(1S,2R,8aS)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-1-(4-fluorophenyl)-7-(2-methoxypyridin-4-yl)-2,3,8,8a-tetrahydroindolizin-5(1H)-one | 1227071-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (1S,2R,8aS)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-1-(4-fluorophenyl)-7-(2-methoxypyridin-4-yl)-2,3,8,8a-tetrahydroindolizin-5(1H)-one
• CAS: 1227071-33-1
• 化学式: C₃₀H₂₅F₇N₂O₃
• 分子量: 594.529
• InChiKey: RPEJUMUSKMYYSP-CJJOHGCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  42.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.66
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2-甲氧基吡啶-4-硼酸 、 (1S,2R,8aS)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-1-(4-fluorophenyl)-5-oxo-1,2,3,5,8,8a-hexahydroindolizin-7-yl trifluoromethanesulfonate 在 四(三苯基膦)钯 作用下， 以 水 、 甲苯 为溶剂， 反应 18.0h， 生成 (1S,2R,8aS)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-1-(4-fluorophenyl)-7-(2-methoxypyridin-4-yl)-2,3,8,8a-tetrahydroindolizin-5(1H)-one
  参考文献：
  名称：

  Tetrahydroindolizinone NK1 antagonists

  摘要：

  A new class of potent NK1 receptor antagonists with a tetrahydroindolizinone core has been identified. This series of compounds demonstrated improved functional activities as compared to previously identified 5,5-fused pyrrolidine lead structures. SAR at the 7-position of the tetrahydroindolizinone core is discussed in detail. A number of compounds displayed high NK1 receptor occupancy at both 1 h and 24 h in a gerbil foot tapping model. Compound 40 has high NK1 binding affinity, good selectivity for other NK receptors and promising in vivo properties. It also has clean P-450 inhibition and hPXR induction profiles. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.120