4-(4-amino-2,6-dichlorophenoxy)-2-isopropylphenol | 355129-25-8

• 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: 4-(4-amino-2,6-dichlorophenoxy)-2-isopropylphenol
• 英文别名: 4-(4-Amino-2,6-dichlorophenoxy)-2-propan-2-ylphenol
• CAS: 355129-25-8
• 化学式: C₁₅H₁₅Cl₂NO₂
• 分子量: 312.196
• InChiKey: BDAOGDICUULGML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-amino-2,6-dichlorophenoxy)-2-isopropylphenol 、 方酸 以 水 为溶剂， 以41%的产率得到3-(3,5-Dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenylamino)-4-hydroxycyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  设计和合成新型3-羟基-环丁-3-烯-1,2-二酮衍生物，作为甲状腺激素受体β（TR-β）选择性配体。

  摘要：

  报道了新型3-羟基-环丁-3-烯-1,2-二酮衍生物的设计和合成，并在甲状腺荧光素酶受体测定中评估了它们的体外甲状腺激素受体选择性。3- [3,5-二氯-4-（4-羟基-3-异丙基苯氧基）-苯基氨基] -4-羟基-环丁-3-烯-1,2-二酮21对甲状腺激素受体β表现出选择性。

  DOI：

  10.1016/j.bmcl.2008.06.038
• 作为产物：
  描述：

  2-异丙基苯甲醚 在 sodium dithionite 、 双氧水 、 三溴化硼 、 对甲苯磺酸 、 sodium hydrogensulfite 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(4-amino-2,6-dichlorophenoxy)-2-isopropylphenol
  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.
• Design and synthesis of novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives as thyroid hormone receptor β (TR-β) selective ligands
  作者：Saurin Raval、Preeti Raval、Debdutta Bandyopadhyay、Krunal Soni、Digambar Yevale、Digvijay Jogiya、Honey Modi、Amit Joharapurkar、Neha Gandhi、Mukul R. Jain、Pankaj R. Patel

  DOI：10.1016/j.bmcl.2008.06.038

  日期：2008.7

  Design and synthesis of a novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives are reported and their in vitro thyroid hormone receptor selectivity has been evaluated in the thyroid luciferase receptor assay. The 3-[3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)-phenylamino]-4-hydroxy-cyclobut- 3-ene-1,2-dione 21 has shown selectivity towards thyroid hormone receptor beta.

  报道了新型3-羟基-环丁-3-烯-1,2-二酮衍生物的设计和合成，并在甲状腺荧光素酶受体测定中评估了它们的体外甲状腺激素受体选择性。3- [3,5-二氯-4-（4-羟基-3-异丙基苯氧基）-苯基氨基] -4-羟基-环丁-3-烯-1,2-二酮21对甲状腺激素受体β表现出选择性。