1-(3-methoxyphenyl)-3-(4-((3-nitroacridin-9-yl)amino)phenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(3-methoxyphenyl)-3-(4-((3-nitroacridin-9-yl)amino)phenyl)urea
• 英文别名: 1-(3-Methoxyphenyl)-3-[4-[(3-nitroacridin-9-yl)amino]phenyl]urea；1-(3-methoxyphenyl)-3-[4-[(3-nitroacridin-9-yl)amino]phenyl]urea
• 化学式: C₂₇H₂₁N₅O₄
• 分子量: 479.495
• InChiKey: AGLJMYSSGICCDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-anilino-4-nitrobenzoic acid 在 盐酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 1-(3-methoxyphenyl)-3-(4-((3-nitroacridin-9-yl)amino)phenyl)urea
  参考文献：
  名称：

  Design, synthesis and evaluation of acridine derivatives as multi-target Src and MEK kinase inhibitors for anti-tumor treatment

  摘要：

  Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 mu M, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure-activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.011

文献信息

• Design, synthesis and evaluation of acridine derivatives as multi-target Src and MEK kinase inhibitors for anti-tumor treatment
  作者：Zhishan Cui、Xi Li、Lulu Li、Bin Zhang、Chunmei Gao、Yuzong Chen、Chunyan Tan、Hongxia Liu、Weiyi Xie、Ti Yang、Yuyang Jiang

  DOI：10.1016/j.bmc.2015.12.011

  日期：2016.1

  Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 mu M, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure-activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.