2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-N-cyclohexyl-2-(naphthalen-1-yl)acetamide | 1444176-16-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-N-cyclohexyl-2-(naphthalen-1-yl)acetamide
• 英文别名: 2-(5-chloro-2-oxo-3H-benzimidazol-1-yl)-N-cyclohexyl-2-naphthalen-1-ylacetamide
• CAS: 1444176-16-2
• 化学式: C₂₅H₂₄ClN₃O₂
• 分子量: 433.937
• InChiKey: BSCYMGRYOCBKTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  methyl 5-chloro-2-nitrophenylcarbamate 在 iron(III) chloride 、 苯膦酸 、 potassium carbonate 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-N-cyclohexyl-2-(naphthalen-1-yl)acetamide
  参考文献：
  名称：

  Benzimidazole-2-one: A novel anchoring principle for antagonizing p53-Mdm2

  摘要：

  Herein we propose the benzimidazole-2-one substructure as a suitable tryptophan mimic and thus a reasonable starting point for the design of p53 Mdm2 antagonists. We devise a short multicomponent reaction route to hitherto unknown 2-(2-oxo-2,3-dihydro-1H-benzoidlimidazol-1-yl)acetamides by reacting mono N-carbamate protected phenylenediamine in a Ugi-3 CR followed by base induced cyclisation. Our preliminary synthesis and screening results are presented here. The finding of the benzimidazolone moiety as a tryptophan replacement in mdm2 is significant as it offers access to novel scaffolds with potentially higher selectivitY and potency and improved biological activities. Observing low mu M affinities to mdm2 by NMR and fluorescence polarization we conclude that the 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamide scaffold might be a good starting point to further optimize the affinities to Mdm2. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.020

文献信息

• Benzimidazole-2-one: A novel anchoring principle for antagonizing p53-Mdm2
  作者：Wei Wang、Haiping Cao、Siglinde Wolf、Miguel S. Camacho-Horvitz、Tad A. Holak、Alexander Dömling

  DOI：10.1016/j.bmc.2012.06.020

  日期：2013.7

  Herein we propose the benzimidazole-2-one substructure as a suitable tryptophan mimic and thus a reasonable starting point for the design of p53 Mdm2 antagonists. We devise a short multicomponent reaction route to hitherto unknown 2-(2-oxo-2,3-dihydro-1H-benzoidlimidazol-1-yl)acetamides by reacting mono N-carbamate protected phenylenediamine in a Ugi-3 CR followed by base induced cyclisation. Our preliminary synthesis and screening results are presented here. The finding of the benzimidazolone moiety as a tryptophan replacement in mdm2 is significant as it offers access to novel scaffolds with potentially higher selectivitY and potency and improved biological activities. Observing low mu M affinities to mdm2 by NMR and fluorescence polarization we conclude that the 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamide scaffold might be a good starting point to further optimize the affinities to Mdm2. (C) 2012 Elsevier Ltd. All rights reserved.