4-(4-amino-2,6-dichlorophenoxy)phenol | 290351-11-0

• 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)phenol
• CAS: 290351-11-0
• 化学式: C₁₂H₉Cl₂NO₂
• 分子量: 270.115
• InChiKey: MTXYBMDQHZRRDK-UHFFFAOYSA-N

物化性质

• 沸点：
  408.6±45.0 °C(predicted)
• 密度：
  1.462±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 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：
  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)phenol 、 间甲氧基苯甲酰氯 以 四氢呋喃 为溶剂， 反应 0.83h， 生成 N-[3,5-dichloro-4-(4-hydroxyphenoxy)phenyl]-3-methoxybenzamide
  参考文献：
  名称：

  新型（苯甲酰氨基苯氧基）苯酚衍生物作为抗前列腺癌药物的构效关系

  摘要：

  雄激素受体（AR）是属于核受体超家族的配体诱导转录因子，并且是用于开发治疗前列腺癌的药物的靶分子。但是，临床应用中的AR拮抗剂，例如氟他胺（3a）和比卡鲁胺（4），在经过数年的激素治疗后会产生耐药性，这主要是由于AR突变引起的。因此，尽管已经开发了一些新一代的AR拮抗剂，但是仍需要新型类型的AR拮抗剂来治疗耐药性前列腺癌。我们之前报道了一种新颖的（苯甲酰基氨基苯氧基）苯酚衍生物10a，在结构上与传统的AR拮抗剂不同。在这里，我们系统地研究了（苯甲酰氨基苯氧基）苯酚衍生物对前列腺癌细胞增殖抑制活性的结构-活性关系。我们发现4- [4-（苯甲酰氨基）苯氧基]苯酚骨架对抗前列腺癌活性很重要。在中心苯环（B环）的2位引入一个小的取代基可以提高活性。在合成的化合物中，19a和19b对几种雄激素依赖性细胞系SC-3（野生型AR），LNCaP（T877A AR）和22Rv1（H874Y AR）的二氢睾丸

  DOI：

  10.1016/j.bmc.2018.09.008
• 作为产物：
  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

文献信息

• 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。
• 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。
• 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.