5-Amino-2-[3-(dimethylamino)propyl]benzo[de]isoquinoline-1,3-dione | 69408-86-2

• 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: 5-Amino-2-[3-(dimethylamino)propyl]benzo[de]isoquinoline-1,3-dione
• CAS: 69408-86-2
• 化学式: C₁₇H₁₉N₃O₂
• 分子量: 297.357
• InChiKey: XMBVFUVBQQYJGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Amino-2-[3-(dimethylamino)propyl]benzo[de]isoquinoline-1,3-dione 、 N,N-二甲基-1,3-二氨基丙烷 在 nitrosonium tetrafluoroborate 作用下， 以 乙腈 、 乙醚 、 水 为溶剂， 反应 1.0h， 以58%的产率得到5,10-bis[3-(dimethylamino)propyl]benzo[de]triazolo[4,5-g]isoquinoline-4,6(5H,10H)-dione
  参考文献：
  名称：

  Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel triazolonaphthalimide derivatives

  摘要：

  An efficient synthesis method for fusing triazole ring onto the naphthalimide core was described. The anti-cancer activities of the generated triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The compounds generally displayed higher potency than amonafide. 4d,4e carrying two amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of 4a, was designed and synthesized. The agent was expected to be activated under the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower cytotoxicity both in cancer cell lines and human normal cells in the in vitro assays. However, N-oxide 5 performed potent anti-cancer activity in vivo using S-180 sarcoma bearing mice. All the results suggested that 5 was a promising anti-cancer agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.025
• 作为产物：
  描述：

  3-硝基-1,8-萘二甲酸酐 在 盐酸 、 tin(ll) chloride 作用下， 以 乙醇 、 水 为溶剂， 生成 5-Amino-2-[3-(dimethylamino)propyl]benzo[de]isoquinoline-1,3-dione
  参考文献：
  名称：

  Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel triazolonaphthalimide derivatives

  摘要：

  An efficient synthesis method for fusing triazole ring onto the naphthalimide core was described. The anti-cancer activities of the generated triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The compounds generally displayed higher potency than amonafide. 4d,4e carrying two amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of 4a, was designed and synthesized. The agent was expected to be activated under the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower cytotoxicity both in cancer cell lines and human normal cells in the in vitro assays. However, N-oxide 5 performed potent anti-cancer activity in vivo using S-180 sarcoma bearing mice. All the results suggested that 5 was a promising anti-cancer agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.025

文献信息

• Fernandez Brana; Martinez Sanz; Castellano, European Journal of Medicinal Chemistry, 1981, vol. 16, # 3, p. 207 - 212
  作者：Fernandez Brana、Martinez Sanz、Castellano、et al.

  DOI：——

  日期：——
• A substituent constant analysis of the interaction of substituted naphthalene monoimides with DNA
  作者：Karen A. Stevenson、Shau Fong Yen、Nai Chuang Yang、David W. Boykin、W. David Wilson

  DOI：10.1021/jm00378a026

  日期：1984.12

  In a continuing analysis of substituent effects in intercalator-DNA interactions, an unsubstituted naphthalene monoimide, with a 3-(dimethylamino)propyl group on the imide nitrogen has been prepared along with 3- and 4-nitro- and 3- and 4-amino-substituted derivatives. These derivatives allow an evaluation of the importance of the Hammett substituent constant and of the substituent position on the binding of naphthalene monoimides to DNA. Viscosity and spectrophotometric analyses indicate that all five compounds bind to DNA by intercalation. The 4-nitro compound gives a smaller viscosity increase and binds only approximately one-third as strongly as the 3-nitro derivative. It is postulated that this difference is due to the significant angle that the 4-nitro group makes with the intercalated monoimide ring system. The 3-NO2 group can assume a coplanar configuration with the monoimide ring system, allowing more favorable interactions with DNA base pairs, larger viscosity increases, and stronger binding to DNA. The binding constants of the 3-substituted monoimides are in the order 2 greater than 4 greater than 1 and, thus, do not follow a substituent constant pattern. The Tm values from thermal melting of DNA, on the other hand, are in the order 2 greater than 1 greater than 4, suggesting that the enthalpy contributions are significantly different for the binding of the three compounds to DNA. van't Hoff plots support this finding and indicate that both enthalpy and entropy contribute significantly to the binding free energy of 1 and 2 while the binding of 4 is primarily an enthalpic process. Plots of Tm and 65 degrees C log K values as a function of substituent constant for 1, 2, and 4 are linear. CPK model building studies suggest that 4 can form a hydrogen bond with the 5' diester oxygen of the sugar-phosphate backbone of DNA in an intercalation complex. This would lead to more favorable energetics of binding but a loss of mobility and/or available binding configurations with a resulting enthalpy-entropy compensation in the binding free energy of 4. This series of compounds dramatically illustrates the steric and hydrogen bonding complexity that can arise in attempts to design drugs to favorably interact with a DNA intercalation site as a potential bioreceptor.
• BRANA M. F.; SANZ A. M.; CASTELLANO J. M.; ROLDAN C. M.; ROLDAN C., EUR. J. MED. CHEM.-CHIM. THER., 1981, 16, NO 3, 207-212,
  作者：BRANA M. F.、 SANZ A. M.、 CASTELLANO J. M.、 ROLDAN C. M.、 ROLDAN C.

  DOI：——

  日期：——
• STEVENSON, K. A.;YEN, SHAU-FONG;YANG, NAI-CHUANG;BOYKIN, D. W.;WILSON, W.+, J. MED. CHEM., 1984, 27, N 12, 1677-1682
  作者：STEVENSON, K. A.、YEN, SHAU-FONG、YANG, NAI-CHUANG、BOYKIN, D. W.、WILSON, W.+

  DOI：——

  日期：——
• Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel triazolonaphthalimide derivatives
  作者：Shasha Li、Wenhe Zhong、Zhongjun Li、Xiangbao Meng

  DOI：10.1016/j.ejmech.2011.11.025

  日期：2012.1

  An efficient synthesis method for fusing triazole ring onto the naphthalimide core was described. The anti-cancer activities of the generated triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The compounds generally displayed higher potency than amonafide. 4d,4e carrying two amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of 4a, was designed and synthesized. The agent was expected to be activated under the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower cytotoxicity both in cancer cell lines and human normal cells in the in vitro assays. However, N-oxide 5 performed potent anti-cancer activity in vivo using S-180 sarcoma bearing mice. All the results suggested that 5 was a promising anti-cancer agent. (C) 2011 Elsevier Masson SAS. All rights reserved.