3,6-diazido-9-chloroacridine | 145531-28-8

• 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: 3,6-diazido-9-chloroacridine
• CAS: 145531-28-8
• 化学式: C₁₃H₆ClN₇
• 分子量: 295.691
• InChiKey: SMAYDXIXBMWOMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,6-diazido-9-chloroacridine 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 20.0~150.0 ℃ 、137.9 kPa 条件下， 反应 2.08h， 生成 4-pyrrolidin-1-yl-N-[6-(4-pyrrolidin-1-ylbutanoylamino)-9-[4-(3-pyrrolidin-1-ylpropanoylamino)anilino]acridin-3-yl]butanamide
  参考文献：
  名称：

  Trisubstituted Acridines as G-quadruplex Telomere Targeting Agents. Effects of Extensions of the 3,6- and 9-Side Chains on Quadruplex Binding, Telomerase Activity, and Cell Proliferation

  摘要：

  The synthesis is reported of a group of 3,6,9-trisubstituted acridine compounds as telomeric quadruplex-stabilizing ligands with systematic variations at the 3-, 6-, and 9-positions. A new microwave-assisted methodology has been developed for trisubstituted acridine synthesis. Structure-activity relationships are reported using surface plasmon resonance and a fluorescence melting assay to examine quadruplex binding, together with a telomerase inhibition assay. These reveal relationships between G-quadruplex stabilization and telomerase inhibition and optimal 3,6- and 9-substituent side-chain lengths for maximal activity. Qualitative molecular modeling using molecular dynamics simulations has been undertaken on four quadruplex-DNA complexes. Long-term exposure of MCF7 cancer cells to a subset of the most active compounds, at doses lower than the IC50 values, showed that one compound produced a marked decrease in population growth, accompanied by senescence, which is consistent with telomere targeting by this agent.

  DOI：

  10.1021/jm050555a
• 作为产物：
  描述：

  3,6-二氨基-9-吖啶酮 在 氯化亚砜 、 sodium azide 、 硫酸 、 sodium nitrite 作用下， 生成 3,6-diazido-9-chloroacridine
  参考文献：
  名称：

  Trisubstituted Acridines as G-quadruplex Telomere Targeting Agents. Effects of Extensions of the 3,6- and 9-Side Chains on Quadruplex Binding, Telomerase Activity, and Cell Proliferation

  摘要：

  The synthesis is reported of a group of 3,6,9-trisubstituted acridine compounds as telomeric quadruplex-stabilizing ligands with systematic variations at the 3-, 6-, and 9-positions. A new microwave-assisted methodology has been developed for trisubstituted acridine synthesis. Structure-activity relationships are reported using surface plasmon resonance and a fluorescence melting assay to examine quadruplex binding, together with a telomerase inhibition assay. These reveal relationships between G-quadruplex stabilization and telomerase inhibition and optimal 3,6- and 9-substituent side-chain lengths for maximal activity. Qualitative molecular modeling using molecular dynamics simulations has been undertaken on four quadruplex-DNA complexes. Long-term exposure of MCF7 cancer cells to a subset of the most active compounds, at doses lower than the IC50 values, showed that one compound produced a marked decrease in population growth, accompanied by senescence, which is consistent with telomere targeting by this agent.

  DOI：

  10.1021/jm050555a

文献信息

• Synthesis and in vitro Evaluation of 9-Anilino-3,6-diaminoacridines Active Against a Multidrug-Resistant Strain of the Malaria Parasite Plasmodium falciparum
  作者：Swarna A. Gamage、Nisana Tepsiri、Prapon Wilairat、Stanley J. Wojcik、David P. Figgitt、Raymond K. Ralph、William A. Denny

  DOI：10.1021/jm00036a014

  日期：1994.5

  A new synthesis of 3,6-diamino-9-anilinoacridines, via reduction of the corresponding diazides, gives much higher yields than traditional methods. Within the subset of 3,6-diamino-9-anilinoacridines, there was considerable tolerance to substitution at the 1'-anilino position. In a sharp divergence with structure-activity relationships for high mammalian cell toxicity and anticancer effects, derivatives

  已经制备了一系列9-苯胺基oa啶酮，并评估了它们对红细胞悬液中疟原虫恶性疟原虫的多药耐药K1株的活性。与其他取代方式相比，啶环上的3,6-二氨基取代导致较低的哺乳动物细胞细胞毒性和较高的抗寄生虫活性，从而提供具有最高体外治疗指数的化合物。通过还原相应的叠氮化物，新合成3,6-二氨基-9-苯胺基cr啶的产率比传统方法高得多。在3，6-二氨基-9-苯胺基cr啶的子集中，对1'-苯胺基位置的取代具有相当大的耐受性。在具有高哺乳动物细胞毒性和抗癌作用的构效关系方面，带有吸电子1'取代基的衍生物（例如SO2-NHR和CONHR）显示出最有效的抗疟活性（IC50值为10-20 nM）。代表性的化合物显示出是人类拓扑异构酶II的DNA链传递活性和相应寄生虫DNA脱链活性的有效抑制剂。1'-SO2NH2衍生物7n在20 microM时完全抑制了Jurkat拓扑异构酶II的链通过，并且在1 microM或以