2,2,2-trichloro-N-[({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}amino)carbonyl]acetamide | 868962-26-9

• 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: 2,2,2-trichloro-N-[({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}amino)carbonyl]acetamide
• 英文别名: 2,2,2-trichloro-N-[[2-[2-(dimethylamino)ethyl]-1,3-dioxobenzo[de]isoquinolin-5-yl]carbamoyl]acetamide
• CAS: 868962-26-9
• 化学式: C₁₉H₁₇Cl₃N₄O₄
• 分子量: 471.727
• InChiKey: BZXLHTMMVVPPAF-UHFFFAOYSA-N

物化性质

• 密度：
  1.550±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloro-N-[({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}amino)carbonyl]acetamide 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 以72%的产率得到2,2,2-trichloro-N-[({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}amino)carbonyl]acetamide hydrochloride
  参考文献：
  名称：

  [EN] NAPHTHALIMIDE DERIVATIVES FOR THE TREATMENT OF CANCER
  [FR] DERIVES NAPHTHALIMIDES, PROCEDES DE FABRICATION ET COMPOSITIONS PHARMACEUTIQUES LES RENFERMANT

  摘要：

  公开号：

  WO2005105753A3
• 作为产物：
  描述：

  3-硝基-1,8-萘二甲酸酐 在 palladium on activated charcoal 甲酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 5.67h， 生成 2,2,2-trichloro-N-[({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}amino)carbonyl]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

• 5-Urea Substituted Naphthalimide Derivatives, Methods of Production and Pharmaceutical Compositions for Treating Cancer
  申请人：Van Quaquebeke Eric

  公开号：US20090118321A1

  公开（公告）日：2009-05-07

  Novel ureyl-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 through hydrolysis of known compounds.

  新型的尿素取代萘酰亚胺衍生物及其药学上可接受的盐和溶剂，可用于制备治疗细胞增殖性疾病如癌症的药物组合物。该发明还提供了通过已知化合物的水解制备这种衍生物的方法。
• Compositions and methods for treatment of prostate and breast cancer
  申请人：Van Quaquebeke Eric

  公开号：US20090221628A1

  公开（公告）日：2009-09-03

  Novel ureyl-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 of treating specific types of cancer such as prostate, esophageal, glioblastoma, gliosarcoma, NSCLC, head and neck, and breast with the compounds described herein alone and in combination with antineoplastic agents.

  新颖的尿素取代的萘酰亚胺衍生物，其药学上可接受的盐和溶剂化物，可用于制备用于治疗细胞增殖性疾病如癌症的药物组合物。该发明还提供了使用本文所述化合物单独或与抗肿瘤药物联合治疗前列腺癌、食道癌、胶质母细胞瘤、胶质肉瘤、非小细胞肺癌、头颈癌和乳腺癌等特定类型癌症的方法。
• Compositions and methods for treatment of esophageal cancer
  申请人：Van Quaquebeke Eric

  公开号：US20090232907A1

  公开（公告）日：2009-09-17

  Novel ureyl-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 of treating specific types of cancer such as prostate, esophageal, glioblastoma, gliosarcoma, NSCLC, head and neck, and breast with the compounds described herein alone and in combination with antineoplastic agents.

  新型尿素基取代萘酰亚胺衍生物及其药学上可接受的盐和溶剂化物，可用于制备用于治疗细胞增殖性疾病，如癌症的药物组合物。本发明还提供了使用本文描述的化合物单独或与抗肿瘤剂联合治疗特定类型的癌症，如前列腺癌、食管癌、胶质母细胞瘤、胶质肉瘤、非小细胞肺癌、头颈部和乳腺癌的方法。
• 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。
• SMALL MOLECULE MODIFIERS OF MICRORNA MIR-122
  申请人：Deiters Alexander

  公开号：US20130005759A1

  公开（公告）日：2013-01-03

  MicroRNAs are a class of endogenous regulators of gene function. Aberrant regulation of microRNAs has been linked to various human diseases, most importantly cancer. Small molecule intervention of microRNA misregulation has the potential to provide new therapeutic approaches to such diseases. microRNA miR-122 is the most abundant microRNA in the liver and is involved in hepatocellular carcinoma development and hepatitis C virus (HCV) infection. Small molecule inhibitors and activators of the microRNA miR-122 are described, and methods for their identification are reported. These small molecule inhibitors reduce viral replication in liver cells and thus represent a new approach to the treatment of HCV infections. Moreover, small molecule activation of miR-122 in liver cancer cells selectively induced apoptosis through caspase activation, and thus has implications in cancer chemotherapy.

  MicroRNAs是一类内源性基因调控因子。微小RNA的异常调控已与各种人类疾病，尤其是癌症相关联。小分子干预微小RNA的错调可能为这些疾病提供新的治疗方法。微小RNA miR-122是肝脏中最丰富的微小RNA，参与肝细胞癌的发展和丙型肝炎病毒（HCV）感染。描述了微小RNA miR-122的小分子抑制剂和激活剂，并报道了其鉴定方法。这些小分子抑制剂能够减少肝细胞中的病毒复制，因此代表了治疗HCV感染的新方法。此外，小分子激活miR-122在肝癌细胞中选择性地通过caspase激活诱导凋亡，因此在癌症化疗中具有重要意义。