1-[5-ethyl-4-(2-fluorophenyl)-4H-[1,2,4]triazol-3-yl]-4-phenylpiperidine | 374887-14-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-[5-ethyl-4-(2-fluorophenyl)-4H-[1,2,4]triazol-3-yl]-4-phenylpiperidine
• 英文别名: 1-[5-Ethyl-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]-4-phenylpiperidine；1-[5-ethyl-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]-4-phenylpiperidine
• CAS: 374887-14-6
• 化学式: C₂₁H₂₃FN₄
• 分子量: 350.439
• InChiKey: YVBNCDNALNHERK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-ethyl-4-(2-fluorophenyl)-4H-1,2,4-triazole 在 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 作用下， 以 四氯化碳 为溶剂， 反应 4.5h， 生成 1-[5-ethyl-4-(2-fluorophenyl)-4H-[1,2,4]triazol-3-yl]-4-phenylpiperidine
  参考文献：
  名称：

  Atropisomeric 4-Phenyl-4H-1,2,4-triazoles as Selective Glycine Transporter 1 Inhibitors

  摘要：

  We report on the optimization of 4H-1,2,4-triazole derivatives to increase their activity and selectivity as glycine transporter 1 (GlyT1) inhibitors. Structure-activity relationship exploration resulted in the identification of a 3-[3-ethyl-5-(6-phenylpyridin-3-yl)-4H-1,2,4-triazol-4-yl]-2-methyl-benzonitrile (14u) compound with markedly higher selectivity for GlyT1. Physiochemical studies revealed that 14u exists as a stable pair of atropisomers under physiological conditions. We successfully separated the atropisomers to obtain active enantiomer (R)-14u, which displayed favorable pharmacokinetic properties, as well as positive results in the mice Y-maze test.

  DOI：

  10.1021/jm400383w

文献信息

• Atropisomeric 4-Phenyl-4<i>H</i>-1,2,4-triazoles as Selective Glycine Transporter 1 Inhibitors
  作者：Takashi Sugane、Takahiko Tobe、Wataru Hamaguchi、Itsuro Shimada、Kyoichi Maeno、Junji Miyata、Takeshi Suzuki、Tetsuya Kimizuka、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1021/jm400383w

  日期：2013.7.25

  We report on the optimization of 4H-1,2,4-triazole derivatives to increase their activity and selectivity as glycine transporter 1 (GlyT1) inhibitors. Structure-activity relationship exploration resulted in the identification of a 3-[3-ethyl-5-(6-phenylpyridin-3-yl)-4H-1,2,4-triazol-4-yl]-2-methyl-benzonitrile (14u) compound with markedly higher selectivity for GlyT1. Physiochemical studies revealed that 14u exists as a stable pair of atropisomers under physiological conditions. We successfully separated the atropisomers to obtain active enantiomer (R)-14u, which displayed favorable pharmacokinetic properties, as well as positive results in the mice Y-maze test.