[(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] 2-[[(2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoyl]amino]acetate | 1301175-67-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: [(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] 2-[[(2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoyl]amino]acetate
• CAS: 1301175-67-6
• 化学式: C₃₁H₂₇FN₆O₉
• 分子量: 646.589
• InChiKey: AAXWUHHYRASNLU-IWAYBZMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  47
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  193
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  喜树碱 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 [(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] 2-[[(2S)-2-[[2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetyl]amino]propanoyl]amino]acetate
  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).