3,6-diamino-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine | 875924-03-1

• 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-diamino-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine
• 英文别名: N-[4-[(3,6-diaminoacridin-9-yl)amino]phenyl]-3-pyrrolidin-1-ylpropanamide
• CAS: 875924-03-1
• 化学式: C₂₆H₂₈N₆O
• 分子量: 440.548
• InChiKey: ZGMYSFYZBBFUKG-UHFFFAOYSA-N

物化性质

• 熔点：
  205-210 °C
• 沸点：
  745.8±60.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,6-diamino-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 0.08h， 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 palladium on activated charcoal 盐酸 、 氯化亚砜 、 sodium azide 、 硫酸 、 氢气 、 sodium nitrite 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、137.9 kPa 条件下， 反应 2.0h， 生成 3,6-diamino-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine
  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