N-[4-(5-carbamoyl-2-chlorophenyl)-2-(2,2,2-trifluoroethoxy)phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide | 1532509-33-3

• 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: N-[4-(5-carbamoyl-2-chlorophenyl)-2-(2,2,2-trifluoroethoxy)phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
• CAS: 1532509-33-3
• 化学式: C₂₃H₁₆Cl₂F₄N₂O₃
• 分子量: 518.267
• InChiKey: NVMQCZDBIJGVBJ-FIBGUPNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.63
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  4-Bromo-1-nitro-2-(2,2,2-trifluoroethoxy)-benzene 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 铁粉 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N-[4-(5-carbamoyl-2-chlorophenyl)-2-(2,2,2-trifluoroethoxy)phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
  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