2-<1-(4-isobutylphenyl)ethyl>-1H-benzimidazole | 129226-09-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-<1-(4-isobutylphenyl)ethyl>-1H-benzimidazole
• 英文别名: 2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazole；1H-Benzimidazole, 2-[1-[4-(2-methylpropyl)phenyl]ethyl]-；2-[1-[4-(2-methylpropyl)phenyl]ethyl]-1H-benzimidazole
• CAS: 129226-09-1
• 化学式: C₁₉H₂₂N₂
• 分子量: 278.397
• InChiKey: SOGGLHQFUVHVFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-<1-(4-isobutylphenyl)ethyl>-1H-benzimidazole 、 邻乙酰水杨酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到2-({2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazol-1-yl}carbonyl)phenyl acetate
  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
• 作为产物：
  描述：

  N-(2-aminophenyl)-2-(4-isobutylphenyl)propanamide 在 溶剂黄146 作用下， 反应 4.0h， 以90%的产率得到2-<1-(4-isobutylphenyl)ethyl>-1H-benzimidazole
  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

• Singh; Hingorani; Trivedi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 6, p. 596 - 597
  作者：Singh、Hingorani、Trivedi、Vora

  DOI：——

  日期：——
• PRITPAL, SINGH;HINGORANI, L. L.;TRIVEDI, G. K.;VORA, JYOTI, INDIAN J. CHEM. B, 29,(1990) N, C. 596-597
  作者：PRITPAL, SINGH、HINGORANI, L. L.、TRIVEDI, G. K.、VORA, JYOTI

  DOI：——

  日期：——
• US6712262B2
  申请人：——

  公开号：US6712262B2

  公开（公告）日：2004-03-30
• 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.