(1R,3R)-3-[3-(4-fluorophenyl)-1H-1,2,4-triazol-5-yl]-1-(oxan-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole | 1225019-11-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1R,3R)-3-[3-(4-fluorophenyl)-1H-1,2,4-triazol-5-yl]-1-(oxan-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• CAS: 1225019-11-3
• 化学式: C₂₄H₂₄FN₅O
• 分子量: 417.486
• InChiKey: RPYGDVQBRLSKDU-NHCUHLMSSA-N

物化性质

• 沸点：
  686.4±65.0 °C(predicted)
• 密度：
  1.328±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氟硫代苄胺 以 乙醇 、 丙酮 为溶剂， 反应 80.0h， 生成 (1R,3R)-3-[3-(4-fluorophenyl)-1H-1,2,4-triazol-5-yl]-1-(oxan-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  参考文献：
  名称：

  SAR exploration at the C-3 position of tetrahydro-β-carboline sstr3 antagonists

  摘要：

  MK-4256, a tetrahydro-beta-carboline sstr3 antagonist, was discontinued due to a cardiovascular (CV) adverse effect observed in dogs. Additional investigations revealed that the CV liability (QTc prolongation) was caused by the hERG off-target activity of MK-4256 and was not due to sstr3 antagonism. In this Letter, we describe our extensive SAR effort at the C3 position of the tetrahydro-beta-carboline structure. This effort resulted in identification of 5-fluoro-pyridin-2-yl as the optimal substituent on the imidazole ring to balance sstr3 activity and the hERG off-target liability. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.022