Methanesulfonamide, N-(4-(9-acridinylamino)-3-(methylamino)phenyl)- | 88412-78-6

• 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-(methylamino)phenyl)-
• 英文别名: N-[4-(acridin-9-ylamino)-3-(methylamino)phenyl]methanesulfonamide
• CAS: 88412-78-6
• 化学式: C₂₁H₂₀N₄O₂S
• 分子量: 392.481
• InChiKey: FODDJNZEXHBBKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  91.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methanesulfonamide, N-(4-(9-acridinylamino)-3-(methylamino)phenyl)- 在 manganese(IV) oxide 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 N-[4-[(E)-Acridin-9-ylimino]-3-methylamino-cyclohexa-2,5-dien-(E)-ylidene]-methanesulfonamide
  参考文献：
  名称：

  Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity

  摘要：

  Structure-activity relationships for a series of acridine-substituted 3'-N(CH3)2 derivatives of the clinical antileukemic drug amsacrine (1) are reported. The parent (unsubstituted) compound 3 has activity against the Lewis lung solid tumor that is superior to amsacrine (1), the new clinical amsacrine analogue 4, and the recently developed 3'-NHCH3 derivative 2. Although the compounds generally bind less well to DNA and are less dose potent in vivo than either their amsacrine (3'-OCH3) or 3'-NHCH3 analogues, they show very high levels of antitumor activity, with the 4-OCH3 derivative capable of effecting 100% cures of the Lewis lung solid tumor. The broad structure-activity relationships for acridine substitution more closely resemble those of the amsacrine than the 3'-NHCH3 series, with 4-substituted and 4,5-disubstituted compounds showing the highest activity.

  DOI：

  10.1021/jm00387a012
• 作为产物：
  描述：

  N-(3-chloro-4-nitrophenyl)methanesulfonamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 Methanesulfonamide, N-(4-(9-acridinylamino)-3-(methylamino)phenyl)-
  参考文献：
  名称：

  Potential antitumor agents. 41. Analogs of amsacrine with electron-donor substituents in the anilino ring

  摘要：

  The preparation and antitumor activity of a series of 3'-alkylamino and 3'-dialkylamino analogues of amsacrine are reported. The results support previous work suggesting that the presence of electron-donating groups in the 3'-position of the anilino ring substantially enhance the antitumor activity of amsacrine analogues, possibly by the provision of high levels of electron density at the 6'-position. The alkylamino derivatives generally possess tighter DNA binding, higher levels of in vitro and in vivo antileukemic activity, and greater aqueous solubility than the corresponding amsacrine analogues.

  DOI：

  10.1021/jm00369a022

文献信息

• Potential antitumor agents. 52. Carbamate analogs of amsacrine with in vivo activity against multidrug-resistant P388 leukemia
  作者：Gordon W. Rewcastle、Bruce C. Baguley、Graham J. Atwell、William A. Denny

  DOI：10.1021/jm00392a009

  日期：1987.9

  provided increased activity against the multidrug-resistant P388/ADR leukemia subline in vivo. Since activity against such resistant tumors is of great clinical significance, a series of acridine-substituted carbamate derivatives were evaluated against both wild-type and ADR/resistant P388 leukemia and the Lewis lung solid tumor in vivo. Structure-activity relationships for all three tumor lines were similar

  对一系列与抗白血病药物氨苯磺酸有关的苯胺取代的9-苯胺基cr啶的研究表明，1'-氨基甲酸酯基团在体内对多药耐药的P388 / ADR白血病亚系提供增强的活性。由于针对这种抗药性肿瘤的活性具有重要的临床意义，因此在体内针对野生型和ADR /抗药性P388白血病以及Lewis肺实体瘤评估了一系列of啶取代的氨基甲酸酯衍生物。所有三个肿瘤细胞系的结构活性关系相似，其中3-卤代-5-甲基和3-卤代5-甲氧基化合物被证明是活性最高的。这种取代模式还提供了最高的DNA结合。此类化合物（尤其是3-氯-5-甲基和3-氯-5-甲氧基）对野生型P388和Lewis肺具有体内活性，其活性与先前开发的最佳氨水analogue类似物相当（治愈率超过50％） ，以及P388 / ADR活动。这项工作从根本上完成了amsacrine系列抗肿瘤药的开发。