3-(2-(2,4-dinitrophenylamino)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione | 1402703-02-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2-(2,4-dinitrophenylamino)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-flouro-3-[(2-(2,4-dinitrophenylamino)ethyl)]pyrimidine-2,4-(1H)-dione；3-[2-(2,4-dinitroanilino)ethyl]-5-fluoro-1H-pyrimidine-2,4-dione
• CAS: 1402703-02-9
• 化学式: C₁₂H₁₀FN₅O₆
• 分子量: 339.24
• InChiKey: MMTUEQZVNXNHAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二硝基苯胺 在 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 3-(2-(2,4-dinitrophenylamino)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Interaction of 5-Fluorouracil and its derivatives with bovine serum albumin

  摘要：

  Fluorouracil (5-FU) and its derivatives are the most commonly used drugs to treat many types of cancer. Two dual functional agents, FUPAE and FUPAP, derived from 5-Fluorouracil (5-FU) have shown radiosensitizing activity but unlike their components were not cytotoxic. This study was designed to examine the interaction of BSA with 5-Fluorouracil (5-FU) and two of its derivatives; FUPAE and FUPAP at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV-Vis spectroscopic methods as well as molecular modelling were used to determine the drugs binding mode, the binding constants and the effects of drug complexation on BSA stability and conformation. Structural analysis showed that 5-Fluorouracil, FUPAE and FUPAP bind BSA via polypeptide polar groups with overall binding constants of K5-FU-BSA = 3.02(+/- 0.09) x 10(3), KFUPAE-BSA = 1.08(+/- 0.04) x 10(4), KFUPAP-BSA = 1.21(+/- 0.06) x 10(4) M-1. BSA conformation was altered by a major reduction of alpha-helix from 69% (free BSA) to 34% with 5-FU, 40% with FUPAE, 38% with FUPAP. These results suggest that serum albumins might act as carrier proteins for FUPAE and FUPAP in delivering them to target tissues. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jphotobiol.2011.11.004

文献信息

• Synthesis,<i>In Vitro</i>Cytotoxicity and Radiosensitizing Activity of Novel 3-[(2,4-Dinitrophenylamino)Alkyl] Derivatives of 5-Fluorouracil
  作者：Ali Khalaj、Khosrou Abdi、Seyed Nasser Ostad、Mohammad Reza Khoshayand、Navid Lamei、Hasan Ali Nedaie

  DOI：10.1111/cbdd.12211

  日期：2014.2

  Previously, it was reported that 3[3‐(2,4‐dinitrophenylamino)‐propyl]‐5‐fluorouracil 8c unlike its components 5‐fluorouracil (5‐FU) 6 and 2,4‐dinitroaniline 2 in HT‐29 cells under aerobic conditions had no cytotoxicity but showed radiosensitizing activity. In this study several analogues of 8c differing in the number of linking methylene groups were prepared and tested for in vitro cytotoxicity and

  以前，有报道称HT-29细胞中的3 [3-（2,4-二硝基苯氨基）-丙基] -5-氟尿嘧啶8c与它的成分5-氟尿嘧啶（5-FU）6和2,4-二硝基苯胺2不同。有氧条件没有细胞毒性，但表现出放射增敏活性。在这项研究中，制备了几种在连接亚甲基数量上不同的8c类似物，并测试了在有氧和低氧条件下的体外细胞毒性和放射增敏活性。通过5‐FU 6与多聚甲醛和2,4-二硝基苯胺2的反应在一个锅中制备栓系化合物8a在浓盐酸存在下，通过N-（溴代烷基）-2,4-二硝基苯胺5b-f与1-（叔丁氧羰基）-5-氟尿嘧啶7反应，然后水解制备化合物8b-f的保护基团。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）和碘化丙啶（PI）-洋地黄皂苷测定法和敏化增强比值（SER）来测定被测化合物的细胞毒性根据在不存在和存在每种敏化剂的情况下的放射存活曲线，分别测量37％的存活率，作为放射增敏活性的量