N-[3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-4-(4-fluorophenethyl)piperazine-1-carboxamide trifluoroacetic acid | 1235992-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-4-(4-fluorophenethyl)piperazine-1-carboxamide trifluoroacetic acid
• 英文别名: N-[3-(4-chloro-2-methylpyrazol-3-yl)-4-methoxyphenyl]-4-[2-(4-fluorophenyl)ethyl]piperazine-1-carboxamide;2,2,2-trifluoroacetic acid
• CAS: 1235992-73-0
• 化学式: C₂HF₃O₂*C₂₄H₂₇ClFN₅O₂
• 分子量: 585.986
• InChiKey: XGSNOYNEXBONKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.91
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-[3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-4-(4-fluorophenethyl)piperazine-1-carboxamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 以441 mg的产率得到N-[3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-4-(4-fluorophenethyl)piperazine-1-carboxamide trifluoroacetic acid
  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