2,6-bis(4-aminophenyl)-4-[4-(methylthio)phenyl]pyridine | 947139-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6-bis(4-aminophenyl)-4-[4-(methylthio)phenyl]pyridine
• 英文别名: 4-(p-methylthiophenyl)-2,6-bis(4-aminophenyl)pyridine；4-(p-Methylthiophenyl)-2,6-bis(4-aminophenyl) pyridine；4-[6-(4-aminophenyl)-4-(4-methylsulfanylphenyl)pyridin-2-yl]aniline
• CAS: 947139-63-1
• 化学式: C₂₄H₂₁N₃S
• 分子量: 383.517
• InChiKey: PIQSGSPDDTVXBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,6-bis(4-aminophenyl)-4-[4-(methylthio)phenyl]pyridine 反应 32.0h， 生成 N-[4-[4-(4-methylsulfanylphenyl)-6-[4-(3-pyrrolidin-1-ylpropanoylamino)phenyl]pyridin-2-yl]phenyl]-3-pyrrolidin-1-ylpropanamide
  参考文献：
  名称：

  Unraveling the relationship between structure and stabilization of triarylpyridines as G-quadruplex binding ligands

  摘要：

  我们合成了一系列新型 2,4,6-三芳基吡啶，并通过福斯特共振能量转移 (FRET) 熔化和荧光嵌入剂置换 (FID) 测定法测量了它们与分子内 G-四链体的相互作用。其中一些化合物表现出与其他基准 G4-DNA 配体相当的 G4-DNA 稳定性，具有相当出色的 G4-DNA 与双链体选择性以及对 HeLa 细胞的显着细胞毒性。 4-芳基取代基的性质以及侧链长度决定了化合物的 G4-DNA 稳定能力。此外，我们证明化合物在 K+ 和 Na+ 条件下稳定相同 G4-DNA 序列的能力之间存在很强的相关性，而化合物在 K+ 或 Na+ 条件下稳定不同 G4-DNA 序列的能力之间也存在很强的相关性。 Na+缓冲液。

  DOI：

  10.1039/c1ob05560g
• 作为产物：
  描述：

  对硝基苯乙酮 在 palladium 10% on activated carbon 、 ammonium acetate 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2,6-bis(4-aminophenyl)-4-[4-(methylthio)phenyl]pyridine
  参考文献：
  名称：

  Ionic liquid catalyzed synthesis and characterization of heterocyclic and optically active poly (amide-imide)s incorporating l-amino acids

  摘要：

  N,N'-Pyromelliticdiimido-di-l-alanine (1), N,N'-Pyromelliticdiimido-di-l-phenylalanine (2), and N,N'-Pyromelliticdiimido-di-l-leucine (3) were prepared from the reaction of Pyromellitic dianhydride with corresponding l-amino acids in a mixture of glacial acetic acid and pyridine solution (3/2 ratio) under refluxing conditions. A series of poly (amide-imide)s containing l-amino acids were prepared from the synthesized dicarboxylic acids with two synthetic aromatic diamines in an ionic liquid (IL) as a green, safe and eco-friendly medium and also reactions catalysis agent. Evaluation of data shows that IL is the better polyamidation medium than the reported method and the catalysis stand on the higher inherent viscosities of the obtained PAIs and the rate of polymerizations beyond the greener reaction conditions and deletion of some essential reagents in conventional manners. Characterization were performs by means of IR, MS and (1)H NMR spectroscopy, elemental analysis, specific rotation, thermogravimetric analysis and differential scanning calorimetric techniques. Molecular weights of the obtained polymers were evaluated viscometrically, and the measured inherent viscosities were in the range 0.43-0.85 dL/g. These polymers were readily soluble in many organic solvents. These polymers still kept good thermal stability with glass transition temperatures in the range of 94-154A degrees C, and the decomposition temperature under the nitrogen atmosphere for 10% weight-loss temperatures in excess of 308A degrees C.

