4-{3-[(benzyloxy)methyl]-2-methylphenyl}-3-(biphenyl-4-yl)-5-ethyl-4H-1,2,4-triazole | 1446690-52-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-{3-[(benzyloxy)methyl]-2-methylphenyl}-3-(biphenyl-4-yl)-5-ethyl-4H-1,2,4-triazole
• 英文别名: 3-Ethyl-4-[2-methyl-3-(phenylmethoxymethyl)phenyl]-5-(4-phenylphenyl)-1,2,4-triazole；3-ethyl-4-[2-methyl-3-(phenylmethoxymethyl)phenyl]-5-(4-phenylphenyl)-1,2,4-triazole
• CAS: 1446690-52-3
• 化学式: C₃₁H₂₉N₃O
• 分子量: 459.591
• InChiKey: HTPJVGPBDLCAKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-{3-[(benzyloxy)methyl]-2-methylphenyl}-3-(biphenyl-4-yl)-5-ethyl-4H-1,2,4-triazole 在 氯化亚砜 、 sodium methylate 、 三氯化硼 作用下， 以 四氢呋喃 、 正庚烷 、 氯仿 为溶剂， 反应 5.5h， 生成 3-(biphenyl-4-yl)-5-ethyl-4-[3-(methoxymethyl)-2-methylphenyl]-4H-1,2,4-triazole
  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
• 作为产物：
  描述：

  3-[(benzyloxy)methyl]-2-methylaniline 、 2-(biphenyl-4-yl)-5-ethyl-1,3,4-oxadiazole 在 对甲苯磺酸 作用下， 反应 3.0h， 以90%的产率得到4-{3-[(benzyloxy)methyl]-2-methylphenyl}-3-(biphenyl-4-yl)-5-ethyl-4H-1,2,4-triazole
  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.