1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene | 258820-25-6

• 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: 1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene
• 英文别名: 2,6-dibromo-3'-isopropyl-4'-methoxy-4-nitrodiphenyl ether；4-(2,6-dibromo-4-nitrophenoxy)-2-isopropylanisole；1,3-dibromo-2-(4-methoxy-3-propan-2-ylphenoxy)-5-nitrobenzene
• CAS: 258820-25-6
• 化学式: C₁₆H₁₅Br₂NO₄
• 分子量: 445.107
• InChiKey: UCAICOGCYZTSIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  64.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene 以100的产率得到4-(2,6-dibromo-4-nitrophenoxy)-2-isopropylphenol
  参考文献：
  名称：

  Process for the preparation of aniline-derived thyroid receptor ligands

  摘要：

  提供了合成苯胺衍生物的过程，具体而言是具有甲状腺受体配体活性的某些苯胺衍生物。

  公开号：

  US20030157671A1
• 作为产物：
  描述：

  2-异丙基苯甲醚 在 双氧水 、 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 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene
  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
• 作为试剂：
  描述：

  2-异丙基-4-羟基苯甲醚 、 、 双(三甲基硅烷基)氨基钾 、 1,3-二溴-2-碘-5-硝基苯 、 碳酸氢钠 在 氮气 、 氯化钠 、 水 、 1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.75h， 生成 1,3-dibromo-2-(3-isopropyl-4-methoxyphenoxy)-5-nitrobenzene
  参考文献：
  名称：

  Process for the preparation of aniline-derived thyroid receptor ligands

  摘要：

  提供了合成苯胺衍生物的过程，具体而言是具有甲状腺受体配体活性的某些苯胺衍生物。

  公开号：

  US20050054873A1

文献信息

• Synthesis and Structure-Activity Relationships of Oxamic Acid and Acetic Acid Derivatives Related to L-Thyronine
  作者：Naokata Yokoyama、Gordon N. Walker、Alan J. Main、James L. Stanton、Michael M. Morrissey、Charles Boehm、Allan Engle、Alan D. Neubert、Jong M. Wasvary

  DOI：10.1021/jm00004a015

  日期：1995.2

  Aryloxamic acids 7 and 23, (arylamino)acetic acids 29, arylpropionic acids 33, arylthioacetic acids 37, and (aryloxy)acetic acid 41 related to L-triiodothyronine (L-T3) were prepared and tested in vitro for binding to the rat liver nuclear L-T3 receptor and the rat membrane L-T3 receptor. The structure-activity relationships for these compounds are described, with 7f, 23a, 29c, 33a, 37b, and 41 showing

  制备了与L-三碘甲甲状腺素（L-T3）有关的芳基草酸7和23，（芳基氨基）乙酸29，芳基丙酸33，芳基硫代乙酸37和（芳氧基）乙酸41并在体外测试了与大鼠肝脏的结合核L-T3受体和大鼠膜L-T3受体。描述了这些化合物的构效关系，其中7f，23a，29c，33a，37b和41对核受体显示出出色的效价（IC50分别为0.19、0.16、1.1、0.11、3.5和0.10 nM）。并显着降低了对膜受体的结合亲和力（IC50> 5 microM）。这些化合物中的某些，尤其是草酰胺酸系列7和23，对甲基取代的衍生物（例如7f和23a）表现出空前的效价。化合物7f和23a在具有ED50'的大鼠中显示出良好的降脂作用
• Novel Phosphinic Acid-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20090028925A1

  公开（公告）日：2009-01-29

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有磷酸基T3拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟
• Glucocorticoid and thyroid hormone receptor ligands for the treatment of metabolic disorders
  申请人：Karo Bio AB

  公开号：US06492424B1

  公开（公告）日：2002-12-10

  Novel glucocorticoid and thyroid receptor ligands as provided which have the general formula (I): in which R1 is an aliphatic hydrocarbon, an aromatic hydrocarbon, carboxylic acid or ester thereof, alkenyl carboxylic acid or ester thereof, hydroxy, halogen, or cyano, or a pharmaceutically acceptable salt thereof. R2 and R3 are the same or different, and are hydrogen, halogen, alkyl of 1 to 4 carbons, or cycloalkyl of 3 to 5 carbons, at least one of R2 and R3 being other than hydrogen. X is carbonyl or methylene. R4 is an aliphatic, aromatic or heteroaromatic. Y is hydroxyl, methoxy, amino, or alkyl amino. n is an integer from 0 to 4. A method for treating diseases associated with metabolism dysfunction or which are dependent on the expression of a glucocorticoid or thyroid receptor gene such as diabetes, hypercholesterolemia, or obesity using these compounds is also disclosed.

  提供了新型糖皮质激素和甲状腺受体配体，其具有一般式（I）：其中R1为脂肪烃、芳香烃、羧酸或其酯、烯基羧酸或其酯、羟基、卤素、或氰基，或其药用可接受的盐。R2和R3相同或不同，为氢、卤素、1至4碳的烷基，或3至5碳的环烷基，R2和R3中至少一个不是氢。X为羰基或亚甲基。R4为脂肪烃、芳香烃或杂环芳烃。Y为羟基、甲氧基、氨基或烷基氨基。n为0至4的整数。还公开了使用这些化合物治疗与代谢功能障碍有关或依赖于糖皮质激素或甲状腺受体基因表达的疾病的方法，例如糖尿病、高胆固醇血症或肥胖症。
• Novel Phosphorus-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20100081634A1

  公开（公告）日：2010-04-01

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有膦酸的T3模拟物化合物及其单酯、立体异构体、药学上可接受的盐、共晶体和前药及其药学上可接受的盐和共晶体，以及它们的制备和用于预防和/或治疗代谢性疾病，如肥胖症、NASH、高胆固醇血症和高脂血症，以及相关疾病，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征X和糖尿病的用途。
• Novel phosphorus-containing thyromimetics
  申请人：Erion D. Mark

  公开号：US20060046980A1

  公开（公告）日：2006-03-02

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有膦酸基的T3类似物化合物及其单酯体、立体异构体、药学上可接受的盐、共晶体和其前药物，以及前药物的药学上可接受的盐和共晶体，以及它们的制备和用于预防和/或治疗代谢性疾病，如肥胖症、NASH、高胆固醇血症和高脂血症，以及相关疾病，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征x和糖尿病。