  DOI：

  10.1007/s00726-010-0667-3

文献信息

• Triarylpyridine Compounds and Chloroquine Act in Concert to Trigger Lysosomal Membrane Permeabilization and Cell Death in Cancer Cells
  作者：Jennifer Beauvarlet、Rabindra Nath Das、Karla Alvarez-Valadez、Isabelle Martins、Alexandra Muller、Elodie Darbo、Elodie Richard、Pierre Soubeyran、Guido Kroemer、Jean Guillon、Jean-Louis Mergny、Mojgan Djavaheri-Mergny

  DOI：10.3390/cancers12061621

  日期：——

  Lysosomes play a key role in regulating cell death in response to cancer therapies, yet little is known on the possible role of lysosomes in the therapeutic efficacy of G-quadruplex DNA ligands (G4L) in cancer cells. Here, we investigate the relationship between the modulation of lysosomal membrane damage and the degree to which cancer cells respond to the cytotoxic effects of G-quadruplex ligands belonging to the triarylpyridine family. Our results reveal that the lead compound of this family, 20A promotes the enlargement of the lysosome compartment as well as the induction of lysosome-relevant mRNAs. Interestingly, the combination of 20A and chloroquine (an inhibitor of lysosomal functions) led to a significant induction of lysosomal membrane permeabilization coupled to massive cell death. Similar effects were observed when chloroquine was added to three new triarylpyridine derivatives. Our findings thus uncover the lysosomal effects of triarylpyridines compounds and delineate a rationale for combining these compounds with chloroquine to increase their anticancer effects.

  溶酶体在调节细胞对癌症治疗的死亡起着关键作用，然而对溶酶体在G-四链体DNA连接物（G4L）对癌细胞的治疗效果中可能发挥的作用知之甚少。在这里，我们研究了溶酶体膜损伤的调节与癌细胞对属于三芳基吡啶家族的G-四链体配体的细胞毒效应之间的关系。我们的结果显示，该家族的主要化合物20A促进了溶酶体区的扩大以及溶酶体相关mRNA的诱导。有趣的是，20A与氯喹（一种溶酶体功能抑制剂）的组合导致了溶酶体膜通透性的显著诱导，伴随着大规模的细胞死亡。当氯喹添加到三种新的三芳基吡啶衍生物中时，也观察到了类似的效应。因此，我们的发现揭示了三芳基吡啶化合物的溶酶体效应，并勾勒出了将这些化合物与氯喹结合以增强其抗癌效果的合理性。
• [EN] TRIARYLPYRIDINE COMPOUNDS AND USE THEREOF FOR TREATING CANCER<br/>[FR] COMPOSÉS DE TRIARYLPYRIDINE ET LEUR UTILISATION DANS LE CADRE DU TRAITEMENT DU CANCER
  申请人：INST NAT SANTE RECH MED

  公开号：WO2021239976A1

  公开（公告）日：2021-12-02

  The invention relates to new bis-triazole 2,4,6-triarylpyridines compounds and their use in the field of oncology, in particular in the prevention and/or treatment of cancer disease. The inventors have observed that the new bis-triazole 2,4,6-triarylpyridines were able to induce cancer cells death either as a standalone or, synergistically, in combination with a lysosomotropic agent, such as chloroquine. The compounds were active against a variety of cancer cells such as HeLa (cervical cancer cell), A549 (lung carcinoma), and PDX-2 or PDX-3 (lung adenocarcinoma). The invention also relates to compositions and methods for prevention and/or treatment of cancer diseases using the new bis-triazole 2,4,6-triarylpyridines compounds.

