4-((4-aminobutyl)amino)-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide | 1202899-91-9

• 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: 4-((4-aminobutyl)amino)-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide
• 英文别名: 4-[(4-aminobutyl)amino]-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide
• CAS: 1202899-91-9
• 化学式: C₂₉H₂₇N₇O₂
• 分子量: 505.579
• InChiKey: HTEBUIBLTMROAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  134.92
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-苯甲酰苯甲酸 、 4-((4-aminobutyl)amino)-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以58%的产率得到4-((4-(4-benzoylbenzamido)butyl)amino)-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide
  参考文献：
  名称：

  Photo-Cross-Linking Probes for Trapping G-Quadruplex DNA

  摘要：

  AbstractWe have developed a straightforward synthetic pathway to a set of six photoactivatable G‐quadruplex ligands with a validated G4‐binding motif (the bisquinolinium pyridodicarboxamide PDC‐360A) tethered through various spacers to two different photo‐cross‐linking groups: benzophenone and an aryl azide. The high quadruplex‐versus‐duplex selectivity of the PDC core was retained in the new derivatives and resulted in selective alkylation of two well‐known G‐quadruplexes (human telomeric G4 and oncogene promoter c‐myc G4) under conditions of harsh competition. The presence of two structurally different photoactivatable functions allowed the selective alkylation of G‐quadruplex structures at specific nucleobases and irreversible G4 binding. The topology and sequence of the quadruplex matrix appear to influence strongly the alkylation profile, which differs for the telomeric and c‐myc quadruplexes. The new compounds are photoactive in cells and thus provide new tools for studying G4 biology.

  DOI：

  10.1002/anie.201307413
• 作为产物：
  描述：

  4-氯吡啶-2,6-二羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-((4-aminobutyl)amino)-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide
  参考文献：
  名称：

  反肿瘤反式NHC-Pt（II）配合物与G-四链体DNA配体的端粒靶向。

  摘要：

  G-四链体结构（G4）是有前途的抗癌目标。已经通过生物物理方法鉴定了许多靶向这些结构的小分子。在纤维素中，它们中的一些能够靶向端粒DNA和/或致癌基因启动子中涉及的某些序列，均导致癌细胞死亡。然而，它们中只有少数能够不可逆地结合至这些结构G4。在这里，我们将G4结合剂PDC（吡啶二甲酰胺）与已经鉴定出其抗肿瘤特性的N-杂环卡宾-铂络合物NHC-Pt结合在一起。所得的共轭铂络合物NHC-Pt-PDC与PDC相比，在体外可稳定地稳定G-四链体结构，亲和力受到的影响较小。此外，我们表明，新的缀合物优先且不可逆地以与NHC-Pt不同的方式与人端粒序列的四链体形式结合，从而表明通过将PDC部分堆叠到PDC上来定向电镀反应。G4结构。在纤维素中，NHC-Pt-PDC引起端粒TRF2的大量损失，这比单独使用其两个组分PDC和NHC-Pt的作用要重要得多。

  DOI：

  10.1021/acs.bioconjchem.6b00079

文献信息

• Copper-Alkyne Complexation Responsible for the Nucleolar Localization of Quadruplex Nucleic Acid Drugs Labeled by Click Reactions
  作者：Joël Lefebvre、Corinne Guetta、Florent Poyer、Florence Mahuteau-Betzer、Marie-Paule Teulade-Fichou

  DOI：10.1002/anie.201703783

  日期：2017.9.11

  in vitro and in cells. We explored the cellular localization of PhenDC3, one of the most powerful G4 ligands, by synthesizing two clickable azide and alkyne derivatives (PhenDC3‐alk, PhenDC3‐az) and labeling them in situ with the corresponding Cy5 click partners. A careful comparison of the results obtained for the copper‐based CuAAC and copper‐free SPAAC methodologies in fixed cells implicated CuI/alkyne

  G-四链体（G4）是在富含鸟嘌呤的序列中发现的非规范核酸结构。可以用充当报道分子的小分子（G4配体）作为靶标，以在体外和细胞中进行追踪。我们通过合成两个可点击的叠氮化物和炔烃衍生物（PhenDC 3 alk，PhenDC 3 az）并用相应的Cy5 click合作伙伴原位标记，探索了最强大的G4配体之一PhenDC 3的细胞定位。仔细比较固定单元中涉及铜I的铜基CuAAC和无铜SPAAC方法获得的结果/炔中间体的非特异性配体（和荧光团）定位于核仁。相比之下，SPAAC在固定细胞和活细胞中产生相似的核质标记模式。我们的发现表明，在使用CuAAC在细胞中定位药物时需要格外小心，并且表明SPAAC所提供的结果在固定细胞和活细胞之间更加一致。
• BrdU immuno-tagged G-quadruplex ligands: a new ligand-guided immunofluorescence approach for tracking G-quadruplexes in cells
  作者：Thibaut Masson、Corinne Landras Guetta、Eugénie Laigre、Anne Cucchiarini、Patricia Duchambon、Marie-Paule Teulade-Fichou、Daniela Verga

