1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1H-benzo[d]imidazole | 1382488-15-4

• 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: 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1H-benzo[d]imidazole
• 英文别名: 1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-5-methoxy-1H-benzimidazole；1-[(2-Chlorophenyl)methyl]-5-methoxy-2-[1-[4-(2-methylpropyl)phenyl]ethyl]benzimidazole
• CAS: 1382488-15-4
• 化学式: C₂₇H₂₉ClN₂O
• 分子量: 432.993
• InChiKey: JPEJCNWUFQHFCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1H-benzo[d]imidazole 在 氢溴酸 、 四丁基碘化铵 、 caesium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-5-(pyridin-2-ylmethoxy)-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
• 作为产物：
  描述：

  2-(4-异丁基苯基)丙酰氯 在 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1H-benzo[d]imidazole
  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

• Synthesis and biological evaluation of C(5)-substituted derivatives of leukotriene biosynthesis inhibitor BRP-7
  作者：Serkan Levent、Jana Gerstmeier、Abdurrahman Olgaç、Felix Nikels、Ulrike Garscha、Andrea Carotti、Antonio Macchiarulo、Oliver Werz、Erden Banoglu、Burcu Çalışkan

  DOI：10.1016/j.ejmech.2016.07.004

  日期：2016.10

  atherosclerosis. Here we describe the synthesis of a series of C(5)-substituted analogues of the previously described 5-LO-activating protein (FLAP) inhibitor BRP-7 (IC50 = 0.31 muM) to explore the effects of substitution at the C(5)-benzimidazole (BI) ring as a strategy to increase the potency against FLAP-mediated 5-LO product formation. Incorporation of polar substituents on the C(5) position of the BI core

  用5-脂氧合酶（5-LO）途径进行药理干预可抑制白三烯（LT）生物合成，这是经临床验证的策略，可用于治疗呼吸道和心血管疾病，例如哮喘和动脉粥样硬化。在这里我们描述了先前描述的5-LO激活蛋白（FLAP）抑制剂BRP-7（IC50 = 0.31μM）的一系列C（5）取代类似物的合成，以探讨在C（5 ）-苯并咪唑（BI）环作为增加针对FLAP介导的5-LO产物形成的效力的策略。在BI核的C（5）位置上掺入极性取代基，例如具有C（5）-腈取代基的化合物11，可显着增强抑制人类嗜中性粒细胞中5-LO产物合成的能力（IC50 = 0.07μM ）和单核细胞（IC50 = 0.026μM）。
• COMPOUNDS AND METHODS FOR TREATMENT OF HEDGEHOG PATHWAY ASSOCIATED CONDITIONS
  申请人：Suzhou Mednes Pharma Tech Co., Ltd.

  公开号：EP3810573A1

  公开（公告）日：2021-04-28
• 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.