1-{4-[(6-amino-9H-purin-9-yl)methyl]benzyl}-4-pyrrolidinopyridinium bromide | 1365671-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1-{4-[(6-amino-9H-purin-9-yl)methyl]benzyl}-4-pyrrolidinopyridinium bromide
• 英文别名: 9-[[4-[(4-Pyrrolidin-1-ylpyridin-1-ium-1-yl)methyl]phenyl]methyl]purin-6-amine;bromide
• CAS: 1365671-49-3
• 化学式: Br*C₂₂H₂₄N₇
• 分子量: 466.383
• InChiKey: HGDUFSDWVKFEHM-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,4-二(溴甲基)苯 、 4-吡咯烷基吡啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 3.5h， 生成 1-{4-[(6-amino-9H-purin-9-yl)methyl]benzyl}-4-pyrrolidinopyridinium bromide
  参考文献：
  名称：

  Design, synthesis, theoretical calculations and biological evaluation of new non-symmetrical choline kinase inhibitors

  摘要：

  Inhibition of Choline Kinase (ChoK) has been reported as a therapeutical target in the treatment of some kinds of tumor. In this paper, the design and synthesis of new non-symmetrical monocationic ChoK inhibitors is described, bearing a cationic head and an adenine moiety connected by linkers of different lengths. Docking studies indicate that the cationic head of these compounds could be inserted into the choline binding site of the enzyme, while the adenine moiety could be stabilized into the ATP binding site. Docking studies also support the difference of activity of the synthesized compounds, which depends on both the substituent at position 4 of the cationic head and the linker length, being dimethylamine and 1,4-diphenylbutane respectively, the most appropriate ones. Compounds 14 (IC50 = 10.70 +/- 0.40 mu M) and 17 (IC50 = 6.21 +/- 0.97 mu M) are the most potent ChoK inhibitors and suitable for further modification with a view to obtain more potent antitumor compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.050

文献信息

• Design, synthesis, theoretical calculations and biological evaluation of new non-symmetrical choline kinase inhibitors
  作者：Belén Rubio-Ruíz、Ana Conejo-García、Pablo Ríos-Marco、María Paz Carrasco-Jiménez、Josefa Segovia、Carmen Marco、Miguel A. Gallo、Antonio Espinosa、Antonio Entrena

  DOI：10.1016/j.ejmech.2012.01.050

  日期：2012.4

  Inhibition of Choline Kinase (ChoK) has been reported as a therapeutical target in the treatment of some kinds of tumor. In this paper, the design and synthesis of new non-symmetrical monocationic ChoK inhibitors is described, bearing a cationic head and an adenine moiety connected by linkers of different lengths. Docking studies indicate that the cationic head of these compounds could be inserted into the choline binding site of the enzyme, while the adenine moiety could be stabilized into the ATP binding site. Docking studies also support the difference of activity of the synthesized compounds, which depends on both the substituent at position 4 of the cationic head and the linker length, being dimethylamine and 1,4-diphenylbutane respectively, the most appropriate ones. Compounds 14 (IC50 = 10.70 +/- 0.40 mu M) and 17 (IC50 = 6.21 +/- 0.97 mu M) are the most potent ChoK inhibitors and suitable for further modification with a view to obtain more potent antitumor compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.