2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid | 104724-48-3

• 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
• 英文名称: 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid
• 英文别名: 2(R)-(5-fluorouracil-1-yl)acetylglycin；2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]acetic acid
• CAS: 104724-48-3
• 化学式: C₈H₈FN₃O₅
• 分子量: 245.167
• InChiKey: XRXXZWHTTHOTRC-UHFFFAOYSA-N

物化性质

• 熔点：
  257-259 °C(Solv: ethanol (64-17-5))
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid 、 L-天冬氨酸二甲酯盐酸盐 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以48%的产率得到(S)-dimethyl 2-(2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetamido)succinate
  参考文献：
  名称：

  The Synthesis and Anticancer Activities of Peptide 5-fluorouracil Derivatives

  摘要：

  为了测试体外抗癌活性，我们设计并合成了一系列新的多肽 5-氟尿嘧啶衍生物。结果表明，多肽 5-氟尿嘧啶衍生物对人类 HL-60 和 Bel-7402 细胞株具有抗癌活性。化合物的结构是通过 1H NMR、13C NMR、IR、质谱和元素分析确定的。

  DOI：

  10.3184/030823409x431364
• 作为产物：
  描述：

  methyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetate 在 sodium hydroxide 、 水 作用下， 以86%的产率得到2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid
  参考文献：
  名称：

  The Synthesis and Anticancer Activities of Peptide 5-fluorouracil Derivatives

  摘要：

  为了测试体外抗癌活性，我们设计并合成了一系列新的多肽 5-氟尿嘧啶衍生物。结果表明，多肽 5-氟尿嘧啶衍生物对人类 HL-60 和 Bel-7402 细胞株具有抗癌活性。化合物的结构是通过 1H NMR、13C NMR、IR、质谱和元素分析确定的。

  DOI：

  10.3184/030823409x431364

文献信息

• 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
• Design and synthesis of novel camptothecin/5-fluorouracil conjugates as cytotoxic agents
  作者：Ying-Qian Liu、Wei Dai、Liu Yang、Hong-Yu Li

  DOI：10.1080/14786411003792181

  日期：2011.11

  In an effort to overcome several limitations associated with the synthesis of camptothecin (CPT), seven conjugates (10a-10g) composed of CPT and a 5-fluorouracil derivative joined by suitable dipeptide linkages were synthesised, and their cytotoxic activity against four human tumour cell lines as well as an in vitro pharmacokinetic determination of their lactone stability were studied. Among these compounds, most tested conjugates showed cytotoxic activities comparable or superior to CPT-11 (2), but they were less potent when compared with CPT (1). Interestingly, all of the compounds showed selective inhibitory activities against BGC-823, with IC50 values lower than 0.1 mu mol, which is more potent than CPT-11 (2). Also, the in vitro pharmacokinetic determination of the lactone levels of the representative compound 10b showed that the biological life span of their lactone forms in human and mouse plasma were significantly increased when compared with their mother compound CPT (1).
• CHEN, QUSHENG;HU, WEIDONG, J. WUHAN UNIV. (NATUR. SCI. ED.),(1987) N 3, 89-94
  作者：CHEN, QUSHENG、HU, WEIDONG

  DOI：——

  日期：——
• The Synthesis and Anticancer Activities of Peptide 5-fluorouracil Derivatives
  作者：Xiaowei Yan、Maolin Hu、Qian Miao、Shun Wang、Kejian Zhao

  DOI：10.3184/030823409x431364

  日期：2009.4

  A new series of peptide 5-fluorouracil derivatives was designed and synthesised in order to test in vitro anticancer activities. The results indicated that peptide 5-fluorouracil derivatives possessed anticancer activities against human HL-60 and Bel-7402 cell lines. The structures of the compounds were determined by means of ¹H NMR, ¹³C NMR, IR, mass spectra and elemental analyses.

  为了测试体外抗癌活性，我们设计并合成了一系列新的多肽 5-氟尿嘧啶衍生物。结果表明，多肽 5-氟尿嘧啶衍生物对人类 HL-60 和 Bel-7402 细胞株具有抗癌活性。化合物的结构是通过 1H NMR、13C NMR、IR、质谱和元素分析确定的。