送特性。水解所有衍生物以定量产生5-氟尿嘧啶。测量了水解的pH速率曲线。在血浆存在下，水解速度显着加快，在80％的人体血浆中，水解的半衰期少于4分钟。所述衍生物比5-氟尿嘧啶更具亲脂性，但是其水溶性仅稍微降低，或者对于一种衍生物，其水溶性甚至大于5-氟尿嘧啶。兔子的初步吸收研究表明，直肠给药1-（丁氧羰基）-5-氟尿嘧啶后5-氟尿嘧啶的绝对生物利用度为100％，而5-氟尿嘧啶自身给药后无吸收。建议前药衍生物可用于增强母体药物的口服和/或直肠递送。
• Enhancer of anti-tumour effect
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0068268A1

  公开（公告）日：1983-01-05

  N6-acylated 3'-deoxyadenosines or phosphates thereof are disclosed as being effective for enhancing anti-tumor effect afforded by irradiation of or administration of an anti-tumor pharmaceutical to tumor-bearing animals.

  已公开的 N6-酰化 3'-脱氧腺苷或其磷酸酯可有效增强肿瘤动物通过照射或服用抗肿瘤药物所获得的抗肿瘤效果。
• Synthesis of 3‐alkylcarbonyloxymethyl derivatives of 5‐fluorouracil
  作者：William J. Roberts、Kenneth B. Sloan

  DOI：10.1002/jhet.5570390509

  日期：2002.9

  Abstract3‐Alkylcarbonyloxymethyl derivatives of 5‐fluorouracil have been synthesized starting with 1‐ethyloxy‐carbonyl‐5‐fluorouracil. Alkylation of the starting material with alkylcarbonyloxymethyl iodides, generated from the corresponding chlorides by the Finkelstein reaction, in the presence of 1,8‐bis(dimethyl‐amino)naphthalene followed by deprotection with 1,1‐dimethylethylamine gave good yields (50‐60%) of the target derivatives after column chromatography. A 90% yield of 3‐acetyloxymethyl‐5‐fluorouracil was obtained when the corresponding commercially available bromide was used, instead of the in situ generated iodide, and the product could be isolated from the crude reaction by crystallization. An alternate path of sequential alkylation of 5‐fluorouracil with alkylcarbonyloxymethyl chlorides in the presence of tertiary amines, exhibiting different reactivities towards the chlorides, gave an excellent yield of 1‐acetyloxymethyl‐3‐propionyloxymethyl‐5‐fluorouracil in the one instance it was attempted, but subsequent deprotection of the 1‐position with methylamine gave only a 24% yield of 3‐propionyloxymethyl‐5‐fluorouracil.