N-(6,7-methylenedioxyquinolin-4-yl)-N-[2-(tetrahydrofuran-2-yl)]-2-iodo-4,5-dimethoxybenzamide | 500214-48-2

• 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)-N-[2-(tetrahydrofuran-2-yl)]-2-iodo-4,5-dimethoxybenzamide
• 英文别名: N-(6,7-methylenedioxyquinolin-4-yl)-N-[2-(tetrahydrofuran-2-yl)methyl]-2-iodo-4,5-dimethoxybenzamide；N-([1,3]dioxolo[4,5-g]quinolin-8-yl)-2-iodo-4,5-dimethoxy-N-(oxolan-2-ylmethyl)benzamide
• CAS: 500214-48-2
• 化学式: C₂₄H₂₃IN₂O₆
• 分子量: 562.361
• InChiKey: KEQGAYFTGAJFNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(6,7-methylenedioxyquinolin-4-yl)-N-[2-(tetrahydrofuran-2-yl)]-2-iodo-4,5-dimethoxybenzamide 在 palladium diacetate 、 三(邻甲基苯基)磷 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以22%的产率得到8,9-dimethoxy-2,3-methylenedioxy-5-(2-tetrahydofuranyl)methyl-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：

  4,5-二甲氧基-2-碘苯甲酸 在 草酰氯 、 TEA 作用下， 以 二氯甲烷 为溶剂， 生成 N-(6,7-methylenedioxyquinolin-4-yl)-N-[2-(tetrahydrofuran-2-yl)]-2-iodo-4,5-dimethoxybenzamide
  参考文献：
  名称：

  Diaza- and triazachrysenes: potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435

  摘要：

  Several 5,12-diazachrysen-6-ones and 5,6,11-triazachrysen-12-ones were synthesized with varied substituents at the 5- or 11-position, respectively. Each compound was evaluated for its potential to stabilize the cleavable complex formed with TOP I and DNA. Two analogues with very potent TOP1-targeting activity, 3a and 4a, exhibited cytotoxic activity with IC50 values at or below 2 nM against RPM18402. Compound 3a was active in vivo by either ip or po administration in the human tumor xenograft athymic nude mice model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00737-0