2-hydrazono-3-phenylpropanoic acid | 59587-12-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-hydrazono-3-phenylpropanoic acid
• 英文别名: Phenylbrenztraubensaeure-hydrazon；2-hydrazinylidene-3-phenylpropanoic acid
• CAS: 59587-12-1
• 化学式: C₉H₁₀N₂O₂
• 分子量: 178.191
• InChiKey: WPOOABJYOKEKLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.63
• 重原子数：
  13.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.68
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  苯丙酮酸 在 肼 、 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以62%的产率得到2-hydrazono-3-phenylpropanoic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)

  摘要：

  C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 mu M). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 mu M) and 3-chloro- (IC50 = 0.17 mu M) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.037

文献信息

• Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)
  作者：Sudha Korwar、Benjamin L. Morris、Hardik I. Parikh、Robert A. Coover、Tyler W. Doughty、Ian M. Love、Brendan J. Hilbert、William E. Royer、Glen E. Kellogg、Steven R. Grossman、Keith C. Ellis

  DOI：10.1016/j.bmc.2016.04.037

  日期：2016.6

  C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 mu M). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 mu M) and 3-chloro- (IC50 = 0.17 mu M) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer. (C) 2016 Elsevier Ltd. All rights reserved.