phenyl 4-fluoro-3-nitrobenzoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: phenyl 4-fluoro-3-nitrobenzoate
• 英文别名: Phenyl 4-fluoro-3-nitrobenzoate
• 化学式: C₁₃H₈FNO₄
• 分子量: 261.209
• InChiKey: YVGPCSAGLCIXFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenyl 4-fluoro-3-nitrobenzoate 在 吡啶 、 tin(II) chloride dihdyrate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 phenyl 3-(2-chloro-4-fluoro-3-methyl-5-nitrobenzamido)-4-(4-methylpiperazin-1-yl) benzoate
  参考文献：
  名称：

  Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)–WDR5 interaction

  摘要：

  WDR5 is an essential protein for enzymatic activity of MLL1. Targeting the protein-protein interaction (PPI) between MLL1 and WDR5 represents a new potential therapeutic strategy for MLL leukemia. Based on the structure of reported inhibitor WDR5-0103, a class of ester compounds were designed and synthetized to disturb MLL1-WDR5 PPI. These inhibitors efficiently inhibited the histone methyltransferase activity in vitro. Especially, WL-15 was one of the most potent inhibitors, blocking the interaction of MLL1-WDR5 with IC50 value of 26.4 nM in competitive binding assay and inhibiting the catalytic activity of MLL1 complex with IC50 value of 5.4 mu M. Docking model indicated that ester compounds suitably occupied the central cavity of WDR5 protein and recapitulated the interactions of WDR5-0103 and the hydrophobic groups and key amino greatly increased the activity in blocking MLL1-WDR5 PPI. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.073
• 作为产物：
  描述：

  4-氟-3-硝基苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 phenyl 4-fluoro-3-nitrobenzoate
  参考文献：
  名称：

  Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)–WDR5 interaction

  摘要：

  WDR5 is an essential protein for enzymatic activity of MLL1. Targeting the protein-protein interaction (PPI) between MLL1 and WDR5 represents a new potential therapeutic strategy for MLL leukemia. Based on the structure of reported inhibitor WDR5-0103, a class of ester compounds were designed and synthetized to disturb MLL1-WDR5 PPI. These inhibitors efficiently inhibited the histone methyltransferase activity in vitro. Especially, WL-15 was one of the most potent inhibitors, blocking the interaction of MLL1-WDR5 with IC50 value of 26.4 nM in competitive binding assay and inhibiting the catalytic activity of MLL1 complex with IC50 value of 5.4 mu M. Docking model indicated that ester compounds suitably occupied the central cavity of WDR5 protein and recapitulated the interactions of WDR5-0103 and the hydrophobic groups and key amino greatly increased the activity in blocking MLL1-WDR5 PPI. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.073

文献信息

• Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)–WDR5 interaction
  作者：Dong-Dong Li、Zhi-Hui Wang、Wei-Lin Chen、Yi-Yue Xie、Qi-Dong You、Xiao-Ke Guo

  DOI：10.1016/j.bmc.2016.09.073

  日期：2016.11

  WDR5 is an essential protein for enzymatic activity of MLL1. Targeting the protein-protein interaction (PPI) between MLL1 and WDR5 represents a new potential therapeutic strategy for MLL leukemia. Based on the structure of reported inhibitor WDR5-0103, a class of ester compounds were designed and synthetized to disturb MLL1-WDR5 PPI. These inhibitors efficiently inhibited the histone methyltransferase activity in vitro. Especially, WL-15 was one of the most potent inhibitors, blocking the interaction of MLL1-WDR5 with IC50 value of 26.4 nM in competitive binding assay and inhibiting the catalytic activity of MLL1 complex with IC50 value of 5.4 mu M. Docking model indicated that ester compounds suitably occupied the central cavity of WDR5 protein and recapitulated the interactions of WDR5-0103 and the hydrophobic groups and key amino greatly increased the activity in blocking MLL1-WDR5 PPI. (C) 2016 Elsevier Ltd. All rights reserved.