2-(4-methoxyphenyl)-N-{2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}acetamide

• 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-(4-methoxyphenyl)-N-{2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}acetamide
• 英文别名: 2-(4-methoxyphenyl)-N-{2-[2-(dimethyl-amino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}acetamide；N-[2-[2-(dimethylamino)ethyl]-1,3-dioxobenzo[de]isoquinolin-5-yl]-2-(4-methoxyphenyl)acetamide
• 化学式: C₂₅H₂₅N₃O₄
• 分子量: 431.491
• InChiKey: YTQOMKQMSYYYRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  米托萘胺 在 palladium on activated charcoal 甲酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 1.67h， 生成 2-(4-methoxyphenyl)-N-{2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}acetamide
  参考文献：
  名称：

  2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity

  摘要：

  Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase II alpha, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.

  DOI：

  10.1021/jm070315q

文献信息

• NAPTHALIMIDE DERIVATIVES, METHODS FOR THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS THEREFROM
  申请人：VAN QUAQUEBEKE Eric

  公开号：US20070117836A1

  公开（公告）日：2007-05-24

  Novel substituted naphthalimide derivatives, pharmaceutically acceptable salts thereof and solvates thereof, are useful for making pharmaceutical compositions for the treatment of cell proliferative diseases such as cancer. The invention also provides methods for making such derivatives.

  本发明提供了替代萘酰亚胺衍生物的新型，其药学上可接受的盐和溶剂化物，用于制备治疗细胞增殖性疾病，如癌症的药物组合物。本发明还提供了制备这种衍生物的方法。
• [EN] NAPHTHALIMIDE DERIVATIVES FOR THE TREATMENT OF CANCER<br/>[FR] DERIVES NAPHTHALIMIDES, PROCEDES DE FABRICATION ET COMPOSITIONS PHARMACEUTIQUES LES RENFERMANT
  申请人：UNIBIOSCREEN SA

  公开号：WO2005105753A3

  公开（公告）日：2006-02-02
• 2,2,2-Trichloro-<i>N</i>-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1<i>H</i>-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity
  作者：Eric Van Quaquebeke、Tine Mahieu、Patrick Dumont、Janique Dewelle、Fabrice Ribaucour、Gentiane Simon、Sébastien Sauvage、Jean-François Gaussin、Jérôme Tuti、Mohamed El Yazidi、Frank Van Vynckt、Tatjana Mijatovic、Florence Lefranc、Francis Darro、Robert Kiss

  DOI：10.1021/jm070315q

  日期：2007.8.1

  Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase II alpha, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-(2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.