4-[N-[2-(t-butyldimethylsilanyloxy)]ethyl]amino-6,7-methylenedioxyquinoline | 529488-57-1

• 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: 4-[N-[2-(t-butyldimethylsilanyloxy)]ethyl]amino-6,7-methylenedioxyquinoline
• 英文别名: N-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-[1,3]dioxolo[4,5-g]quinolin-8-amine
• CAS: 529488-57-1
• 化学式: C₁₈H₂₆N₂O₃Si
• 分子量: 346.502
• InChiKey: UGEXHFQLBNTFCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[N-[2-(t-butyldimethylsilanyloxy)]ethyl]amino-6,7-methylenedioxyquinoline 在 palladium diacetate 、 三(邻甲基苯基)磷 草酰氯 、 silver carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 2,3-methylenedioxy-8,9-dimethoxy-5-[(2-hydroxy)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one
  参考文献：
  名称：

  [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES

  摘要：

  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。

  公开号：

  WO2012015875A1
• 作为产物：
  描述：

  8-羟基[1,3]二氧代lo[4,5-g]喹啉-7-羧酸乙酯 在 咪唑 、 potassium hydroxide 、 三氯氧磷 作用下， 以 二苯醚 、 乙醇 、 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 29.25h， 生成 4-[N-[2-(t-butyldimethylsilanyloxy)]ethyl]amino-6,7-methylenedioxyquinoline
  参考文献：
  名称：

  [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES

  摘要：

  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。

  公开号：

  WO2012015875A1

文献信息

• [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。
• 5H-Dibenzo[c,h]1,6-naphthyridin-6-ones: novel topoisomerase I-Targeting anticancer agents with potent cytotoxic activity
  作者：Alexander L. Ruchelman、Sudhir K. Singh、Abhijit Ray、Xiao Hua Wu、Jin-Ming Yang、Tsai-Kun Li、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/s0968-0896(03)00051-8

  日期：2003.5

  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.
• [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。