5,6-dibromo-2-propyl-1H-benzo[d]imidazole | 176949-19-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5,6-dibromo-2-propyl-1H-benzo[d]imidazole
• 英文别名: 5,6-dibromo-2-propyl-1H-benzimidazole
• CAS: 176949-19-2
• 化学式: C₁₀H₁₀Br₂N₂
• 分子量: 318.011
• InChiKey: DOUUGDYRPPPVIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  5,6-dibromo-2-propyl-1H-benzo[d]imidazole 、 2-氰基-4'-溴甲基联苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以87%的产率得到4'-[(5,6-dibromo-2-propyl-1H-benzo[d]imidazol-1-yl)methyl]-biphenyl-2-carbonitrile
  参考文献：
  名称：

  Characterization of new PPARγ agonists: Benzimidazole derivatives—importance of positions 5 and 6, and computational studies on the binding mode

  摘要：

  In this and previous studies we investigated the importance of partial structures of Telmisartan on PPAR gamma activation. The biphenyl-4-ylmethyl moiety at N1 and residues at C2 of the central benzimidazole were identified to be essential for receptor activation and potency of receptor binding. Now we focused our attention on positions 5 and 6 of the central benzimidazole and introduced bromine (3b-5/6, 3c), phenylcarbonyl (3d-5/6), hydroxy(phenyl) methyl (3g-5/6), hydroxymethyl (3h-5/6) and formyl (3i) groups. The selection of these moieties was inspired by the structure of Losartan and its metabolite EXP3179. In order to increase the hydrophobicity of the central part of the molecule, the benzimidazole was exchanged by a naphtho[2,3-d] imidazole (5). The compounds 3a-3i and 5 were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay using COS-7 cells, transiently transfected with pGal4-hPPAR gamma DEF, pGal5-TK-pGL3 and pRL-CMV, as established models for the assessment of cellular PPAR gamma activation. An enhanced effect on PPAR gamma activation could be observed if lipophilic moieties are introduced in these positions. 4 '-[(2-Propyl-1H-naphtho[2,3-d] imidazol-1-yl) methyl] biphenyl-2-carboxylic acid (5) was identified as the most potent compound with an EC50 of 0.26 mu M and the profile of a full agonist.Together with compounds of the former structure-activity relationship study (position 2-substituted benzimidazole derivatives 4a-4j), the binding mode of Telmisartan and its derivatives have been analyzed in 3D pharmacophore-driven docking experiments. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.102
• 作为产物：
  描述：

  原丁酸三甲酯 、 4,5-二溴-1,2-苯二胺 在 盐酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 以90%的产率得到5,6-dibromo-2-propyl-1H-benzo[d]imidazole
  参考文献：
  名称：

  Characterization of new PPARγ agonists: Benzimidazole derivatives—importance of positions 5 and 6, and computational studies on the binding mode

  摘要：

  In this and previous studies we investigated the importance of partial structures of Telmisartan on PPAR gamma activation. The biphenyl-4-ylmethyl moiety at N1 and residues at C2 of the central benzimidazole were identified to be essential for receptor activation and potency of receptor binding. Now we focused our attention on positions 5 and 6 of the central benzimidazole and introduced bromine (3b-5/6, 3c), phenylcarbonyl (3d-5/6), hydroxy(phenyl) methyl (3g-5/6), hydroxymethyl (3h-5/6) and formyl (3i) groups. The selection of these moieties was inspired by the structure of Losartan and its metabolite EXP3179. In order to increase the hydrophobicity of the central part of the molecule, the benzimidazole was exchanged by a naphtho[2,3-d] imidazole (5). The compounds 3a-3i and 5 were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay using COS-7 cells, transiently transfected with pGal4-hPPAR gamma DEF, pGal5-TK-pGL3 and pRL-CMV, as established models for the assessment of cellular PPAR gamma activation. An enhanced effect on PPAR gamma activation could be observed if lipophilic moieties are introduced in these positions. 4 '-[(2-Propyl-1H-naphtho[2,3-d] imidazol-1-yl) methyl] biphenyl-2-carboxylic acid (5) was identified as the most potent compound with an EC50 of 0.26 mu M and the profile of a full agonist.Together with compounds of the former structure-activity relationship study (position 2-substituted benzimidazole derivatives 4a-4j), the binding mode of Telmisartan and its derivatives have been analyzed in 3D pharmacophore-driven docking experiments. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.102

文献信息

• Characterization of new PPARγ agonists: Benzimidazole derivatives—importance of positions 5 and 6, and computational studies on the binding mode
  作者：Matthias Goebel、Gerhard Wolber、Patrick Markt、Bart Staels、Thomas Unger、Ulrich Kintscher、Ronald Gust

  DOI：10.1016/j.bmc.2010.06.102

  日期：2010.8

  In this and previous studies we investigated the importance of partial structures of Telmisartan on PPAR gamma activation. The biphenyl-4-ylmethyl moiety at N1 and residues at C2 of the central benzimidazole were identified to be essential for receptor activation and potency of receptor binding. Now we focused our attention on positions 5 and 6 of the central benzimidazole and introduced bromine (3b-5/6, 3c), phenylcarbonyl (3d-5/6), hydroxy(phenyl) methyl (3g-5/6), hydroxymethyl (3h-5/6) and formyl (3i) groups. The selection of these moieties was inspired by the structure of Losartan and its metabolite EXP3179. In order to increase the hydrophobicity of the central part of the molecule, the benzimidazole was exchanged by a naphtho[2,3-d] imidazole (5). The compounds 3a-3i and 5 were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay using COS-7 cells, transiently transfected with pGal4-hPPAR gamma DEF, pGal5-TK-pGL3 and pRL-CMV, as established models for the assessment of cellular PPAR gamma activation. An enhanced effect on PPAR gamma activation could be observed if lipophilic moieties are introduced in these positions. 4 '-[(2-Propyl-1H-naphtho[2,3-d] imidazol-1-yl) methyl] biphenyl-2-carboxylic acid (5) was identified as the most potent compound with an EC50 of 0.26 mu M and the profile of a full agonist.Together with compounds of the former structure-activity relationship study (position 2-substituted benzimidazole derivatives 4a-4j), the binding mode of Telmisartan and its derivatives have been analyzed in 3D pharmacophore-driven docking experiments. (C) 2010 Elsevier Ltd. All rights reserved.