methyl N-(2-amino-4-fluorophenyl)carbamate | 1019389-20-8

• 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: methyl N-(2-amino-4-fluorophenyl)carbamate
• CAS: 1019389-20-8
• 化学式: C₈H₉FN₂O₂
• 分子量: 184.17
• InChiKey: RWOWNSVTDYWTEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl N-(2-amino-4-fluorophenyl)carbamate 、 1-异氰基-2-甲基丙烷 、 4-氯苯甲醛 在 苯膦酸 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以45%的产率得到methyl 2-(1-(4-chlorophenyl)-2-(isobutylamino)-2-oxoethylamino)-4-fluorophenylcarbamate
  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.