(2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoic acid | 136431-21-5

• 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: (2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoic acid
• CAS: 136431-21-5
• 化学式: C₉H₁₀FN₃O₅
• 分子量: 259.194
• InChiKey: TURKCZRJGNRDGN-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  4 ’-去甲去氧鬼臼毒素 、 (2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到[4-[(5R,5aR,8aR)-6-oxo-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]-2,6-dimethoxyphenyl] (2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7

  摘要：

  In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N-1-ly acetic)- amino acids (or 5-fluorouracil-N-1-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.005
• 作为产物：
  描述：

  2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸 在 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoic acid
  参考文献：
  名称：

  喜树碱和5-氟尿嘧啶新型共轭物作为细胞毒剂的合成及生物学评价

  摘要：

  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

  DOI：

  10.1590/s0103-50532011000200017

文献信息

• 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).
• 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
• Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7
  作者：Wen-Ting Huang、Jie Liu、Jian-Fei Liu、Ling Hui、Yi-Lan Ding、Shi-Wu Chen

  DOI：10.1016/j.ejmech.2011.12.005

  日期：2012.3

  In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N-1-ly acetic)- amino acids (or 5-fluorouracil-N-1-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.