N,N'-di(quinolin-3-yl)-1,8-naphthyridine-2,7-dicarboxamide | 1351522-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N,N'-di(quinolin-3-yl)-1,8-naphthyridine-2,7-dicarboxamide
• 英文别名: 2-N,7-N-di(quinolin-3-yl)-1,8-naphthyridine-2,7-dicarboxamide
• CAS: 1351522-51-4
• 化学式: C₂₈H₁₈N₆O₂
• 分子量: 470.49
• InChiKey: RJPHQSOHPHWVMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-di(quinolin-3-yl)-1,8-naphthyridine-2,7-dicarboxamide 、 三氟甲烷磺酸甲酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以55%的产率得到3,3'-[1,8-naphthyridinediyl-2,7-bis(carbonylimino)]bis(1-methylquinolinium) triflate
  参考文献：
  名称：

  Selective G-quadruplex DNA Stabilizing Agents Based on Bisquinolinium and Bispyridinium Derivatives of 1,8-Naphthyridine

  摘要：

  Various biologically relevant G-quadruplex DNA structures offer a platform for therapeutic intervention for altering the gene expression or by halting the function of proteins associated with telomeres. One of the prominent strategies to explore the therapeutic potential of quadruplex DNA structures is by stabilizing them with small molecule ligands. Here we report the synthesis of bisquinolinium and bispyridinium derivatives of 1,8-naphthyridine and their interaction with human telomeric DNA and promoter G-quadruplex forming DNAs. The interactions of ligands with quadruplex forming DNAs were studied by various biophysical, biochemical, and computational methods. Results indicated that bisquinolinium ligands bind tightly and selectively to quadruplex DNAs at low ligand concentration (similar to 0.2-0.4 mu M). Furthermore, thermal melting studies revealed that ligands imparted higher stabilization for quadruplex DNA (an increase in the T-m of up to 21 degrees C for human telomeric G-quadruplex DNA and >25 degrees C for promoter G-quadruplex DNAs) than duplex DNA (Delta T-m < 1.6 degrees C). Molecular dynamics simulations revealed that the end-stacking binding mode was favored for ligands with low binding free energy. Taken together, the results indicate that the naphthyridine-based ligands with quinolinium and pyridinium side chains form a promising class of quadruplex DNA stabilizing agents having high selectivity for quadruplex DNA structures over duplex DNA structures.

  DOI：

  10.1021/jo201816g
• 作为产物：
  描述：

  4-氯-2,7-二甲基-1,8-二氮杂萘 在 4-二甲氨基吡啶 、 selenium(IV) oxide 、 palladium 10% on activated carbon 、 甲酸铵 、 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 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 N,N'-di(quinolin-3-yl)-1,8-naphthyridine-2,7-dicarboxamide
  参考文献：
  名称：

  Selective G-quadruplex DNA Stabilizing Agents Based on Bisquinolinium and Bispyridinium Derivatives of 1,8-Naphthyridine

  摘要：

  Various biologically relevant G-quadruplex DNA structures offer a platform for therapeutic intervention for altering the gene expression or by halting the function of proteins associated with telomeres. One of the prominent strategies to explore the therapeutic potential of quadruplex DNA structures is by stabilizing them with small molecule ligands. Here we report the synthesis of bisquinolinium and bispyridinium derivatives of 1,8-naphthyridine and their interaction with human telomeric DNA and promoter G-quadruplex forming DNAs. The interactions of ligands with quadruplex forming DNAs were studied by various biophysical, biochemical, and computational methods. Results indicated that bisquinolinium ligands bind tightly and selectively to quadruplex DNAs at low ligand concentration (similar to 0.2-0.4 mu M). Furthermore, thermal melting studies revealed that ligands imparted higher stabilization for quadruplex DNA (an increase in the T-m of up to 21 degrees C for human telomeric G-quadruplex DNA and >25 degrees C for promoter G-quadruplex DNAs) than duplex DNA (Delta T-m < 1.6 degrees C). Molecular dynamics simulations revealed that the end-stacking binding mode was favored for ligands with low binding free energy. Taken together, the results indicate that the naphthyridine-based ligands with quinolinium and pyridinium side chains form a promising class of quadruplex DNA stabilizing agents having high selectivity for quadruplex DNA structures over duplex DNA structures.

  DOI：

  10.1021/jo201816g

文献信息

• Selective G-quadruplex DNA Stabilizing Agents Based on Bisquinolinium and Bispyridinium Derivatives of 1,8-Naphthyridine
  作者：V. Dhamodharan、S. Harikrishna、C. Jagadeeswaran、K. Halder、P. I. Pradeepkumar

  DOI：10.1021/jo201816g

  日期：2012.1.6

  Various biologically relevant G-quadruplex DNA structures offer a platform for therapeutic intervention for altering the gene expression or by halting the function of proteins associated with telomeres. One of the prominent strategies to explore the therapeutic potential of quadruplex DNA structures is by stabilizing them with small molecule ligands. Here we report the synthesis of bisquinolinium and bispyridinium derivatives of 1,8-naphthyridine and their interaction with human telomeric DNA and promoter G-quadruplex forming DNAs. The interactions of ligands with quadruplex forming DNAs were studied by various biophysical, biochemical, and computational methods. Results indicated that bisquinolinium ligands bind tightly and selectively to quadruplex DNAs at low ligand concentration (similar to 0.2-0.4 mu M). Furthermore, thermal melting studies revealed that ligands imparted higher stabilization for quadruplex DNA (an increase in the T-m of up to 21 degrees C for human telomeric G-quadruplex DNA and >25 degrees C for promoter G-quadruplex DNAs) than duplex DNA (Delta T-m < 1.6 degrees C). Molecular dynamics simulations revealed that the end-stacking binding mode was favored for ligands with low binding free energy. Taken together, the results indicate that the naphthyridine-based ligands with quinolinium and pyridinium side chains form a promising class of quadruplex DNA stabilizing agents having high selectivity for quadruplex DNA structures over duplex DNA structures.