3-(4-fluorophenyl)-2-hydroxyacrylic acid | 111649-73-1

• 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: 3-(4-fluorophenyl)-2-hydroxyacrylic acid
• 英文别名: 3-(4-Fluorophenyl)-2-hydroxy-2-propenoic acid；3-(4-fluorophenyl)-2-hydroxyprop-2-enoic acid
• CAS: 111649-73-1
• 化学式: C₉H₇FO₃
• 分子量: 182.151
• InChiKey: SOBWLKLZARZQOX-UHFFFAOYSA-N

物化性质

• 熔点：
  163-164 °C
• 沸点：
  341.2±42.0 °C(Predicted)
• 密度：
  1.439±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-2-hydroxyacrylic acid 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 12.0h， 以74%的产率得到3-(4-fluorophenyl)-2-(hydroxyimino)propanoic 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
• 作为产物：
  描述：

  2,4-Imidazolidinedione, 5-[(4-fluorophenyl)methylene]-, (Z)- 在 水 、 sodium hydroxide 作用下， 反应 12.0h， 生成 3-(4-fluorophenyl)-2-hydroxyacrylic acid
  参考文献：
  名称：

  评估丙酮酸羧化酶抑制剂α-羟基肉桂酸。

  摘要：

  通过基于结构的药物设计项目（SBDD），发现了有效的丙酮酸羧化酶小分子抑制剂（PC）。制备了一系列α-酮酸（7）和α-羟基肉桂酸（8），并在两种测定中评估了其对PC的抑制作用。两种最有效的抑制剂是3,3'-（1,4-亚苯基）双[2-羟基-2-丙酸]（8u）和2-羟基-3-（喹啉-2-基）丙酸（8v））的IC 50值分别为3.0±1.0μM和4.3±1.5μM。化合物8v是相对于丙酮酸（K i = 0.74μM）和针对ATP的混合型抑制剂，表明它靶向PC的独特羧基转移酶（CT）域。此外，化合物8v不会显着抑制人碳酸酐酶II，基质金属蛋白酶-2，苹果酸脱氢酶或乳酸脱氢酶。

  DOI：

  10.1016/j.bmc.2019.07.027

文献信息

• Structure activity relationship studies on rhodanines and derived enethiol inhibitors of metallo-β-lactamases
  作者：Dong Zhang、Marios S. Markoulides、Dmitrijs Stepanovs、Anna M. Rydzik、Ahmed El-Hussein、Corentin Bon、Jos J.A.G. Kamps、Klaus-Daniel Umland、Patrick M. Collins、Samuel T. Cahill、David Y. Wang、Frank von Delft、Jürgen Brem、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1016/j.bmc.2018.02.043

  日期：2018.7

  antibiotics. We report studies on enethiol containing MBL inhibitors, which were prepared by rhodanine hydrolysis. The enethiols inhibit MBLs from different subclasses. Crystallographic analyses reveal that the enethiol sulphur displaces the di-Zn(II) ion bridging 'hydrolytic' water. In some, but not all, cases biophysical analyses provide evidence that rhodanine/enethiol inhibition involves formation

  金属-β-内酰胺酶 (MBL) 使细菌对几乎所有类别的 β-内酰胺抗生素产生耐药性。我们报告了通过绕丹宁水解制备的含烯硫醇的 MBL 抑制剂的研究。烯硫醇抑制不同亚类的 MBL。晶体分析表明，烯硫醇硫取代了桥接“水解”水的二锌 (II) 离子。在某些（但不是全部）情况下，生物物理分析提供证据表明绕丹宁/烯硫醇抑制涉及三元 MBL 烯硫醇绕丹宁复合物的形成。结果证明低分子量活性位点 Zn(II) 螯合化合物如何抑制一系列临床相关的 MBL，并为绕丹宁水解为 MBL 蛋白折叠以及其他金属酶的有效抑制剂的潜力提供了额外的证据，也许有助于绕丹宁​​的复杂生物效应。结果意味着任何使用绕丹宁（和相关支架）作为抑制剂的药物化学研究当然应该包括对其水解产物的测试。
• Structure–activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein–protein interaction inhibitors
  作者：Khuloud Takrouri、Ting Chen、Evangelos Papadopoulos、Rupam Sahoo、Eihab Kabha、Han Chen、Sonia Cantel、Gerhard Wagner、Jose A. Halperin、Bertal H. Aktas、Michael Chorev

  DOI：10.1016/j.ejmech.2014.03.034

  日期：2014.4

  Protein-protein interactions are critical for regulating the activity of translation initiation factors and multitude of other cellular process, and form the largest block of untapped albeit most challenging targets for drug development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl)hydrazono)-3-(2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening campaign of small molecule libraries as an inhibitor of translation initiation factors elF4E and eIF4G protein protein interaction; it inhibits translation initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl hydrazones have been designed and synthesized in order to delineate the structural latitude and improve its binding affinity to eIF4E, and increase its potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4-phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led to analogs with enhanced binding affinity and translation initiation inhibitory activities. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors
  作者：Daniel J. Burkett、Brittney N. Wyatt、Mallory Mews、Anson Bautista、Ryan Engel、Chris Dockendorff、William A. Donaldson、Martin St. Maurice

  DOI：10.1016/j.bmc.2019.07.027

  日期：2019.9

  5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.

  通过基于结构的药物设计项目（SBDD），发现了有效的丙酮酸羧化酶小分子抑制剂（PC）。制备了一系列α-酮酸（7）和α-羟基肉桂酸（8），并在两种测定中评估了其对PC的抑制作用。两种最有效的抑制剂是3,3'-（1,4-亚苯基）双[2-羟基-2-丙酸]（8u）和2-羟基-3-（喹啉-2-基）丙酸（8v））的IC 50值分别为3.0±1.0μM和4.3±1.5μM。化合物8v是相对于丙酮酸（K i = 0.74μM）和针对ATP的混合型抑制剂，表明它靶向PC的独特羧基转移酶（CT）域。此外，化合物8v不会显着抑制人碳酸酐酶II，基质金属蛋白酶-2，苹果酸脱氢酶或乳酸脱氢酶。
• 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.