2-(3-bromo-4-(methylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol | 1395060-13-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(3-bromo-4-(methylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol
• 英文别名: 2-[3-Bromo-4-(methylamino)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol；2-[3-bromo-4-(methylamino)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
• CAS: 1395060-13-5
• 化学式: C₁₀H₈BrF₆NO
• 分子量: 352.074
• InChiKey: FXIUREPUMFJULC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-bromo-4-(methylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol 在 四(三苯基膦)钯 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 N-[2-ethenyl-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-iodo-N-methylbenzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Transrepression-Selective Liver X Receptor (LXR) Ligands with 5,11-Dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one Skeleton

  摘要：

  To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR ligand-binding domain led to a series of compounds, of which almost all exhibited transrepressional activity at 1 or 10 mu M but showed no transactivational activity even at 30 mu M. Among the compounds obtained, 18 and 22 were confirmed to have LXR-dependent transrepressional activity by using peritoneal macrophages from wild-type and LXR-null mice. A newly developed fluorescence polarization assay indicated that they bind directly to LXR alpha. Next, further structural modification was performed with the guidance of docking simulations with LXR alpha, focusing on enhancing the binding of the ligands with LXR alpha through the introduction of substituents or heteroatom(s). Among the compounds synthesized, compound 48, bearing a hydroxyl group, showed potent, selective, and dose-dependent transrepressional activity.

  DOI：

  10.1021/jm3002394
• 作为产物：
  描述：

  1,1,1,3,3,3-六氟-2-(4-(甲基氨基)苯基)-2-丙醇 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 2-(3-bromo-4-(methylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Transrepression-Selective Liver X Receptor (LXR) Ligands with 5,11-Dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one Skeleton

  摘要：

  To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR ligand-binding domain led to a series of compounds, of which almost all exhibited transrepressional activity at 1 or 10 mu M but showed no transactivational activity even at 30 mu M. Among the compounds obtained, 18 and 22 were confirmed to have LXR-dependent transrepressional activity by using peritoneal macrophages from wild-type and LXR-null mice. A newly developed fluorescence polarization assay indicated that they bind directly to LXR alpha. Next, further structural modification was performed with the guidance of docking simulations with LXR alpha, focusing on enhancing the binding of the ligands with LXR alpha through the introduction of substituents or heteroatom(s). Among the compounds synthesized, compound 48, bearing a hydroxyl group, showed potent, selective, and dose-dependent transrepressional activity.

  DOI：

  10.1021/jm3002394

文献信息

• Copper(II)‐Catalysed Aerobic Oxidative Coupling of Arylamines with Hexafluoroisopropanol: An Alternative Methodology for Constructing Fluorinated Compounds
  作者：Liangying Wu、Yang Song、Zhanchong Li、Jiabao Guo、Xiaoquan Yao

  DOI：10.1002/adsc.202001048

  日期：2021.1.5

  The selective functionalisation of arylamine derivatives with hexafluoroisopropanol through copper(II)‐catalysed aerobic oxidative coupling was developed to generate various fluoroalkylated arylamines under mild conditions. This method has a wide substrate scope with excellent functional group tolerance and provides the fluorinated products in good to excellent yields. Furthermore, preliminary studies

  开发了在铜（II）催化的需氧氧化偶联作用下，六氟异丙醇对芳胺衍生物的选择性官能化反应，可在温和条件下生成各种氟代烷基化芳基胺。该方法具有广泛的底物范围，具有优异的官能团耐受性，并且以良好至优异的产率提供了氟化产物。此外，初步研究表明该反应是通过自由基机理发生的。该协议使用大气中的O 2作为氧化剂，为构建氟化化合物提供了另一种绿色途径。
• Design, Synthesis, and Biological Evaluation of Novel Transrepression-Selective Liver X Receptor (LXR) Ligands with 5,11-Dihydro-5-methyl-11-methylene-6<i>H</i>-dibenz[<i>b</i>,<i>e</i>]azepin-6-one Skeleton
  作者：Atsushi Aoyama、Kaori Endo-Umeda、Kenji Kishida、Kenji Ohgane、Tomomi Noguchi-Yachide、Hiroshi Aoyama、Minoru Ishikawa、Hiroyuki Miyachi、Makoto Makishima、Yuichi Hashimoto

  DOI：10.1021/jm3002394

  日期：2012.9.13

  To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR ligand-binding domain led to a series of compounds, of which almost all exhibited transrepressional activity at 1 or 10 mu M but showed no transactivational activity even at 30 mu M. Among the compounds obtained, 18 and 22 were confirmed to have LXR-dependent transrepressional activity by using peritoneal macrophages from wild-type and LXR-null mice. A newly developed fluorescence polarization assay indicated that they bind directly to LXR alpha. Next, further structural modification was performed with the guidance of docking simulations with LXR alpha, focusing on enhancing the binding of the ligands with LXR alpha through the introduction of substituents or heteroatom(s). Among the compounds synthesized, compound 48, bearing a hydroxyl group, showed potent, selective, and dose-dependent transrepressional activity.