2-chloro-1-(4-methylbenzyl)-1H-benzo[d]imidazole | 388574-59-2

• 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: 2-chloro-1-(4-methylbenzyl)-1H-benzo[d]imidazole
• 英文别名: 2-chloro-1-(4-methylbenzyl)benzimidazole；2-Chloro-1-(4-methylbenzyl)-1H-benzimidazole；2-chloro-1-[(4-methylphenyl)methyl]benzimidazole
• CAS: 388574-59-2
• 化学式: C₁₅H₁₃ClN₂
• 分子量: 256.735
• InChiKey: NVTJNBWKCVKUBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-1-(4-methylbenzyl)-1H-benzo[d]imidazole 在 盐酸 、 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 5.0h， 生成 2-[10-[(4-Methylphenyl)methyl]-3,4-dioxo-[1,2,4]triazino[4,3-a]benzimidazol-2-yl]acetic acid
  参考文献：
  名称：

  [1,2,4]Triazino[4,3-a]benzimidazole Acetic Acid Derivatives:  A New Class of Selective Aldose Reductase Inhibitors

  摘要：

  Acetic acid derivatives of [1,2,4]triazino[4,3-alpha ]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-alpha ]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC50 = 0.36 muM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational. changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.

  DOI：

  10.1021/jm0109210
• 作为产物：
  描述：

  2-氯苯并咪唑 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-chloro-1-(4-methylbenzyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  5-HT3R Binding of lerisetron: an interdisciplinary approach to drug–Receptor interactions

  摘要：

  The design, synthesis, and use of lerisetron-based molecular probes to investigate the 5-HT3R binding site are described. A SAR study, which involved distance and electronic parameter modifications of lerisetron's N-benzyl group, resulted in the discovery of a partial agonist. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00417-6

文献信息

• Metal-free, highly efficient organocatalytic amination of benzylic C–H bonds
  作者：Qicai Xue、Jin Xie、Huamin Li、Yixiang Cheng、Chengjian Zhu

  DOI：10.1039/c3cc41558a

  日期：——

  A new synthetic approach toward direct C–N bond formation through sp3 C–H activation has been developed under metal-free conditions. Both primary and secondary benzylic C–H substrates could react smoothly with various amines to give only mono-amination products with good to excellent yields.

  在无金属条件下,已开发出一种通过sp3 C-H活化实现直接C-N键形成的新型合成方法。初级和次级苄基C-H底物都能与各种胺类发生反应,只生成单胺化产物,产率从良好到优秀。
• Brain-penetrating 2-aminobenzimidazole H1-antihistamines for the treatment of insomnia
  作者：Timothy Coon、Wilna J. Moree、Binfeng Li、Jinghua Yu、Said Zamani-Kord、Siobhan Malany、Mark A. Santos、Lisa M. Hernandez、Robert E. Petroski、Aixia Sun、Jenny Wen、Sue Sullivan、Jason Haelewyn、Michael Hedrick、Samuel J. Hoare、Margaret J. Bradbury、Paul D. Crowe、Graham Beaton

  DOI：10.1016/j.bmcl.2009.05.086

  日期：2009.8

  The benzimidazole core of the selective non-brain-penetrating H-1-antihistamine mizolastine was used to identify a series of brain-penetrating H-1-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H-1-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro pro. le. (C) 2009 Elsevier Ltd. All rights reserved.
• [1,2,4]Triazino[4,3-<i>a</i>]benzimidazole Acetic Acid Derivatives:  A New Class of Selective Aldose Reductase Inhibitors
  作者：Federico Da Settimo、Giampaolo Primofiore、Antonio Da Settimo、Concettina La Motta、Sabrina Taliani、Francesca Simorini、Ettore Novellino、Giovanni Greco、Antonio Lavecchia、Enrico Boldrini

  DOI：10.1021/jm0109210

  日期：2001.12.1

  Acetic acid derivatives of [1,2,4]triazino[4,3-alpha ]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-alpha ]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC50 = 0.36 muM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational. changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.
• 5-HT3R Binding of lerisetron: an interdisciplinary approach to drug–Receptor interactions
  作者：Harish S. Parihar、Asha Suryanarayanan、Chun Ma、Prasad Joshi、Padma Venkataraman、Marvin K. Schulte、Karen S. Kirschbaum

  DOI：10.1016/s0960-894x(01)00417-6

  日期：2001.8

  The design, synthesis, and use of lerisetron-based molecular probes to investigate the 5-HT3R binding site are described. A SAR study, which involved distance and electronic parameter modifications of lerisetron's N-benzyl group, resulted in the discovery of a partial agonist. (C) 2001 Elsevier Science Ltd. All rights reserved.