ethyl 3-((3,5-dibromo-4-(3-isopropylphenoxy)phenyl)amino)-3-oxopropanoate

• 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: ethyl 3-((3,5-dibromo-4-(3-isopropylphenoxy)phenyl)amino)-3-oxopropanoate
• 英文别名: Ethyl 3-[3,5-dibromo-4-(3-propan-2-ylphenoxy)anilino]-3-oxopropanoate；ethyl 3-[3,5-dibromo-4-(3-propan-2-ylphenoxy)anilino]-3-oxopropanoate
• 化学式: C₂₀H₂₁Br₂NO₄
• 分子量: 499.199
• InChiKey: IAHWQZHOHQCIHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-异丙基苯酚 在 sodium dithionite 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲基叔丁基醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 3-((3,5-dibromo-4-(3-isopropylphenoxy)phenyl)amino)-3-oxopropanoate
  参考文献：
  名称：

  Rational Design of Potent and Selective Inhibitors of an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa

  摘要：

  The virulence factor cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is secreted by Pseudomonas aeruginosa and is the founding member of a distinct class of epoxide hydrolases (EHs) that triggers the catalysis-dependent degradation of the CFTR. We describe here the development of a series of potent and selective Cif inhibitors by structure-based drug design. Initial screening revealed la (KB2115), a thyroid hormone analog, as a lead compound with low micromolar potency. Structural requirements for potency were systematically probed, and interactions between Cif and la were characterized by X-ray crystallography. On the basis of these data, new compounds were designed to yield additional hydrogen bonding with residues of the Cif active site. From this effort, three compounds were identified that are 10-fold more potent toward Cif than our first-generation inhibitors and have no detectable thyroid hormone-like activity. These inhibitors will be useful tools to study the pathological role of Cif and have the potential for clinical application.

  DOI：

  10.1021/acs.jmedchem.6b00173

文献信息

• Rational Design of Potent and Selective Inhibitors of an Epoxide Hydrolase Virulence Factor from <i>Pseudomonas aeruginosa</i>
  作者：Seiya Kitamura、Kelli L. Hvorecny、Jun Niu、Bruce D. Hammock、Dean R. Madden、Christophe Morisseau

  DOI：10.1021/acs.jmedchem.6b00173

  日期：2016.5.26

  The virulence factor cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is secreted by Pseudomonas aeruginosa and is the founding member of a distinct class of epoxide hydrolases (EHs) that triggers the catalysis-dependent degradation of the CFTR. We describe here the development of a series of potent and selective Cif inhibitors by structure-based drug design. Initial screening revealed la (KB2115), a thyroid hormone analog, as a lead compound with low micromolar potency. Structural requirements for potency were systematically probed, and interactions between Cif and la were characterized by X-ray crystallography. On the basis of these data, new compounds were designed to yield additional hydrogen bonding with residues of the Cif active site. From this effort, three compounds were identified that are 10-fold more potent toward Cif than our first-generation inhibitors and have no detectable thyroid hormone-like activity. These inhibitors will be useful tools to study the pathological role of Cif and have the potential for clinical application.