(E)-3-(3,4-dichlorophenyl)-1-(4-(2-phenylacetyl)piperazin-1-yl)prop-2-en-1-one | 1599431-90-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3,4-dichlorophenyl)-1-(4-(2-phenylacetyl)piperazin-1-yl)prop-2-en-1-one
• 英文别名: (E)-3-(3,4-dichlorophenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one
• CAS: 1599431-90-9
• 化学式: C₂₁H₂₀Cl₂N₂O₂
• 分子量: 403.308
• InChiKey: WDZLLVLOVVTTEO-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(2-phenylacetyl)piperazine-1-carboxylate 在 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (E)-3-(3,4-dichlorophenyl)-1-(4-(2-phenylacetyl)piperazin-1-yl)prop-2-en-1-one
  参考文献：
  名称：

  Identification and Characterization of Small Molecule Modulators of the Epstein–Barr Virus-Induced Gene 2 (EBI2) Receptor

  摘要：

  Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) (Nature 2011, 475, 524; 519). EBI2 is highly expressed in immune cells (J. Biol. Chem. 2006, 281, 13199), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes (Nature 2010, 467, 460). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled 0 identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry. campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.

  DOI：

  10.1021/jm4019355

文献信息

• Identification and Characterization of Small Molecule Modulators of the Epstein–Barr Virus-Induced Gene 2 (EBI2) Receptor
  作者：Francois Gessier、Inga Preuss、Hong Yin、Mette M. Rosenkilde、Stephane Laurent、Ralf Endres、Yu A. Chen、Thomas H. Marsilje、Klaus Seuwen、Deborah G. Nguyen、Andreas W. Sailer

  DOI：10.1021/jm4019355

  日期：2014.4.24

  Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) (Nature 2011, 475, 524; 519). EBI2 is highly expressed in immune cells (J. Biol. Chem. 2006, 281, 13199), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes (Nature 2010, 467, 460). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled 0 identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry. campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.