(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

文献信息

• SAR exploration at the C-3 position of tetrahydro-β-carboline sstr3 antagonists
  作者：Shuwen He、Peter H. Dobbelaar、Liangqin Guo、Zhixiong Ye、Jian Liu、Tianying Jian、Quang Truong、Shrenik K. Shah、Wu Du、Hongbo Qi、Raman K. Bakshi、Qingmei Hong、James D. Dellureficio、Edward Sherer、Alexander Pasternak、Zhe Feng、Mikhail Reibarkh、Melissa Lin、Koppara Samuel、Vijay B. Reddy、Stan Mitelman、Sharon X. Tong、Gary G. Chicchi、Kwei-Lan Tsao、Dorina Trusca、Margaret Wu、Qing Shao、Maria E. Trujillo、Guillermo Fernandez、Donald Nelson、Patricia Bunting、Janet Kerr、Patrick Fitzgerald、Pierre Morissette、Sylvia Volksdorf、George J. Eiermann、Cai Li、Bei B. Zhang、Andrew D. Howard、Yun-Ping Zhou、Ravi P. Nargund、William K. Hagmann

  DOI：10.1016/j.bmcl.2016.02.022

  日期：2016.3

  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.