rac-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[4-(3-methyl-5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-methanone | 1229628-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: rac-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[4-(3-methyl-5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-methanone
• 英文别名: [5-Methylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)phenyl]-[4-[3-methyl-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methanone
• CAS: 1229628-01-6
• 化学式: C₂₂H₂₃F₆N₃O₄S
• 分子量: 539.499
• InChiKey: XCAKSQRXTDCBOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  88.2
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  rac-[4-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone 、 三甲基铝 在 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 68.0h， 以46%的产率得到rac-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[4-(3-methyl-5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-methanone
  参考文献：
  名称：

  Selective GlyT1 Inhibitors: Discovery of [4-(3-Fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a Promising Novel Medicine To Treat Schizophrenia

  摘要：

  The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.

  DOI：

  10.1021/jm100210p