methyl 5-chloro-2-(2-(cyclohexylamino)-1-(1-(3-fluorophenyl)cyclopropyl)-2-oxoethylamino)phenylcarbamate | 1444176-02-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 5-chloro-2-(2-(cyclohexylamino)-1-(1-(3-fluorophenyl)cyclopropyl)-2-oxoethylamino)phenylcarbamate
• CAS: 1444176-02-6
• 化学式: C₂₂H₂₅Cl₂N₃O₃
• 分子量: 450.365
• InChiKey: BOZAOFSKKDVYFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.77
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.46
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 5-chloro-2-(2-(cyclohexylamino)-1-(1-(3-fluorophenyl)cyclopropyl)-2-oxoethylamino)phenylcarbamate 在 1,5,7-三氮杂双环[4.4.0]癸-5-烯 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以31%的产率得到2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-2-(4-chlorophenyl)-N-cyclohexylacetamide
  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
• 作为产物：
  描述：

  2-硝基-5-氯苯胺 在 iron(III) chloride 、 苯膦酸 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 methyl 5-chloro-2-(2-(cyclohexylamino)-1-(1-(3-fluorophenyl)cyclopropyl)-2-oxoethylamino)phenylcarbamate
  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