N-(6,7-methylenedioxyquinolin-4-yl)butylamine | 528879-62-1

• 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: N-(6,7-methylenedioxyquinolin-4-yl)butylamine
• 英文别名: N-butyl-[1,3]dioxolo[4,5-g]quinolin-8-amine
• CAS: 528879-62-1
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: DJGUCVFYZJALCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  43.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6,7-methylenedioxyquinolin-4-yl)butylamine 在 palladium diacetate 、 Ra-Ni 、 一水合肼 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.0h， 生成 8-amino-5-butyl-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
  参考文献：
  名称：

  Nitro and Amino Substitution in the D-Ring of 5-(2-Dimethylaminoethyl)- 2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-ones:  Effect on Topoisomerase-I Targeting Activity and Cytotoxicity

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one exhibits potent TOP1-targeting activity and pronounced antitumor activity. It was hypothesized that replacement of the two methoxyl groups with a nitro substituent would allow for retention of similar activity. In this study 8-, 9-, and 10-nitro-5H-2,3-methylenedioxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h] [1,6]naphthyridin-6-one and their amino derivatives were synthesized and assessed for their relative TOP1-targeting activity and cytotoxicity. In the case of both the 8- and 9-nitro analogues, their TOP1-targeting activity and cytotoxicity are greater than that of camptothecin and comparable to that of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one.

  DOI：

  10.1021/jm020498a
• 作为产物：
  描述：

  6,7-methylenedioxy-4-quinolone 在 苯酚 作用下， 反应 26.5h， 生成 N-(6,7-methylenedioxyquinolin-4-yl)butylamine
  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

• Cytotoxic agents
  申请人：LaVoie J. Edmond

  公开号：US20050009825A1

  公开（公告）日：2005-01-13

  The invention provides compounds of the invention pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  本发明提供了本发明的化合物、包含本发明化合物的制药组合物、制备本发明化合物的方法、制备本发明化合物有用的中间体以及治疗癌症和其他拓扑异构酶介导病症的治疗方法。
• CYTOTOXIC AGENTS
  申请人：LaVoie J. Edmond

  公开号：US20080090831A1

  公开（公告）日：2008-04-17

  The invention provides compounds of the invention pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

  该发明提供了化合物的发明，包括化合物的制药组合物，制备化合物的过程，用于制备化合物的中间体以及治疗癌症和其他拓扑异构酶介导疾病的治疗方法。
• Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones
  作者：Lisa Sharma、Yuan-Chin Tsai、Angela A. Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.ejmech.2008.09.048

  日期：2009.4

  Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent. (C) 2008 Elsevier Masson SAS. All rights reserved.
• US7319105B2
  申请人：——

  公开号：US7319105B2

  公开（公告）日：2008-01-15
• US7468366B2
  申请人：——

  公开号：US7468366B2

  公开（公告）日：2008-12-23