3,6-diazido-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine | 875924-02-0

• 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-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine
• 英文别名: N-[4-[(3,6-diazidoacridin-9-yl)amino]phenyl]-3-pyrrolidin-1-ylpropanamide
• CAS: 875924-02-0
• 化学式: C₂₆H₂₄N₁₀O
• 分子量: 492.543
• InChiKey: OCFKEVVNKGMDCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3,6-diazido-9-{4'-[3''-(pyrrolidin-1-yl)propanamido]anilino}acridine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 150.0 ℃ 、137.9 kPa 条件下， 反应 1.08h， 生成 3,6-bis(5-chloropentanamido)-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
• 作为产物：
  描述：

  3,6-二氨基-9-吖啶酮 在 盐酸 、 氯化亚砜 、 sodium azide 、 硫酸 、 sodium nitrite 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 1.0h， 生成 3,6-diazido-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

文献信息

• 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
  作者：Michael J. B. Moore、Christoph M. Schultes、Javier Cuesta、Francisco Cuenca、Mekala Gunaratnam、Farial A. Tanious、W. David Wilson、Stephen Neidle

  DOI：10.1021/jm050555a

  日期：2006.1.1

  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.