4-(2,6-dichloro-4-nitrophenoxy)phenol

• 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-(2,6-dichloro-4-nitrophenoxy)phenol
• 化学式: C₁₂H₇Cl₂NO₄
• 分子量: 300.098
• InChiKey: LQTKNGHYIVZBRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2,6-dichloro-4-nitrophenoxy)phenol 在 sodium dithionite 作用下， 以 四氢呋喃 、 水 为溶剂， 以100%的产率得到4-(4-amino-2,6-dichlorophenoxy)phenol
  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
• 作为产物：
  描述：

  1-(2,6-二氯-4-硝基-苯氧基)-4-甲氧基-苯 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以63%的产率得到4-(2,6-dichloro-4-nitrophenoxy)phenol
  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

• Oxamic acids and derivatives as thyroid receptor ligands
  申请人：——

  公开号：US20030114521A1

  公开（公告）日：2003-06-19

  The present invention provides novel compounds of the Formula 1 and prodrugs thereof, geometric and optical isomers thereof, and pharmaceutically acceptable salts of such compounds, prodrugs and isomers, wherein R 1 —R 8 and W are as described herein. Pharmaceutical compositions containing such compounds, prodrugs, isomers or pharmaceutically acceptable salts thereof, and methods, pharmaceutical compositions and kits for treating obesity, hyperlipidemia, glaucoma, cardiac arrhythmia, skin disorders, thyroid disease, hypothyroidism and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, hypercholesteremia, depression and osteoporosis are also provided.

  本发明提供了式1的新化合物及其前药、几何和光学异构体以及这些化合物、前药和异构体的药学上可接受的盐，其中R1-R8和W如本文所述。还提供了含有这些化合物、前药、异构体或其药学上可接受的盐的药物组合物，以及用于治疗肥胖症、高脂血症、青光眼、心律失常、皮肤疾病、甲状腺疾病、甲状腺功能减退症以及相关的疾病和疾病，如糖尿病、动脉硬化、高血压、冠心病、高胆固醇血症、抑郁症和骨质疏松症的方法、药物组合物和工具包。
• Design, synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives
  作者：Ji-Chun Yang、Miao Li、Qiao Wu、Chang-Ling Liu、Xiu-Hui Chang

  DOI：10.1016/j.bmc.2015.09.030

  日期：2016.2

  Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by H-1 NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25 mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75-150 g a. i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75 g a. i./ha was equivalent to pyridalyl at 105 g a.i./ha. (C) 2015 Elsevier Ltd. All rights reserved.
• OXAMIC ACIDS AND DERIVATIVES AS THYROID RECEPTOR LIGANDS
  申请人：Pfizer Products Inc.

  公开号：EP1157001A1

  公开（公告）日：2001-11-28
• US6326398B1
  申请人：——

  公开号：US6326398B1

  公开（公告）日：2001-12-04
• [EN] OXAMIC ACIDS AND DERIVATIVES AS THYROID RECEPTOR LIGANDS<br/>[FR] ACIDES OXAMIQUES ET DERIVES UTILISES EN TANT QUE LIGANDS DU RECEPTEUR DES HORMONES THYROIDIENNES
  申请人：PFIZER PROD INC

  公开号：WO2000051971A1

  公开（公告）日：2000-09-08

  The present invention provides novel compounds of Formula (I) and prodrugs thereof, geometric and optical isomers thereof, and pharmaceutically acceptable salts of such compounds, prodrugs and isomers, wherein R1 - R8 and W are as described herein. Pharmaceutical compositions containing such compounds, prodrugs, isomers or pharmaceutically acceptable salts thereof, and methods, pharmaceutical compositions and kits for treating obesity, hyperlipidemia, glaucoma, cardiac arrythmia, skin disorders, thyroid disease, hypothyroidism and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, hypercholesteremia, depression and osteoporosis are also provided.