12-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-2,3-dimethoxy-12H-8,10-dioxa-6,12-diaza-cyclopenta[b]chrysen-13-one | 529488-52-6

• 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: 12-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-2,3-dimethoxy-12H-8,10-dioxa-6,12-diaza-cyclopenta[b]chrysen-13-one
• CAS: 529488-52-6
• 化学式: C₂₅H₂₄N₂O₇
• 分子量: 464.475
• InChiKey: WPVFGGJBOVNZEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  90.27
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  12-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-2,3-dimethoxy-12H-8,10-dioxa-6,12-diaza-cyclopenta[b]chrysen-13-one 在 溶剂黄146 作用下， 反应 2.0h， 以60%的产率得到8,9-dimethoxy-2,3-methylenedioxy-5-[2,3-(dihydroxy)propyl]-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 palladium diacetate 、 草酰氯 、 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 15.75h， 生成 12-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-2,3-dimethoxy-12H-8,10-dioxa-6,12-diaza-cyclopenta[b]chrysen-13-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