2-(3-(dimethylamino)propyl)-6-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione | 1207670-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-(3-(dimethylamino)propyl)-6-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione
• 英文别名: 2-[3-(Dimethylamino)propyl]-6-(methylamino)benzo[de]isoquinoline-1,3-dione
• CAS: 1207670-54-9
• 化学式: C₁₈H₂₁N₃O₂
• 分子量: 311.384
• InChiKey: FRDWEKCFJBQNQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-bromo-N-(N,N-dimethyl)propylamino-1,8-naphthalimide 、 甲胺 在 copper(ll) sulfate pentahydrate 作用下， 以 水 为溶剂， 反应 4.0h， 以86%的产率得到2-(3-(dimethylamino)propyl)-6-(methylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis

  摘要：

  Based on the advantages of multitarget drugs for cancer treatment, a new class of naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), and ultimately caused apoptosis and cell death. The majority of compounds 7a-d and 8a-d potently inhibited the growth of the five tested cancer cell lines with IC(50) values ranging from 2 to 10 mu M and are more active than amonafide, a naphthahmide that was in phase III clinical trials. These compounds were tested for their interactions with DNA and their cell-free topo II inhibition activities, which demonstrated these compounds were weak DNA binders but modest topo II inhibitors. Furthermore, compounds 7b-d were found to notably induce LMP and exhibited better antiproliferative activity compared with their single-target analogues. All of the newly synthesized compounds were demonstrated to efficiently induce apoptosis via a mitochondrial pathway. Accordingly, a new paradigm was suggested for the design of novel multitarget anticancer drugs.

  DOI：

  10.1021/jm100025u

文献信息

• A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis
  作者：Zhuo Chen、Xin Liang、Huanying Zhang、Hua Xie、Jianwen Liu、Yufang Xu、Weiping Zhu、Yi Wang、Xin Wang、Shaoying Tan、Dong Kuang、Xuhong Qian

  DOI：10.1021/jm100025u

  日期：2010.3.25

  Based on the advantages of multitarget drugs for cancer treatment, a new class of naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), and ultimately caused apoptosis and cell death. The majority of compounds 7a-d and 8a-d potently inhibited the growth of the five tested cancer cell lines with IC(50) values ranging from 2 to 10 mu M and are more active than amonafide, a naphthahmide that was in phase III clinical trials. These compounds were tested for their interactions with DNA and their cell-free topo II inhibition activities, which demonstrated these compounds were weak DNA binders but modest topo II inhibitors. Furthermore, compounds 7b-d were found to notably induce LMP and exhibited better antiproliferative activity compared with their single-target analogues. All of the newly synthesized compounds were demonstrated to efficiently induce apoptosis via a mitochondrial pathway. Accordingly, a new paradigm was suggested for the design of novel multitarget anticancer drugs.