4-bromo-2-(2,2,2-trifluoroethoxy)aniline | 1496808-60-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-bromo-2-(2,2,2-trifluoroethoxy)aniline
• CAS: 1496808-60-6
• 化学式: C₈H₇BrF₃NO
• 分子量: 270.049
• InChiKey: YCLMJAACWCUDOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  14.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.25
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-bromo-2-(2,2,2-trifluoroethoxy)aniline 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 水 、 sodium hydride 、 sodium carbonate 、 氯化铵 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 37.0h， 生成 N-(3-amino-3-oxopropyl)-6-chloro-4'-(2-chloro-6-fluoro-N-CD₃-benzamido)-3'-(2,2,2-trifhioroethoxy)-[1,1'-biphenyl]-3-carboxamide
  参考文献：
  名称：

  [EN] BIARYL-CONTAINING COMPOUNDS AS INVERSE AGONISTS OF ROR-GAMMA RECEPTORS
  [FR] COMPOSÉS CONTENANT BIARYLE COMME AGONISTES INVERSES DE RÉCEPTEURS ROR-GAMMA

  摘要：

  本发明涉及含有联苯基的ROR-gamma受体的逆激动剂。该发明还提供了包含这些含有联苯基的逆激动剂的药物组合物，以及使用这些逆激动剂调节ROR-gamma受体的方法。同时提供了使用含有联苯基的逆激动剂治疗ROR-gamma介导疾病的方法。

  公开号：

  WO2014008214A1
• 作为产物：
  描述：

  2-硝基-5-溴苯酚 在 铁粉 、 caesium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-bromo-2-(2,2,2-trifluoroethoxy)aniline
  参考文献：
  名称：

  Discovery of biaryl carboxylamides as potent RORγ inverse agonists

  摘要：

  ROR gamma t is a pivotal regulator of a pro-inflammatory gene expression program implicated in the pathology of several major human immune-mediated diseases. Evidence from mouse models demonstrates that genetic or pharmacological inhibition of ROR gamma activity can block the production of pathogenic cytokines, including IL-17, and convey therapeutic benefit. We have identified and developed a biaryl-carboxylamide series of ROR gamma inverse agonists via a structure based design approach. Co-crystal structures of compounds 16 and 48 supported the design approach and confirmed the key interactions with ROR gamma protein; the hydrogen bonding with His479 was key to the significant improvement in inverse agonist effect. The results have shown this is a class of potent and selective ROR gamma inverse agonists, with demonstrated oral bioavailability in rodents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.026

文献信息

• 2,4-DIAMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 MODULATORS
  申请人：Janssen Pharmaceutica NV

  公开号：US20180289706A1

  公开（公告）日：2018-10-11

  The present invention relates to 2,4-diaminopyrimidines and pharmaceutically acceptable salts thereof, purification methods for the same, pharmaceutical compositions containing them, methods of obtaining and using them for the treatment of disease states, disorders, and conditions mediated by the histamine H 4 receptor activity.

  本发明涉及2,4-二氨基嘧啶及其药用盐，其纯化方法，含有它们的药物组合物，以及用于治疗由组胺H4受体活性介导的疾病状态、紊乱和病况的获取和使用方法。
• 2,4-diaminopyrimidine derivatives as histamine H4 modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US10172856B2

  公开（公告）日：2019-01-08

  The present invention relates to 2,4-diaminopyrimidines and pharmaceutically acceptable salts thereof, purification methods for the same, pharmaceutical compositions containing them, methods of obtaining and using them for the treatment of disease states, disorders, and conditions mediated by the histamine H4 receptor activity.

  本发明涉及 2,4-二氨基嘧啶及其药学上可接受的盐、其纯化方法、含有它们的药物组合物、获得和使用它们治疗由组胺 H4 受体活性介导的疾病状态、紊乱和病症的方法。
• [EN] 2,4-DIAMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 MODULATORS<br/>[FR] DÉRIVÉS DE 2,4-DIAMINOPYRIMIDINE EN TANT QUE MODULATEURS DE L'HISTAMINE H4
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018187652A1

  公开（公告）日：2018-10-11

  The present invention relates to 2,4-diaminopyrimidines of formula (I) and pharmaceutically acceptable salts thereof, purification methods for the same, pharmaceutical compositions containing them, methods of obtaining and using them for the treatment of disease states, disorders, and conditions mediated by the histamine H4receptor activity.
• [EN] BIARYL-CONTAINING COMPOUNDS AS INVERSE AGONISTS OF ROR-GAMMA RECEPTORS<br/>[FR] COMPOSÉS CONTENANT BIARYLE COMME AGONISTES INVERSES DE RÉCEPTEURS ROR-GAMMA
  申请人：BIOGEN IDEC INC

  公开号：WO2014008214A1

  公开（公告）日：2014-01-09

  The present invention relates to biaryl-containing inverse agonists of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these biaryl- containing inverse agonists, and methods of modulating ROR-gamma receptors using these inverse agonists. Also provided are methods of using biaryl-containing inverse agonists to treat ROR-gamma mediated diseases.

  本发明涉及含有联苯基的ROR-gamma受体的逆激动剂。该发明还提供了包含这些含有联苯基的逆激动剂的药物组合物，以及使用这些逆激动剂调节ROR-gamma受体的方法。同时提供了使用含有联苯基的逆激动剂治疗ROR-gamma介导疾病的方法。
• Discovery of biaryl carboxylamides as potent RORγ inverse agonists
  作者：Jianhua Chao、Istvan Enyedy、Kurt Van Vloten、Douglas Marcotte、Kevin Guertin、Richard Hutchings、Noel Powell、Howard Jones、Tonika Bohnert、Chi-Chi Peng、Laura Silvian、Victor Sukbong Hong、Kevin Little、Daliya Banerjee、Liaomin Peng、Arthur Taveras、Joanne L. Viney、Jason Fontenot

  DOI：10.1016/j.bmcl.2015.05.026

  日期：2015.8

  ROR gamma t is a pivotal regulator of a pro-inflammatory gene expression program implicated in the pathology of several major human immune-mediated diseases. Evidence from mouse models demonstrates that genetic or pharmacological inhibition of ROR gamma activity can block the production of pathogenic cytokines, including IL-17, and convey therapeutic benefit. We have identified and developed a biaryl-carboxylamide series of ROR gamma inverse agonists via a structure based design approach. Co-crystal structures of compounds 16 and 48 supported the design approach and confirmed the key interactions with ROR gamma protein; the hydrogen bonding with His479 was key to the significant improvement in inverse agonist effect. The results have shown this is a class of potent and selective ROR gamma inverse agonists, with demonstrated oral bioavailability in rodents. (C) 2015 Elsevier Ltd. All rights reserved.