  DOI：10.1093/nar/gkab1166

  日期：2021.12.16

  G-quadruplexes (G4s) are secondary structures forming in G-rich nucleic acids. G4s are assumed to play critical roles in biology, nonetheless their detection in cells is still challenging. For tracking G4s, synthetic molecules (G4 ligands) can be used as reporters and have found wide application for this purpose through chemical functionalization with a fluorescent tag. However, this approach is limited by a low-labeling degree impeding precise visualization in specific subcellular regions. Herein, we present a new visualization strategy based on the immuno-recognition of 5-bromo-2′-deoxyuridine (5-BrdU) modified G4 ligands, functionalized prior- or post-G4-target binding by CuAAC. Remarkably, recognition of the tag by antibodies leads to the detection of the modified ligands exclusively when bound to a G4 target both in vitro, as shown by ELISA, and in cells, thereby providing a highly efficient G4-ligand Guided Immunofluorescence Staining (G4-GIS) approach. The obtained signal amplification revealed well-defined fluorescent foci located in the perinuclear space and RNase treatment revealed the preferential binding to G4-RNA. Furthermore, ligand treatment affected significantly BG4 foci formation in cells. Our work headed to the development of a new imaging approach combining the advantages of immunostaining and G4-recognition by G4 ligands leading to visualization of G4/ligands species in cells with unrivaled precision and sensitivity.

  G-四链体（G4s）是形成在富含G的核酸中的二级结构。G4s被认为在生物学中发挥着关键作用，尽管它们在细胞中的检测仍然具有挑战性。为了追踪G4s，可以使用合成分子（G4配体）作为报告者，并通过化学功能化与荧光标签进行广泛应用。然而，这种方法受到标记度低的限制，影响了在特定亚细胞区域的精确可视化。在此，我们提出了一种基于5-溴-2'-脱氧尿嘧啶（5-BrdU）修饰的G4配体的免疫识别的新的可视化策略，通过CuAAC在G4目标结合之前或之后进行功能化。值得注意的是，抗体对标签的识别仅在修饰的配体与G4靶标结合时才能在体外（如ELISA所示）和细胞中检测到，从而提供了一种高效的G4配体引导免疫荧光染色（G4-GIS）方法。所获得的信号放大显示出位于周核空间的明确定义的荧光焦点，并且RNase处理显示出对G4-RNA的优先结合。此外，配体处理显著影响了细胞中BG4焦点的形成。我们的工作旨在开发一种新的成像方法，结合免疫染色和G4配体对G4 /配体物种的识别优势，以实现细胞中G4 /配体物种的无与伦比的精确度和灵敏度可视化。

• Linking of Antitumor <i>trans</i> NHC-Pt(II) Complexes to G-Quadruplex DNA Ligand for Telomeric Targeting
  作者：Jean-François Betzer、Frédérick Nuter、Mélanie Chtchigrovsky、Florian Hamon、Guillaume Kellermann、Samar Ali、Marie-Ange Calméjane、Sylvain Roque、Joël Poupon、Thierry Cresteil、Marie-Paule Teulade-Fichou、Angela Marinetti、Sophie Bombard

  DOI：10.1021/acs.bioconjchem.6b00079

  日期：2016.6.15

  G-quadruplex structures (G4) are promising anticancerous targets. A great number of small molecules targeting these structures have already been identified through biophysical methods. In cellulo, some of them are able to target either telomeric DNA and/or some sequences involved in oncogene promotors, both resulting in cancer cell death. However, only a few of them are able to bind to these structures

  G-四链体结构（G4）是有前途的抗癌目标。已经通过生物物理方法鉴定了许多靶向这些结构的小分子。在纤维素中，它们中的一些能够靶向端粒DNA和/或致癌基因启动子中涉及的某些序列，均导致癌细胞死亡。然而，它们中只有少数能够不可逆地结合至这些结构G4。在这里，我们将G4结合剂PDC（吡啶二甲酰胺）与已经鉴定出其抗肿瘤特性的N-杂环卡宾-铂络合物NHC-Pt结合在一起。所得的共轭铂络合物NHC-Pt-PDC与PDC相比，在体外可稳定地稳定G-四链体结构，亲和力受到的影响较小。此外，我们表明，新的缀合物优先且不可逆地以与NHC-Pt不同的方式与人端粒序列的四链体形式结合，从而表明通过将PDC部分堆叠到PDC上来定向电镀反应。G4结构。在纤维素中，NHC-Pt-PDC引起端粒TRF2的大量损失，这比单独使用其两个组分PDC和NHC-Pt的作用要重要得多。
• Photo-Cross-Linking Probes for Trapping G-Quadruplex DNA
  作者：Daniela Verga、Florian Hamon、Florent Poyer、Sophie Bombard、Marie-Paule Teulade-Fichou

  DOI：10.1002/anie.201307413

  日期：2014.1.20

  AbstractWe have developed a straightforward synthetic pathway to a set of six photoactivatable G‐quadruplex ligands with a validated G4‐binding motif (the bisquinolinium pyridodicarboxamide PDC‐360A) tethered through various spacers to two different photo‐cross‐linking groups: benzophenone and an aryl azide. The high quadruplex‐versus‐duplex selectivity of the PDC core was retained in the new derivatives and resulted in selective alkylation of two well‐known G‐quadruplexes (human telomeric G4 and oncogene promoter c‐myc G4) under conditions of harsh competition. The presence of two structurally different photoactivatable functions allowed the selective alkylation of G‐quadruplex structures at specific nucleobases and irreversible G4 binding. The topology and sequence of the quadruplex matrix appear to influence strongly the alkylation profile, which differs for the telomeric and c‐myc quadruplexes. The new compounds are photoactive in cells and thus provide new tools for studying G4 biology.