1-[2-[N-(6,7-methylenedioxyquinolin-4-yl)]amino]ethylpyrrolidine | 529488-49-1

• 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-[2-[N-(6,7-methylenedioxyquinolin-4-yl)]amino]ethylpyrrolidine
• 英文别名: N-(2-pyrrolidin-1-ylethyl)-[1,3]dioxolo[4,5-g]quinolin-8-amine
• CAS: 529488-49-1
• 化学式: C₁₆H₁₉N₃O₂
• 分子量: 285.346
• InChiKey: XMIFCKFUILAXAX-UHFFFAOYSA-N

物化性质

• 沸点：
  480.7±45.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  46.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-[N-(6,7-methylenedioxyquinolin-4-yl)]amino]ethylpyrrolidine 在 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 8,9-dimethoxy-2,3-methylenedioxy-5-[2-(pyrrolidin-1-yl)ethyl]-5H-dibenzo[c,h]1,6-naphthyridin-6-one
  参考文献：
  名称：

  5H-Dibenzo[c,h]1,6-naphthyridin-6-ones: novel topoisomerase I-Targeting anticancer agents with potent cytotoxic activity

  摘要：

  5H-Dibenzo[c,h]1,6-naphthyridine-6-ones can exhibit potent antitumor activity. The effect of varied substituents at the 5-position of 5H-8,9-dimethoxy-2,3-methylenedioxydibenzo[c,h]1,6-naphthyridine on relative cytotoxicity and topoisomerase 1-targeting activity was evaluated. Potent TOP-1-targeting activity is observed when the 5-position is substituted with either a 2-(N,N-dimethylamino)ethyl group, as in 3a, or a 2-(pyrrolidin-1-yl)ethyl substituent, 3c. In contrast, the addition of a beta-methyl group or a beta-hydroxymethyl group to compound 3a, as in 3b and 3j, results in a loss of significant TOP1-targeting activity. While the presence of a 3-(N,N-dimethylamino)propyl substituent at the 5-position or a methyl(2-tetrahydrofuranyl) group allows for retention of TOP1-targeting activity, the 2-(4-methyl-1-piperazinyl)ethyl analogue, 3d, did not exhibit significant activity. Replacement of the N,N-dimethylamino group of 3a with either C2H5 or OH, as in 3f and 3h, respectively, also had a negative impact on both cytotoxicity and TOP1-targeting activity. Treatment of 3a with LAH gave the 5,6-dihydrodibenzo[c,h]naphthyridine, 4a. This dihydro derivative has approximately 2/3 the potency of 3a as a TOP1-targeting agent. Compounds 3a, 3b, 3h, 3i, and 4a were evaluated for antitumor activity in the human tumor xenograft model using athymic nude mice. The non-estrogen responsive breast tumor cell line, MDA-MB-435, was used in these assays. Compound 3a proved to be effective in regressing tumor growth in vivo when administered either by ip injection or orally 3x week at a dose of 2.0 mg/kg. Compound 4a when administered orally 5x weekly at a dose of 40 mg/kg also suppressed tumor growth. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00051-8
• 作为产物：
  描述：

  6,7-methylenedioxy-4-quinolone 在 苯酚 作用下， 反应 22.5h， 生成 1-[2-[N-(6,7-methylenedioxyquinolin-4-yl)]amino]ethylpyrrolidine
  参考文献：
  名称：

  5H-Dibenzo[c,h]1,6-naphthyridin-6-ones: novel topoisomerase I-Targeting anticancer agents with potent cytotoxic activity

  摘要：

  5H-Dibenzo[c,h]1,6-naphthyridine-6-ones can exhibit potent antitumor activity. The effect of varied substituents at the 5-position of 5H-8,9-dimethoxy-2,3-methylenedioxydibenzo[c,h]1,6-naphthyridine on relative cytotoxicity and topoisomerase 1-targeting activity was evaluated. Potent TOP-1-targeting activity is observed when the 5-position is substituted with either a 2-(N,N-dimethylamino)ethyl group, as in 3a, or a 2-(pyrrolidin-1-yl)ethyl substituent, 3c. In contrast, the addition of a beta-methyl group or a beta-hydroxymethyl group to compound 3a, as in 3b and 3j, results in a loss of significant TOP1-targeting activity. While the presence of a 3-(N,N-dimethylamino)propyl substituent at the 5-position or a methyl(2-tetrahydrofuranyl) group allows for retention of TOP1-targeting activity, the 2-(4-methyl-1-piperazinyl)ethyl analogue, 3d, did not exhibit significant activity. Replacement of the N,N-dimethylamino group of 3a with either C2H5 or OH, as in 3f and 3h, respectively, also had a negative impact on both cytotoxicity and TOP1-targeting activity. Treatment of 3a with LAH gave the 5,6-dihydrodibenzo[c,h]naphthyridine, 4a. This dihydro derivative has approximately 2/3 the potency of 3a as a TOP1-targeting agent. Compounds 3a, 3b, 3h, 3i, and 4a were evaluated for antitumor activity in the human tumor xenograft model using athymic nude mice. The non-estrogen responsive breast tumor cell line, MDA-MB-435, was used in these assays. Compound 3a proved to be effective in regressing tumor growth in vivo when administered either by ip injection or orally 3x week at a dose of 2.0 mg/kg. Compound 4a when administered orally 5x weekly at a dose of 40 mg/kg also suppressed tumor growth. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00051-8

文献信息

• [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES<br/>[FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES
  申请人：GENZYME CORP

  公开号：WO2012015875A1

  公开（公告）日：2012-02-02

  The invention provides methods and pharmaceutical compositions for treating certain hematological cancers.

  这项发明提供了治疗特定血液系统癌症的方法和药物组合物。
• [EN] METHODS FOR TREATING GASTRIC AND PANCREATIC MALIGNANCIES<br/>[FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS GASTRIQUES ET PANCRÉATIQUES
  申请人：GENZYME CORP

  公开号：WO2012015901A1

  公开（公告）日：2012-02-02

  The invention provides methods and pharmaceutical compositions for treating pancreatic cancer or gastric cancer or a metastasis thereof.

  该发明提供了治疗胰腺癌或胃癌或其转移的方法和药物组合物。
• Solubilized topoisomerase poisons
  申请人：LaVoie J. Edmond

  公开号：US20050009824A1

  公开（公告）日：2005-01-13

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.

  本发明提供了I式化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及其药学上可接受的盐。本发明还提供了包含I式化合物的制药组合物，制备I式化合物的过程，用于制备I式化合物的中间体，以及使用I式化合物治疗癌症的治疗方法。
• SOLUBILIZED TOPOISOMERASE POISONS
  申请人：LaVoie Edmond J.

  公开号：US20090239871A1

  公开（公告）日：2009-09-24

  The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.

  该发明提供了公式I的化合物：其中A、B、W、Y、Z和R1具有规范中定义的任何含义，以及它们的药学上可接受的盐。该发明还提供了包括公式I化合物的药物组合物、用于制备公式I化合物的中间体以及使用公式I化合物治疗癌症的治疗方法。
• METHODS TO TREAT CANCER
  申请人：Lavoie Edmond J.

  公开号：US20120004235A1

  公开（公告）日：2012-01-05

  The invention provides methods and pharmaceutical compositions for treating certain cancers with compounds of formula (I) wherein A, B, W, Y, Z, and R 1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts and prodrugs.

  本发明提供了使用式(I)的化合物的方法和制药组合物，用于治疗某些癌症，其中A，B，W，Y，Z和R1具有规范中定义的任何含义，以及它们的药学上可接受的盐和前药。