4'-[(2-propyl-1H-naphth[2,3-d]imidazol-1-yl)methyl]-biphenyl-2-carboxylic acid | 133142-35-5

• 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: 4'-[(2-propyl-1H-naphth[2,3-d]imidazol-1-yl)methyl]-biphenyl-2-carboxylic acid
• 英文别名: 4'-[(2-n-Propyl-naphtho[2,3-d]imidazol-1-yl)-methyl]biphenyl-2-carboxylic acid；2-[4-[(2-propylbenzo[f]benzimidazol-3-yl)methyl]phenyl]benzoic acid
• CAS: 133142-35-5
• 化学式: C₂₈H₂₄N₂O₂
• 分子量: 420.511
• InChiKey: FBEQJIXUAGEQMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4'-[(2-propyl-1H-naphth[2,3-d]imidazol-1-yl)methyl]biphenyl-2-carbonitrile 在 水 、 potassium hydroxide 、 盐酸 作用下， 以 乙二醇 、 水 为溶剂， 反应 0.25h， 以91%的产率得到4'-[(2-propyl-1H-naphth[2,3-d]imidazol-1-yl)methyl]-biphenyl-2-carboxylic acid
  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

• Benzimidazoles and medicaments containing these compounds
  申请人：Dr. Karl Thomae GmbH

  公开号：US05541229A1

  公开（公告）日：1996-07-30

  The invention relates to benzimidazoles of the formula ##STR1## in which R.sub.1 to R.sub.2 are as defined in claim 1, 1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. In particular, the novel compounds are angiotensin II antagonists.

  该发明涉及公式##STR1##中的苯并咪唑，其中R.sub.1至R.sub.2如权利要求书中定义，1和3为其异构体混合物及其盐，具有有价值的性质。特别是，这些新化合物是血管紧张素II拮抗剂。
• Benzimidazoles, medicaments containing these compounds and processes for
  申请人：Karl Thomae GmbH

  公开号：US05864043A1

  公开（公告）日：1999-01-26

  The invention relates to benzimidazoles of the formula ##STR1## in which R.sub.1 to R.sub.4 are as defined in claim 1, 1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. In particular, the novel compounds are angiotensin II antagonists.

  本发明涉及式为##STR1##的苯并咪唑，其中R.sub.1至R.sub.4如权利要求1所定义，1和3的异构体混合物及其加合盐具有有价值的性质。特别是，这些新型化合物是血管紧张素II受体拮抗剂。
• Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
  申请人：Dr. Karl Thomae GmbH

  公开号：EP0392317A2

  公开（公告）日：1990-10-17

  Die Erfindung betrifft Benzimidazole der Formel in der R₁ bis R₆ wie im Anspruch 1 definiert sind, deren 1-, 3-Isomerengemische und deren Additionssalze, welche wertvolle Eigenschaften aufweisen. Die neuen Verbindungen stellen insbesondere Angiotensin-II-­Antagonisten dar.

  本发明涉及式如下的苯并咪唑类化合物 其中 R₁至 R₆如权利要求 1 所定义，它们的 1-、3-异构体混合物及其加成盐具有宝贵的特性。 特别是，这些新化合物是血管紧张素 II 拮抗剂。
• US5541229A
  申请人：——

  公开号：US5541229A

  公开（公告）日：1996-07-30
• 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.