1-(4-{4-[4-(bromomethyl)phenyl]butyl}benzyl)-4-pyrrolidinopyridinium bromide | 1365672-08-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-{4-[4-(bromomethyl)phenyl]butyl}benzyl)-4-pyrrolidinopyridinium bromide
• 英文别名: 1-[[4-[4-[4-(Bromomethyl)phenyl]butyl]phenyl]methyl]-4-pyrrolidin-1-ylpyridin-1-ium;bromide
• CAS: 1365672-08-7
• 化学式: Br*C₂₇H₃₂BrN₂
• 分子量: 544.372
• InChiKey: DUTWNAMGIQAHGT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  7.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-{4-[4-(bromomethyl)phenyl]butyl}benzyl)-4-pyrrolidinopyridinium bromide 在 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-[4-(4-{4-[(3-hydroxyphenylamino)methyl]phenyl}-butyl)benzyl]-4-(pyrrolidin-1-yl)pyridinium bromide
  参考文献：
  名称：

  与吡啶鎓盐相关的新型 3-氨基苯酚异构体的 1H,13C NMR 研究

  摘要：

  20 种新的非对称化合物的 1H 和 13C NMR 光谱数据通过 1D 和 2D NMR 实验（DEPT、HSQC 和 HMBC）的组合指定。这些化合物含有 4-(N,N-二甲氨基)-或 4-(吡咯烷-1-基)吡啶鎓部分和 3-硝基-、3-氨基-或 3-羟基苯环，由对二甲苯连接， 4,4'-二甲基联苯、1,2-双(对甲苯基)乙烷或1,4-双(对甲苯基)丁烷。版权所有 © 2013 John Wiley & Sons, Ltd.

  DOI：

  10.1002/mrc.4025
• 作为产物：
  描述：

  1,4-二苯基-1,3丁二烯 在 磷酸 、 palladium on activated charcoal 、 氢溴酸 、 溶剂黄146 作用下， 以 丁酮 为溶剂， 反应 3.0h， 生成 1-(4-{4-[4-(bromomethyl)phenyl]butyl}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

• Antiproliferative Activity, Cell Cycle, and Apoptosis Studies of a Series of 6-Substituted 9<i>H</i>-Purin-9-yl-pyridinium Derivatives on a Human Cervical Carcinoma Cell Line
  作者：Belén Rubio-Ruiz、Javier Ramos-Torrecillas、Fermín Capitán-Cañadas、Rosario Sánchez-Martín、Miguel Ángel Gallo、Antonio Espinosa、Concepción Ruiz、Ana Conejo-García、Antonio Entrena

  DOI：10.1002/cmdc.201300171

  日期：2013.8

  Better by benzylthio: A series of 6‐substituted 9H‐purin‐9‐yl‐pyridinium derivatives was synthesized and evaluated for their antitumor activity. Compounds included in this study elicit variations in cell‐cycle progression and an increase of apoptotic cells in a caspase‐3‐dependent process.

  苄硫基更好：合成了一系列6-取代的9 H-嘌呤-9-基-吡啶鎓衍生物，并评估了其抗肿瘤活性。这项研究中包含的化合物在caspase-3依赖性过程中引起细胞周期进程的变化和凋亡细胞的增加。
• New non-symmetrical choline kinase inhibitors
  作者：Santiago Schiaffino-Ortega、Luisa Carlota López-Cara、Pablo Ríos-Marco、Maria Paz Carrasco-Jimenez、Miguel A. Gallo、Antonio Espinosa、Carmen Marco、Antonio Entrena

  DOI：10.1016/j.bmc.2013.09.003

  日期：2013.11

  Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. Choline kinase (ChoK) is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine (PC), the major phospholipid in eukaryotic cell membranes. In the present paper, a new family of non-symmetrical monocationic compounds is developed including a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. The most promising compounds in these series as ChoK inhibitors are 3f and 4f, while compounds 3c, 3d and 4c are the better antiproliferative agents. The analysis of the biological data observed in the described series of compounds mays represents a platform for the design of more active molecules. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery of a New Binding Site on Human Choline Kinase α1: Design, Synthesis, Crystallographic Studies, and Biological Evaluation of Asymmetrical Bispyridinium Derivatives
  作者：Belén Rubio-Ruiz、Ainoa Figuerola-Conchas、Javier Ramos-Torrecillas、Fermín Capitán-Cañadas、Pablo Ríos-Marco、M Paz Carrasco、Miguel Ángel Gallo、Antonio Espinosa、Carmen Marco、Concepción Ruiz、Antonio Entrena、Ramon Hurtado-Guerrero、Ana Conejo-García

  DOI：10.1021/jm401665x

  日期：2014.1.23

  Human choline kinase alpha (CK alpha) is a validated drug target for the treatment of cancer. In recent years, a large number of CK inhibitors have been synthesized, and one of them is currently being evaluated in Phase I clinical trials as a treatment for solid tumors. Here we have evaluated a new series of asymmetrical biscationic CK inhibitors by means of enzymatic, crystallographic, and antitumor studies. We demonstrate that one of these structures adopts a completely new binding mode not observed before inducing the aperture of an adjacent binding site. This compound shows antiproliferative and apoptotic effects on cancer cells through activation of caspase-3. Therefore, this study not only provides fruitful insights into the design of more efficient compounds that may target different regions in CK alpha 1 but also explains how these compounds induce apoptosis in cancer cells.
• ¹ H, ¹³ C NMR studies of new 3-aminophenol isomers linked to pyridinium salts
  作者：Santiago Schiaffino-Ortega、Antonio Espinosa、Miguel A. Gallo、L. Carlota López-Cara、Antonio Entrena

  DOI：10.1002/mrc.4025

  日期：2014.1

  1H and 13C NMR spectroscopic data of 20 new non‐symmetrical compounds were assigned by a combination of 1D and 2D NMR experiments (DEPT, HSQC, and HMBC). These compounds contain a 4‐(N,N‐dimethylamino)‐ or 4‐(pyrrolidin‐1‐yl)pyridinium moiety and a 3‐nitro‐, 3‐amino‐, or 3‐hydroxyphenyl ring, linked by p‐xylene, 4,4′‐dimethylbiphenyl, 1,2‐bis(p‐tolyl)ethane, or 1,4‐bis(p‐tolyl)butane. Copyright © 2013

  20 种新的非对称化合物的 1H 和 13C NMR 光谱数据通过 1D 和 2D NMR 实验（DEPT、HSQC 和 HMBC）的组合指定。这些化合物含有 4-(N,N-二甲氨基)-或 4-(吡咯烷-1-基)吡啶鎓部分和 3-硝基-、3-氨基-或 3-羟基苯环，由对二甲苯连接， 4,4'-二甲基联苯、1,2-双(对甲苯基)乙烷或1,4-双(对甲苯基)丁烷。版权所有 © 2013 John Wiley & Sons, Ltd.
• 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.