4-chloro-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide | 1159206-13-9

• 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-chloro-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide
• 英文别名: 4-chloro-N²,N⁶-di(quinolin-3-yl)pyridine-2,6-dicarboxamide；4-chloro-N²,N⁶-bis(3-quinolyl)pyridine-2,6-dicarboxamide；N2,N6-di(quinolin-3-yl)-4-chloro-pyridine-2,6-dicarboxamide
• CAS: 1159206-13-9
• 化学式: C₂₅H₁₆ClN₅O₂
• 分子量: 453.887
• InChiKey: UQINPBYXMKXHSE-UHFFFAOYSA-N

物化性质

• 沸点：
  596.2±50.0 °C(Predicted)
• 密度：
  1.478±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.87
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-chloro-N2,N6-di(quinolin-3-yl)pyridine-2,6-dicarboxamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.5h， 生成
  参考文献：
  名称：

  BrdU immuno-tagged G-quadruplex ligands: a new ligand-guided immunofluorescence approach for tracking G-quadruplexes in cells

  摘要：

  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。

  DOI：

  10.1093/nar/gkab1166
• 作为产物：
  描述：

  4-氧代-1,4-二氢-2,6-吡啶二甲酸 在 五氯化磷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-chloro-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

• Binding properties of mono- and dimeric pyridine dicarboxamide ligands to human telomeric higher-order G-quadruplex structures
  作者：C. Saintomé、P. Alberti、N. Guinot、P. Lejault、J. Chatain、P. Mailliet、J.-F. Riou、A. Bugaut

  DOI：10.1039/c7cc07048a

  日期：——

  A new dimeric ligand binds telomeric contiguous G4s, displacing the single-stranded DNA binding RPA more efficiently than its monomeric counterpart.

  一个新的二聚配体结合端粒连续的G4，比其单体对应物更有效地取代单链DNA结合RPA。
• Topology-Selective, Fluorescent “Light-Up” Probes for G-Quadruplex DNA Based on Photoinduced Electron Transfer
  作者：Xiao Xie、Oksana Reznichenko、Ludovic Chaput、Pascal Martin、Marie-Paule Teulade-Fichou、Anton Granzhan

  DOI：10.1002/chem.201801701

  日期：2018.8.27

  Six novel probes were prepared by covalent attachment of a G4‐DNA ligand (bis(quinolinium) pyridodicarboxamide; PDC) to various coumarin or pyrene fluorophores. In the absence of DNA, the fluorescence of all probes is quenched due to intramolecular photoinduced electron transfer (PET), as evidenced by photophysical and electrochemical studies, molecular modeling, and DFT calculations. All probes demonstrate

  通过将G4-DNA配体（双（喹啉鎓）吡啶二甲酰胺; PDC）共价连接到各种香豆素或pyr荧光基团上制备了六种新颖的探针。在不存在DNA的情况下，由于分子内的光诱导电子转移（PET），所有探针的荧光都被淬灭，这一点已通过光物理和电化学研究，分子建模和DFT计算得到了证明。所有探针均显示出不同的G4-DNA底物具有相似的高热稳定性，这些底物属于不同的折叠拓扑结构，这是通过荧光熔解实验评估得出的；但是，它们的荧光响应在探针和G4-DNA靶标的结构上是高度异质的。因此，在存在G4-DNA的情况下，含有7-二乙基氨基香豆素荧光团的探针显示出显着的荧光增强，对反平行G4结构以及由人端粒序列变体形成的杂合G4结构观察到最强的“亮起”响应（20到180倍），并且能够构象改变为反平行同种型。这些结果揭示了荧光团的接头和电子性质对通过PET操作的G4-DNA“发光”探针效率的影响。
• Teaching photosensitizers a new trick: red light-triggered G-quadruplex alkylation by ligand co-localization
  作者：Enrico Cadoni、Alex Manicardi、Mathieu Fossépré、Kaat Heirwegh、Mathieu Surin、Annemieke Madder

  DOI：10.1039/d0cc06030e

  日期：——

  A red-light triggered G-quadruplex photoalkylation procedure is reported, based on a bi-molecular approach involving the irradiation of a G4-binding photosensitizer in presence of a furan-containing G4-ligand.

  报道了一种基于双分子方法的红光触发的G-四链体光烷基化过程，该方法涉及在存在含有呋喃基G4配体的情况下照射G4结合光敏剂。
• Effects of a halogenated G-quadruplex ligand from the pyridine dicarboxamide series on the terminal sequence of XpYp telomere in HT1080 cells
  作者：Assitan Sidibe、Florian Hamon、Eric Largy、Dennis Gomez、Marie-Paule Teulade-Fichou、Chantal Trentesaux、Jean-François Riou

  DOI：10.1016/j.biochi.2012.07.003

  日期：2012.12

  Non-canonical four-stranded structures called G-quadruplexes can form among telomere repeats during its replication. Small molecule ligands able to interact and to stabilize G-quadruplexes were shown to disrupt the binding of essential telomeric components, such as POT] and to trigger a telomeric dysfunction associated with a delayed growth arrest in tumor cells. We describe here the chemical synthesis and the G-quadruplex binding properties of three halogenated analogs of the 360A ligand that belongs to the 2,6 pyridine dicarboxamide series. 360A is now commonly used as a benchmark both for biophysical and cellular assays as this compound was shown to display a potent affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA and to induce delayed growth inhibition in HT1080 tumor cell line. Two biophysical assays indicate that, in most cases, the presence of the halogen atom seems to slightly improve the interaction with the telomeric quadruplex. For stability reasons, the bromo derivative (360A-Br) was selected for the cellular assays. Since POT1 participates to the fine tuning of the C-strand end resection during telomere replication, we investigated the effect of 360A-Br to alter the terminal nucleotide composition of XpYp telomere in HT1080 cells using C-STELA. HT1080 cells treated for up to 24 days with 360A-Br presented some minor but significant variations of C-strand terminal nucleotide composition, also observed with a partial siRNA depletion of POT1. The relevance of these minor modifications of the telomeric C-strand resection induced by 360A-Br in HT1080 cells are discussed. (C) 2012 Elsevier Masson SAS. All rights reserved.
• 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.