N-(3-dimethylamino-propyl)-4-nitro-1,8-naphthalimide | 92078-85-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3-dimethylamino-propyl)-4-nitro-1,8-naphthalimide
• 英文别名: 1h-Benz(de)isoquinoline-1,3(2h)-dione, 2-(3-(dimethylamino)propyl)-6-nitro-；2-[3-(dimethylamino)propyl]-6-nitrobenzo[de]isoquinoline-1,3-dione
• CAS: 92078-85-8
• 化学式: C₁₇H₁₇N₃O₄
• 分子量: 327.34
• InChiKey: HXUICTWMWMKWSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 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：
  86.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-硝基-1,8-萘醛酸酐 、 N,N-二甲基-1,3-二氨基丙烷 以 乙醇 为溶剂， 反应 0.25h， 生成 N-(3-dimethylamino-propyl)-4-nitro-1,8-naphthalimide
  参考文献：
  名称：

  A substituent constant analysis of the interaction of substituted naphthalene monoimides with DNA

  摘要：

  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.

  DOI：

  10.1021/jm00378a026

文献信息

• METHODS AND COMPOSITIONS FOR TREATING BETA-THALASSEMIA AND SICKLE CELL DISEASE
  申请人：ACADEMIA SINICA

  公开号：US20160106728A1

  公开（公告）日：2016-04-21

  Compounds, pharmaceutical compositions, and methods for treating anemia β-thalassemia anemia or sickle cell anemia.

  化合物、药物组合和治疗贫血β-地中海贫血或镰状细胞贫血的方法。
• 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：——
• US9662324B2
  申请人：——

  公开号：US9662324B2

  公开（公告）日：2017-05-30
• 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.