1-(2-溴乙基)-2-甲基-1H-苯并咪唑 | 286407-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 1-(2-溴乙基)-2-甲基-1H-苯并咪唑
• 英文名称: 1-(2-bromoethyl)-2-methyl-1H-benzimidazole
• 英文别名: 1-(2-Bromo-1-ethyl)-2-methylbenzimidazole；1-(2-bromoethyl)-2-methyl-1H-1,3-benzodiazole；1-(2-bromoethyl)-2-methylbenzimidazole
• CAS: 286407-95-2
• 化学式: C₁₀H₁₁BrN₂
• mdl: MFCD00457747
• 分子量: 239.115
• InChiKey: VCPOOQOJBVTOGU-UHFFFAOYSA-N

物化性质

• 沸点：
  360.0±25.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 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：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2-溴乙基)-2-甲基-1H-苯并咪唑 、 6-(4-吗啉)-1H-嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 以53.6%的产率得到4-(9-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)ethyl)-9H-purin-6-yl)morpholine
  参考文献：
  名称：

  Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove

  摘要：

  A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus ( MIC = 4 mu g/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c-DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.046
• 作为产物：
  描述：

  邻苯二胺 在 盐酸 、 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 生成 1-(2-溴乙基)-2-甲基-1H-苯并咪唑
  参考文献：
  名称：

  Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove

  摘要：

  A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus ( MIC = 4 mu g/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c-DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.046

文献信息

• <i>N</i>-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2<i>E</i>)-<i>N</i>-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1<i>H</i>-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)
  作者：Stacy W. Remiszewski、Lidia C. Sambucetti、Kenneth W. Bair、John Bontempo、David Cesarz、Nagarajan Chandramouli、Ru Chen、Min Cheung、Susan Cornell-Kennon、Karl Dean、George Diamantidis、Dennis France、Michael A. Green、Kobporn Lulu Howell、Rina Kashi、Paul Kwon、Peter Lassota、Mary S. Martin、Yin Mou、Lawrence B. Perez、Sushil Sharma、Troy Smith、Eric Sorensen、Francis Taplin、Nancy Trogani、Richard Versace、Heather Walker、Susan Weltchek-Engler、Alexander Wood、Arthur Wu、Peter Atadja

  DOI：10.1021/jm030235w

  日期：2003.10.1

  A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.
• McClure, James R.; Custer, John H.; Schwarz, H. Dean, Synlett, 2000, # 5, p. 710 - 712
  作者：McClure, James R.、Custer, John H.、Schwarz, H. Dean、Lill, Deborah A.

  DOI：——

  日期：——
• Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove
  作者：Ya-Nan Wang、Rammohan R. Yadav Bheemanaboina、Gui-Xin Cai、Cheng-He Zhou

  DOI：10.1016/j.bmcl.2018.03.046

  日期：2018.5

  A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus ( MIC = 4 mu g/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c-DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity. (C) 2018 Elsevier Ltd. All rights reserved.