phenyl(2-propyl-1H-benzo[d]imidazol-6-yl)methanone | 185980-48-7

• 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: phenyl(2-propyl-1H-benzo[d]imidazol-6-yl)methanone
• 英文别名: phenyl-(2-propyl-1H-benzoimidazol-5-yl)methanone；phenyl-(2-propyl-3H-benzimidazol-5-yl)methanone
• CAS: 185980-48-7
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: IYFZJUZDDCWNCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  phenyl(2-propyl-1H-benzo[d]imidazol-6-yl)methanone 、 3,4-二氯苄溴 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到[1-(3,4-Dichloro-benzyl)-2-propyl-1H-benzoimidazol-5-yl]-phenyl-methanone
  参考文献：
  名称：

  Benzimidazole derivatives

  摘要：

  本文揭示了以下式I或II的化合物：其中R是烷基苯或取代苯基；R2是氢、卤素、烷氧基或烷基；R1是氢、烷基、芳基、芳基烷基或取代苄基；或其药用可接受的盐，这些化合物可用作平滑肌细胞增殖的抑制剂。

  公开号：

  US06288100B1
• 作为产物：
  描述：

  原丁酸三甲酯 、 3,4-二氨基二苯甲酮 在 盐酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 以85%的产率得到phenyl(2-propyl-1H-benzo[d]imidazol-6-yl)methanone
  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

• A General Approach to Substituted Benzimidazoles and Benzoxazoles <i>via</i> Heterogeneous Palladium‐Catalyzed Hydrogen‐Transfer with Primary Amines
  作者：Marianna Pizzetti、Elisa De Luca、Elena Petricci、Andrea Porcheddu、Maurizio Taddei

  DOI：10.1002/adsc.201200253

  日期：2012.9.17

  employed. Primary amines are the most suitable reagents for the atom economy of the overall process that resulted to be general as several different substituted benzimidazoles were obtained in good yield. Benzoxazoles can be also prepared starting from primary amines and o‐aminophenol. The reaction is also highly selective as no (poly)‐alkylated phenylenediamines or cross‐contaminated benzimidazoles are

  据报道，在钯/炭存在下，以邻苯二胺和胺为原料合成苯并咪唑。在微波电介质加热，可以使用叔胺，仲，和甚至伯胺作为底物为钯-介导的过程中得到的2-取代的或1,2-二取代的苯并咪唑，取决于性质ø -使用的苯二胺。对于整个过程的原子经济性而言，伯胺是最合适的试剂，由于获得了数种不同的取代苯并咪唑类，它们的收率很高，因此普遍使用。苯并恶唑也可以从伯胺和邻氨基苯甲酸开始制备氨基苯酚 由于没有从（N-单烷基苯二胺）获得（多）烷基化的苯二胺或交叉污染的苯并咪唑，该反应的选择性也很高。这种行为被解释为与N-烷基芳基胺的芳族NH键连接的亚甲基脱氢的稀缺性。实验进行了同意，以画出过程中发生的反应路径的几乎完整图景。催化剂可以循环使用几次，尽管远未达到最佳性能，但催化剂TON = 90对于进一步的大规模优化方案是令人鼓舞的。此外，上的木炭催化微波辅助反应在钯Ò苯二胺使叔胺脱烷基并转化为仲胺。
• BENZIMIDAZOLE DERIVATIVES AS INHIBITORS OF SMOOTH MUSCLE CELL PROLIFERATION
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0830343A1

  公开（公告）日：1998-03-25
• US6288100B1
  申请人：——

  公开号：US6288100B1

  公开（公告）日：2001-09-11
• [EN] BENZIMIDAZOLE DERIVATIVES AS INHIBITORS OF SMOOTH MUSCLE CELL PROLIFERATION<br/>[FR] DERIVES DE BENZIMIDAZOLE INHIBITEURS DE LA PROLIFERATION DES CELLULES MUSCULAIRES LISSES
  申请人：——

  公开号：WO1996039390A1

  公开（公告）日：1996-12-12

  [EN] Disclosed herein are compounds and pharmaceutically acceptable salts of compounds of formula (I) or (II), wherein R is alkyl, phenyl or substituted phenyl; R2 is hydrogen, halogen, alkoxy or alkyl; R1 is hydrogen, alkyl, aryl, arylalkyl, or substituted benzyl; which are useful as inhibitors of smooth muscle cell proliferation.
  [FR] Composés et sels pharmaceutiquement acceptables de composés de formule (I) ou (II), dans lesquelles R est alkyle, phényle ou phényle substitué, R2 est hydrogène, halogène, alcoxy ou alkyle, R1 est hydrogène, alkyle, aryle, arylalkyle ou benzyle substitué. Ces substances sont utiles comme inhibiteurs de la prolifération des cellules musculaires lisses.
• 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.