N-[4-(9-吖啶基氨基)-3-(二甲基氨基)苯基]甲烷磺酰胺 | 88412-94-6

• 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
• 中文名称: N-[4-(9-吖啶基氨基)-3-(二甲基氨基)苯基]甲烷磺酰胺
• 中文别名: (1S,2R,3S,5S)-3-(4-氨基-7H-吡咯并[2,3-d]嘧啶-7-基)-5-(羟甲基)环戊烷-1,2-二醇
• 英文名称: 9-(2-dimethylamino-4-methylsulphonylaminoanilino)acridinium
• 英文别名: Methanesulfonamide, N-(4-(9-acridinylamino)-3-(dimethylamino)phenyl)-；N-[4-(acridin-9-ylamino)-3-(dimethylamino)phenyl]methanesulfonamide
• CAS: 88412-94-6
• 化学式: C₂₂H₂₂N₄O₂S
• 分子量: 406.508
• InChiKey: JCZWUYIXVYHWDE-UHFFFAOYSA-N

物化性质

• 沸点：
  572.0±60.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  82.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[4-(9-吖啶基氨基)-3-(二甲基氨基)苯基]甲烷磺酰胺 在 manganese(IV) oxide 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以92%的产率得到Methanesulfonamide,N-[4-(9-acridinylimino)-3-(dimethylamino)-2,5-cyclohexadien-1-ylidene]-
  参考文献：
  名称：

  9-苯胺基cr啶类抗肿瘤剂的氧化还原化学。

  摘要：

  在苯胺环上带有1'-NHR取代基的9-苯胺基r啶容易进行化学可逆的两电子氧化，生成醌二亚胺。已经研究了三组9-苯胺基cr啶酮（1'-取代的衍生物，以及临床抗白血病药物Amsacrine的3'-取代的类似物和cr啶取代的类似物）的化学和电化学氧化作用，并确定了它们的氧化还原电位。对于苯胺取代的衍生物，氧化还原电势（E1 / 2）与取代基的电子特性密切相关，而供电子的取代基则有助于氧化。cr啶环中的取代基对氧化还原电势几乎没有影响，表明从effects啶到苯胺环的电子效应传递最小。尽管9-苯胺基lin啶类化合物在很宽的结构变化范围内均显示出生物学活性，但1'-NHR取代基是活性最高的衍生物的共同特征。然而，在氧化还原电势与生物活性之间尚无明确的定量关系，并且该氧化还原化学与氨ac碱和其他9-苯胺基cr啶的作用方式之间的相关性仍不清楚。

  DOI：

  10.1021/jm00386a006
• 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， 反应 12.0h， 生成 N-[4-(9-吖啶基氨基)-3-(二甲基氨基)苯基]甲烷磺酰胺
  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。
• One-electron redox chemistry of amsacrine, mAMSA [9-(2-methoxy-4-methylsulphonylaminoanilino)acridinium], its quinone di-imine, and an analogue. A radiolytic study
  作者：Robert F. Anderson、John E. Packer、William A. Denny

  DOI：10.1039/p29880000489

  日期：——

  The redox chemistry of the clinical antileukemia drug mAMSA (amsacrine) and of its dimethylamino analogue (diAMSA) has been investigated by radiolytic methods. Steady-state and pulse radiolysis experiments show that upon one-electron oxidation both compounds give quinone di-imine radicals (mAQDI˙ and diAQDI˙) which disproportionate to the parent compounds and the corresponding quinone di-imines (mAQDI

  临床抗白血病药物mAMSA（氨苯uk碱）及其二甲氨基类似物（diAMSA）的氧化还原化学已通过放射分解方法进行了研究。稳态和脉冲辐射分解实验表明，单电子氧化后，两种化合物都会生成与母体化合物和相应的醌二亚胺（mAQDI和diAQDI）不成比例的醌二亚胺基团（mAQDI˙和diAQDI˙）。醌二亚胺的单电子还原得到相同的中间基团，该中间基团未被氧氧化。纳秒脉冲辐射分解实验表明，醌二亚胺的初始单电子还原也发生在the啶环上，但随后分子内电子迅速转移至醌二亚胺侧链。mAMSA的单电子还原发生在cr啶环上，并导致形成cri啶。mAMSA–mAQDI˙对在pH 7.4时的氧化还原电势计算为915 mV（与nhe相比），而mAMSA–mAQDI对的氧化还原电势为415 mV。类似的diAMSA显示出相似的可逆氧化还原化学反应，但更易于氧化，计算得出的氧化还原电位diAMSA–diAQDI˙为635 m
• Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity
  作者：Graham J. Atwell、Gordon W. Rewcastle、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00387a012

  日期：1987.4

  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.
• Redox chemistry of the 9-anilinoacridine class of antitumor agents
  作者：Jeffrey L. Jurlina、Andrew Lindsay、John E. Packer、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00386a006

  日期：1987.3

  on the anilino ring undergo facile, chemically reversible, two-electron oxidation to quinone diimines. The chemical and electrochemical oxidation of three groups of 9-anilinoacridines (1'-substituted derivatives, together with 3'-substituted analogues and acridine-substituted analogues of the clinical antileukemic drug amsacrine) have been studied and their redox potentials determined. For aniline-substituted

  在苯胺环上带有1'-NHR取代基的9-苯胺基r啶容易进行化学可逆的两电子氧化，生成醌二亚胺。已经研究了三组9-苯胺基cr啶酮（1'-取代的衍生物，以及临床抗白血病药物Amsacrine的3'-取代的类似物和cr啶取代的类似物）的化学和电化学氧化作用，并确定了它们的氧化还原电位。对于苯胺取代的衍生物，氧化还原电势（E1 / 2）与取代基的电子特性密切相关，而供电子的取代基则有助于氧化。cr啶环中的取代基对氧化还原电势几乎没有影响，表明从effects啶到苯胺环的电子效应传递最小。尽管9-苯胺基lin啶类化合物在很宽的结构变化范围内均显示出生物学活性，但1'-NHR取代基是活性最高的衍生物的共同特征。然而，在氧化还原电势与生物活性之间尚无明确的定量关系，并且该氧化还原化学与氨ac碱和其他9-苯胺基cr啶的作用方式之间的相关性仍不清楚。
• Potential antitumor agents. 41. Analogs of amsacrine with electron-donor substituents in the anilino ring
  作者：Graham J. Atwell、Gordon W. Rewcastle、William A. Denny、Bruce F. Cain、Bruce C. Baguley

  DOI：10.1021/jm00369a022

  日期：1984.3

  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.