6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline | 387371-66-6

• 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: 6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline
• 英文别名: 6-pyridyl-5,6-dihydrobenzo[4-5]imidazo[1,2-c]quinazoline；6-Pyridin-2-yl-6,12-dihydrobenzimidazolo[1,2-c]quinazoline；6-pyridin-2-yl-5,6-dihydrobenzimidazolo[1,2-c]quinazoline
• CAS: 387371-66-6
• 化学式: C₁₉H₁₄N₄
• 分子量: 298.347
• InChiKey: ZMZZAQWHHFSQPH-UHFFFAOYSA-N

物化性质

• 沸点：
  576.9±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline 在 potassium permanganate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以97%的产率得到6-(2-pyridyl)benzo[4,5]imidazo[1,2-c]quinazoline
  参考文献：
  名称：

  Synthesis, characterization, crystal structure, and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative

  摘要：

  The reaction of cis-[RuCl2(dmso)(4)] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c] quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L-1)(2)] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL1). Treatment of RuCl3 center dot 3H(2)O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl2(L-2)(2)] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c] quinazoline (L-2). Complex 2 was also obtained from the reaction of RuCl3 center dot 3H(2)O with L-2 in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K-b and the linear Stern-Volmer quenching constant K-SV.

  DOI：

  10.1080/00958972.2012.667807
• 作为产物：
  描述：

  吡啶-2-甲醛 、 2-(2-氨基苯基)苯并咪唑 以 乙醇 为溶剂， 反应 5.0h， 以60%的产率得到6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline
  参考文献：
  名称：

  6-p-Dimethylaminophenyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline 的合成、表征和生物活性研究：标题化合物的晶体结构和相关衍生物的比较研究

  摘要：

  邻氨基苯基苯并咪唑与对二甲氨基苯甲醛反应生成 6-对二甲氨基苯基-5,6-二氢苯并咪唑并[1,2-c]喹唑啉，通过元素分析、IR、UV-Vis、1H NMR、13C NMR、质量光谱研究和 X 射线晶体结构分析。对该化合物抗菌活性的研究表明，它对真菌酵母菌具有活性，但对枯草芽孢杆菌无效。该化合物在空间群 P21/n 中结晶，晶胞参数 a = 10.652(2) Å, b = 11.002(2) Å, c = 15.753(2) Å, β = 109.29(2)°，结构为细化到 0.0479 的 R 因子。喹唑啉部分中的氢嘧啶环呈斜船构象。与苯环相连的二甲氨基与其共轭。结构通过分子间 C-H-N 相互作用稳定。

  DOI：

  10.1007/s10870-011-0243-z

文献信息

• Benzimidazoles for the treatment of cancer
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2698367A1

  公开（公告）日：2014-02-19

  The present invention relates to novel substituted benzimidazoles and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these substituted benzimidazoles together with pharmaceutically acceptable carrier, excipient and/or diluents. Said novel substituted benzimidazoles binding to the prenyl binding pocket of PDEδ have been identified as useful for the prophylaxis and treatment of cancer by the inhibition of the binding of PDEδ to K-Ras and of oncogenic Ras signalling in cells by altering its localization leading to cell death or inhibition of proliferation.

  本发明涉及新型取代苯并咪唑和立体异构体形式，以及这些化合物的前药、溶剂化合物、水合物和/或药学上可接受的盐，以及含有至少一种这些取代苯并咪唑的药物组合物，与药学上可接受的载体、赋形剂和/或稀释剂一起。已确定这些新型取代苯并咪唑结合到PDEδ的藤黄素结合口袋，通过抑制PDEδ与K-Ras的结合以及通过改变其定位导致细胞死亡或抑制增殖，从而对癌症的预防和治疗有用。
• [EN] BENZIMIDAZOLES FOR THE TREATMENT OF CANCER<br/>[FR] BENZIMIDAZOLES POUR LE TRAITEMENT D'UN CANCER
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2014027053A1

  公开（公告）日：2014-02-20

  The present invention relates to novel substituted benzimidazoles and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these substituted benzimidazoles together with pharmaceutically acceptable carrier, excipient and/or diluents. Said novel substituted benzimidazoles binding to the prenyl binding pocket of PDEδ have been identified as useful for the prophylaxis and treatment of cancer by the inhibition of the binding of PDEδ to K-Ras and of oncogenic Ras signalling in cells by altering its localization leading to cell death or inhibition of proliferation.

  本发明涉及新型取代苯并咪唑和立体异构体形式，以及这些化合物的前药、溶剂化合物、水合物和/或药学上可接受的盐，以及含有至少一种这些取代苯并咪唑的药物组合物，与药学上可接受的载体、赋形剂和/或稀释剂一起。已经确定这些新型取代苯并咪唑结合到PDEδ的藤黄素结合口袋，对于通过抑制PDEδ与K-Ras的结合以及通过改变其定位导致细胞死亡或抑制增殖而对癌症的预防和治疗是有用的。
• Synthesis, Characterization and Biological Activity Studies on 6-p-Dimethylaminophenyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline: Crystal Structure of the Title Compound and Comparative Study with Related Derivatives
  作者：S. G. Bubbly、S. B. Gudennavar、N. M. Nanje Gowda、Rita Bhattacharjee、V. Gayathri、S. Natarajan

  DOI：10.1007/s10870-011-0243-z

  日期：2012.4

  with it. The structure was stabilized by intermolecular C–H–N interactions. A few of the related quinazolines (6-p-hydroxyphenyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline; 6-phenyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline; 6-pyridyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline; 6-furyl-5,6-dihydrobenzoimidazo[1,2-c]quinazoline) were also examined for their biological activity, in addition to their characterization

  邻氨基苯基苯并咪唑与对二甲氨基苯甲醛反应生成 6-对二甲氨基苯基-5,6-二氢苯并咪唑并[1,2-c]喹唑啉，通过元素分析、IR、UV-Vis、1H NMR、13C NMR、质量光谱研究和 X 射线晶体结构分析。对该化合物抗菌活性的研究表明，它对真菌酵母菌具有活性，但对枯草芽孢杆菌无效。该化合物在空间群 P21/n 中结晶，晶胞参数 a = 10.652(2) Å, b = 11.002(2) Å, c = 15.753(2) Å, β = 109.29(2)°，结构为细化到 0.0479 的 R 因子。喹唑啉部分中的氢嘧啶环呈斜船构象。与苯环相连的二甲氨基与其共轭。结构通过分子间 C-H-N 相互作用稳定。
• Synthesis, characterization, crystal structure, and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative
  作者：H. Paul、T. Mukherjee、M.G.B. Drew、P. Chattopadhyay

  DOI：10.1080/00958972.2012.667807

  日期：2012.4.20

  The reaction of cis-[RuCl2(dmso)(4)] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c] quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L-1)(2)] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL1). Treatment of RuCl3 center dot 3H(2)O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl2(L-2)(2)] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c] quinazoline (L-2). Complex 2 was also obtained from the reaction of RuCl3 center dot 3H(2)O with L-2 in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K-b and the linear Stern-Volmer quenching constant K-SV.