4-(1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)-N-(pyrene-2-yl)butanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: 4-(1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)-N-(pyrene-2-yl)butanamide
• 英文别名: 4-[1-[(2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]triazol-4-yl]-N-pyren-2-ylbutanamide
• 化学式: C₃₂H₃₀N₆O₅
• 分子量: 578.627
• InChiKey: ZHQFTFDQBREYAM-ZRRKCSAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(pyren-2-yl)hexa-5-ynamide 、 齐多夫定 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-(1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)-N-(pyrene-2-yl)butanamide
  参考文献：
  名称：

  用于光动力抗肿瘤治疗的脱氧胸苷-喹啉共轭 衍生物及合成方法

  摘要：

  本发明公开了用于光动力抗肿瘤治疗的脱氧胸苷‑喹啉共轭衍生物，该衍生物以通式表示，其中n为1、3、5或7，R1和R2各自独立，表示氢原子或者卤素原子；本发明还公开了该新型衍生物的合成方法及其应用。该衍生物具有抗肿瘤作用，尤其是在紫外光照射下具有光动力效应，其抗肿瘤效果增强。

  公开号：

  CN104876992B

文献信息

• Structure–activity relationship study of anticancer thymidine–quinoxaline conjugates under the low radiance of long wavelength ultraviolet light for photodynamic therapy
  作者：Dejun Zhang、Huaming Liu、Qiong Wei、Qibing Zhou

  DOI：10.1016/j.ejmech.2015.11.006

  日期：2016.1

  Thymidine quinoxaline conjugate (dT-QX) is a thymidine analog with selective cytotoxicity against different cancer cells. In this study, the structure activity relationship study of dT-QX analogs was carried out under the low radiance of black fluorescent (UVA-1) light. Significantly enhanced cytotoxicity was observed under UVA-1 activation among analogs containing both thymidine and quinoxaline moieties with different length of the linker, stereochemical configuration and halogenated substituents. Among these analogs, the thymidine dichloroquinoxaline conjugate exhibited potent activity under UVA-1 activation as the best candidate with EC50 at 0.67 mu M and 1.3 mu M against liver and pancreatic cancer cells, respectively. In contrast, the replacement of thymidine moiety with a galactosyl residue or the replacement of quinoxaline moiety with a fluorescent pyrenyl residue or a simplified diketone structure resulted in the full loss of activity. Furthermore, it was revealed that the low radiance of UVA-1 at 3 mW/cm(2) for 20 mm was sufficient enough to induce the full cytotoxicity of thymidine dichloroquinoxaline conjugate and that the cytotoxic mechanism was achieved through a rapid and steady production of reactive oxygen species. (C) 2015 Elsevier Masson SAS. All rights reserved.