3,6-bis[5-(pyrrolidin-1-yl)pentanamido]-9-chloroacridine | 875923-88-9

• 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-bis[5-(pyrrolidin-1-yl)pentanamido]-9-chloroacridine
• 英文别名: N-[9-chloro-6-(5-pyrrolidin-1-ylpentanoylamino)acridin-3-yl]-5-pyrrolidin-1-ylpentanamide
• CAS: 875923-88-9
• 化学式: C₃₁H₄₀ClN₅O₂
• 分子量: 550.144
• InChiKey: HYBINYKNKVGGAV-UHFFFAOYSA-N

物化性质

• 沸点：
  814.1±65.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,6-bis[5-(pyrrolidin-1-yl)pentanamido]-9-chloroacridine 、 4-dimethylaminophenylamine dihydrochloride 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以12 mg的产率得到5-Pyrrolidin-1-yl-pentanoic acid [9-(4-dimethylamino-phenylamino)-6-(5-pyrrolidin-1-yl-pentanoylamino)-acridin-3-yl]-amide
  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：

  5-氯代戊酰氯 在 五氯化磷 、 三氯氧磷 作用下， 反应 7.0h， 生成 3,6-bis[5-(pyrrolidin-1-yl)pentanamido]-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