N-[3-(trifluoromethyl)phenyl]-2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]acetamide monohydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[3-(trifluoromethyl)phenyl]-2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]acetamide monohydrochloride
• 英文别名: N-(3-Trifluoromethyl-phenyl)-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-acetamide；N-[3-(trifluoromethyl)phenyl]-2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]acetamide;hydrochloride
• 化学式: C₂₀H₁₉F₆N₃O*ClH
• 分子量: 467.842
• InChiKey: KDKQQEFJTXVJSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.91
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  35.6
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(氯乙酰)-3-(三氟甲基) 苯胺 、 1-(3-三氟甲基苯基)哌嗪 在 potassium carbonate 、 potassium iodide 、 盐酸 作用下， 以 丙酮 、 乙醇 为溶剂， 反应 24.0h， 生成 N-[3-(trifluoromethyl)phenyl]-2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]acetamide monohydrochloride
  参考文献：
  名称：

  Synthesis and anticonvulsant activity of new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives

  摘要：

  Twenty-two new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives have been synthesized and evaluated for their anticonvulsant activity in animal models of epilepsy. These molecules have been designed as analogs of previously obtained anticonvulsant active pyrrolidine-2,5-diones in which heterocyclic imide ring has been changed into chain amide bound. The final compounds were synthesized in the alkylation reaction of the corresponding amines with the previously obtained alkylating reagents 2-chloro-1-(3-chlorophenyl)ethanone (1) or 2-chloro-1-[3-(trifluoromethyl)phenyl]ethanone (2). Initial anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole screens in mice and/or rats. Several compounds were tested additionally in the psychomotor seizures (6-Hz model). The acute neurological toxicity was determined applying the rotarod test. The results of pharmacological studies showed activity exclusively in the MES seizures especially for 3-(trifluoromethyl)anilide derivatives, whereas majority of 3-chloroanilide analogs were inactive. It should be emphasize that several molecules showed also activity in the 6-Hz screen which is an animal model of human partial and therapy-resistant epilepsy. In the in vitro studies, the most potent derivative 20 was observed as moderate binder to the neuronal voltage-sensitive sodium channels (site 2). The SAR studies for anticonvulsant activity confirmed the crucial role of pyrrolidine-2,5-dione core fragment for anticonvulsant activity.

  DOI：

  10.1007/s00044-015-1360-6

文献信息

• Synthesis and anticonvulsant activity of new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives
  作者：Krzysztof Kamiński、Beata Wiklik、Jolanta Obniska

  DOI：10.1007/s00044-015-1360-6

  日期：2015.7

  Twenty-two new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives have been synthesized and evaluated for their anticonvulsant activity in animal models of epilepsy. These molecules have been designed as analogs of previously obtained anticonvulsant active pyrrolidine-2,5-diones in which heterocyclic imide ring has been changed into chain amide bound. The final compounds were synthesized in the alkylation reaction of the corresponding amines with the previously obtained alkylating reagents 2-chloro-1-(3-chlorophenyl)ethanone (1) or 2-chloro-1-[3-(trifluoromethyl)phenyl]ethanone (2). Initial anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole screens in mice and/or rats. Several compounds were tested additionally in the psychomotor seizures (6-Hz model). The acute neurological toxicity was determined applying the rotarod test. The results of pharmacological studies showed activity exclusively in the MES seizures especially for 3-(trifluoromethyl)anilide derivatives, whereas majority of 3-chloroanilide analogs were inactive. It should be emphasize that several molecules showed also activity in the 6-Hz screen which is an animal model of human partial and therapy-resistant epilepsy. In the in vitro studies, the most potent derivative 20 was observed as moderate binder to the neuronal voltage-sensitive sodium channels (site 2). The SAR studies for anticonvulsant activity confirmed the crucial role of pyrrolidine-2,5-dione core fragment for anticonvulsant activity.