N-hydroxy-4-((((3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)amino)methyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-hydroxy-4-((((3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)amino)methyl)benzamide
• 英文别名: N-hydroxy-4-[[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methylamino]methyl]benzamide
• 化学式: C₁₈H₁₅F₃N₄O₃
• 分子量: 392.337
• InChiKey: YGVKLOQEGNQXDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  对三氟甲基苯腈 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 盐酸羟胺 、 羟胺 、 氯甲酸乙酯 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 50.5h， 生成 N-hydroxy-4-((((3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)amino)methyl)benzamide
  参考文献：
  名称：

  Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors

  摘要：

  Using Entinostat as a lead compound, 2-aminobenzamide and hydroxamate derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro anti-proliferative activities using the MTT-based assay against five human cancer cell lines including U937, A549, NCI-H661, MDA-MB-231 and HCT116. 2-Aminobenzamide series of compounds (10a-10j) demonstrated the most significant inhibition against human acute monocytic myeloid leukemia cell line U937, but no or poor activities against two human lung cancer cell lines. Furthermore, the target compounds were screened for their inhibitory activities against HDAC 1, 2, and 8. 2-Aminobenzamide derivatives (10) manifested a higher selectivity for HDAC 1 over HDAC 2, but were not active against HDAC 8. In contrast, most hydroxamate derivatives (11) inhibit HDAC 8 with lower IC50 values than SAHA and Entinostat. Docking study with selected compounds 10f and ha revealed that the compounds might bind tightly to the binding pockets in HDAC 2 and HDAC 8, respectively. The results suggest that they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting HDACs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.002