1-(4-fluorophenyl)-2-[4-(5-methyl-2-phenyl-2H-pyrazole-3-carbonyl)piperazin-1-yl]ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-2-[4-(5-methyl-2-phenyl-2H-pyrazole-3-carbonyl)piperazin-1-yl]ethanone
• 英文别名: 1-(4-fluorophenyl)-2-[4-(5-methyl-1-phenylpyrazole-3-carbonyl)piperazin-1-yl]ethanone
• 化学式: C₂₃H₂₃FN₄O₂
• 分子量: 406.46
• InChiKey: KDGPFASOCRGLCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone hydrochloride 、 5-甲基-1-苯基吡唑-3-羧酸 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以52%的产率得到1-(4-fluorophenyl)-2-[4-(5-methyl-2-phenyl-2H-pyrazole-3-carbonyl)piperazin-1-yl]ethanone
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of Phenethylpiperazine Amides: Selective 5-Hydroxytryptamine_2A Receptor Antagonists for the Treatment of Insomnia

  摘要：

  Recent developments in sleep research suggest that antagonism of the serotonin 5-HT2A receptor may improve sleep maintenance insomnia. We herein report the discovery of a series of potent and selective serotonin 5-HT2A receptor antagonists based on a phenethylpiperazine amide core structure. When tested in a rat sleep pharmacology model, these compounds increased both sleep consolidation and deep sleep. Within this series of compounds, an improvement in the metabolic stability of early leads was achieved by introducing a carbonyl group into the phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5-HT2A receptor binding affinity, high selectivity over the 5-HT2C receptor, favorable CNS partitioning, and good pharmacokinetic and early safety profiles. In vivo, these two compounds showed dose-dependent, statistically significant improvements on deep sleep (delta power) and sleep consolidation at doses as low as 0.1 mg/kg.

  DOI：

  10.1021/jm100479q

文献信息

• Synthesis and in Vivo Evaluation of Phenethylpiperazine Amides: Selective 5-Hydroxytryptamine_2A Receptor Antagonists for the Treatment of Insomnia
  作者：Yifeng Xiong、Brett Ullman、Jin-Sun Karoline Choi、Martin Cherrier、Sonja Strah-Pleynet、Marc Decaire、Peter I. Dosa、Konrad Feichtinger、Bradley R. Teegarden、John M. Frazer、Woo H. Yoon、Yun Shan、Kevin Whelan、Erin K. Hauser、Andrew J. Grottick、Graeme Semple、Hussien Al-Shamma

  DOI：10.1021/jm100479q

  日期：2010.8.12

  Recent developments in sleep research suggest that antagonism of the serotonin 5-HT2A receptor may improve sleep maintenance insomnia. We herein report the discovery of a series of potent and selective serotonin 5-HT2A receptor antagonists based on a phenethylpiperazine amide core structure. When tested in a rat sleep pharmacology model, these compounds increased both sleep consolidation and deep sleep. Within this series of compounds, an improvement in the metabolic stability of early leads was achieved by introducing a carbonyl group into the phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5-HT2A receptor binding affinity, high selectivity over the 5-HT2C receptor, favorable CNS partitioning, and good pharmacokinetic and early safety profiles. In vivo, these two compounds showed dose-dependent, statistically significant improvements on deep sleep (delta power) and sleep consolidation at doses as low as 0.1 mg/kg.