Methanesulfonamide, N-(4-(9-acridinylamino)-3,5-dimethoxyphenyl)- | 86955-71-7

• 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: Methanesulfonamide, N-(4-(9-acridinylamino)-3,5-dimethoxyphenyl)-
• 英文别名: N-[4-(acridin-9-ylamino)-3,5-dimethoxyphenyl]methanesulfonamide
• CAS: 86955-71-7
• 化学式: C₂₂H₂₁N₃O₄S
• 分子量: 423.492
• InChiKey: DXABLRGASDXUSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  97.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-<(benzyloxycarbonyl)amino>-3,5-dimethoxymethanesulfonanilide 在 palladium on activated charcoal N-甲基吡咯烷酮 、 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 Methanesulfonamide, N-(4-(9-acridinylamino)-3,5-dimethoxyphenyl)-
  参考文献：
  名称：

  Potential antitumor agents. 39. Anilino ring geometry of amsacrine and derivatives: relationship to DNA binding and antitumor activity

  摘要：

  The clinical antileukemic drug amsacrine and analogues are thought to exert their biological activity by binding tightly but reversibly to DNA, with the acridine chromophore intercalated and the anilino group making additional binding contact in the minor groove of the double helix. In this binding model the steric environment around the 3'- and 5'-positions of the anilino ring is crucial. Two 3',5'-disubstituted analogues of amsacrine have been prepared, and their conformation, DNA binding properties, and antitumor activity were determined and compared with corresponding unsubstituted and 3'-substituted compounds. Addition of 3'- and 3',5'-substituents have little effect on minimum-energy conformations of the anilino side chain but have significant effects on DNA binding and biological activity. Monosubstitution lowers binding constants several-fold, but intercalative binding with extensive drug-base pair overlap is retained. Disubstitution lowers binding further, and although the binding is still intercalative as assessed by unwinding angles, it appears to occur with little drug-base pair overlap, as determined by high-field NMR studies of DNA imino proton shifts. These changes in DNA binding are accompanied by an abrupt change in biological activity, with the 3',5'-disubstituted analogues proving inactive and nontoxic even though other physicochemical properties, such as lipophilicity and stability, remain within acceptable limits. This study provides further evidence that the binding of drugs to DNA has a critical influence on their biological activity.

  DOI：

  10.1021/jm00365a014

文献信息

• Potential antitumor agents. 39. Anilino ring geometry of amsacrine and derivatives: relationship to DNA binding and antitumor activity
  作者：William A. Denny、Graham J. Atwell、Bruce C. Baguley

  DOI：10.1021/jm00365a014

  日期：1983.11

  The clinical antileukemic drug amsacrine and analogues are thought to exert their biological activity by binding tightly but reversibly to DNA, with the acridine chromophore intercalated and the anilino group making additional binding contact in the minor groove of the double helix. In this binding model the steric environment around the 3'- and 5'-positions of the anilino ring is crucial. Two 3',5'-disubstituted analogues of amsacrine have been prepared, and their conformation, DNA binding properties, and antitumor activity were determined and compared with corresponding unsubstituted and 3'-substituted compounds. Addition of 3'- and 3',5'-substituents have little effect on minimum-energy conformations of the anilino side chain but have significant effects on DNA binding and biological activity. Monosubstitution lowers binding constants several-fold, but intercalative binding with extensive drug-base pair overlap is retained. Disubstitution lowers binding further, and although the binding is still intercalative as assessed by unwinding angles, it appears to occur with little drug-base pair overlap, as determined by high-field NMR studies of DNA imino proton shifts. These changes in DNA binding are accompanied by an abrupt change in biological activity, with the 3',5'-disubstituted analogues proving inactive and nontoxic even though other physicochemical properties, such as lipophilicity and stability, remain within acceptable limits. This study provides further evidence that the binding of drugs to DNA has a critical influence on their biological activity.