5-{[(1Z)-6-nitro-benzo[1,3]dioxol-5-yl-methylene]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione | 868962-57-6

• 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: 5-{[(1Z)-6-nitro-benzo[1,3]dioxol-5-yl-methylene]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
• 英文别名: 5-{[(1Z)-benzo([1,3]dioxol-6-nitro)-5-ylmethylene]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
• CAS: 868962-57-6
• 化学式: C₂₄H₂₀N₄O₆
• 分子量: 460.446
• InChiKey: ZLGWIWJHMVABMY-ROTLSHHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  114.58
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  5-{[(1Z)-6-nitro-benzo[1,3]dioxol-5-yl-methylene]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以1.09 g的产率得到5-{[benzo([1,3]dioxol-6-nitro)-5-ylmethyl]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
  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
• 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 、 甲苯 为溶剂， 反应 16.67h， 生成 5-{[(1Z)-6-nitro-benzo[1,3]dioxol-5-yl-methylene]amino}-N-2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinoline-1,3(2H)-dione
  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

• [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.