2-[({1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazol-5-yl}oxy)methyl]quinoline | 1382488-18-7

• 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: 2-[({1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazol-5-yl}oxy)methyl]quinoline
• 英文别名: 2-[[1-[(2-Chlorophenyl)methyl]-2-[1-[4-(2-methylpropyl)phenyl]ethyl]benzimidazol-5-yl]oxymethyl]quinoline
• CAS: 1382488-18-7
• 化学式: C₃₆H₃₄ClN₃O
• 分子量: 560.138
• InChiKey: UGASTDYELDRSCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(2-氯苄基)-4-甲氧基-2-硝基苯胺 在 tin(II) chloride dihdyrate 、 氢溴酸 、 四丁基碘化铵 、 caesium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 2-[({1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazol-5-yl}oxy)methyl]quinoline
  参考文献：
  名称：

  Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein (FLAP)

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand-and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 mu M) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 mu M in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.048

文献信息

• Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein (FLAP)
  作者：Erden Banoglu、Burcu Çalışkan、Susann Luderer、Gökçen Eren、Yagmur Özkan、Wolfram Altenhofen、Christina Weinigel、Dagmar Barz、Jana Gerstmeier、Carlo Pergola、Oliver Werz

  DOI：10.1016/j.bmc.2012.04.048

  日期：2012.6

  Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand-and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 mu M) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 mu M in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents. (C) 2012 Elsevier Ltd. All rights reserved.