  该发明涉及新的双三唑基2,4,6-三芳基吡啶化合物及其在肿瘤学领域的应用，特别是在预防和/或治疗癌症疾病方面。发明人发现，新的双三唑基2,4,6-三芳基吡啶能够单独或与溶酶体靶向药物（如氯喹）联合，协同诱导癌细胞死亡。这些化合物对多种癌细胞具有活性，如HeLa（宫颈癌细胞）、A549（肺癌）和PDX-2或PDX-3（肺腺癌）。该发明还涉及使用新的双三唑基2,4,6-三芳基吡啶化合物预防和/或治疗癌症疾病的组合物和方法。
• Ionic liquid catalyzed synthesis and characterization of heterocyclic and optically active poly (amide-imide)s incorporating l-amino acids
  作者：Saeed Zahmatkesh

  DOI：10.1007/s00726-010-0667-3

  日期：2011.2

  N,N'-Pyromelliticdiimido-di-l-alanine (1), N,N'-Pyromelliticdiimido-di-l-phenylalanine (2), and N,N'-Pyromelliticdiimido-di-l-leucine (3) were prepared from the reaction of Pyromellitic dianhydride with corresponding l-amino acids in a mixture of glacial acetic acid and pyridine solution (3/2 ratio) under refluxing conditions. A series of poly (amide-imide)s containing l-amino acids were prepared from the synthesized dicarboxylic acids with two synthetic aromatic diamines in an ionic liquid (IL) as a green, safe and eco-friendly medium and also reactions catalysis agent. Evaluation of data shows that IL is the better polyamidation medium than the reported method and the catalysis stand on the higher inherent viscosities of the obtained PAIs and the rate of polymerizations beyond the greener reaction conditions and deletion of some essential reagents in conventional manners. Characterization were performs by means of IR, MS and (1)H NMR spectroscopy, elemental analysis, specific rotation, thermogravimetric analysis and differential scanning calorimetric techniques. Molecular weights of the obtained polymers were evaluated viscometrically, and the measured inherent viscosities were in the range 0.43-0.85 dL/g. These polymers were readily soluble in many organic solvents. These polymers still kept good thermal stability with glass transition temperatures in the range of 94-154A degrees C, and the decomposition temperature under the nitrogen atmosphere for 10% weight-loss temperatures in excess of 308A degrees C.
• Unraveling the relationship between structure and stabilization of triarylpyridines as G-quadruplex binding ligands
  作者：N. M. Smith、Gaëlle Labrunie、Ben Corry、Phong Lan Thao Tran、Marck Norret、Mojgan Djavaheri-Mergny、Colin L. Raston、Jean-Louis Mergny

  DOI：10.1039/c1ob05560g

  日期：——

  A series of novel 2,4,6-triarylpyridines have been synthesized and their interactions with intramolecular G-quadruplexes have been measured by Förster Resonance Energy Transfer (FRET) melting and Fluorescent Intercalator Displacement (FID) assays. A few of these compounds exhibit stabilization of G4-DNA that is comparable to other benchmark G4-DNA ligands with fair to excellent G4-DNA vs. duplex selectivity and significant cytotoxicity towards HeLa cells. The nature of the 4-aryl substituents along with side chain length governs the G4-DNA stabilization ability of the compounds. In addition, we demonstrate that there is a strong correlation between the ability of the compounds to stabilize the same G4-DNA sequence in K+ and Na+ conditions and a strong correlation between the ability of the compounds to stabilize different G4-DNA sequences in K+ or Na+ buffer.

  我们合成了一系列新型 2,4,6-三芳基吡啶，并通过福斯特共振能量转移 (FRET) 熔化和荧光嵌入剂置换 (FID) 测定法测量了它们与分子内 G-四链体的相互作用。其中一些化合物表现出与其他基准 G4-DNA 配体相当的 G4-DNA 稳定性，具有相当出色的 G4-DNA 与双链体选择性以及对 HeLa 细胞的显着细胞毒性。 4-芳基取代基的性质以及侧链长度决定了化合物的 G4-DNA 稳定能力。此外，我们证明化合物在 K+ 和 Na+ 条件下稳定相同 G4-DNA 序列的能力之间存在很强的相关性，而化合物在 K+ 或 Na+ 条件下稳定不同 G4-DNA 序列的能力之间也存在很强的相关性。 Na+缓冲液。