ethyl 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzoate
• 英文别名: Ethyl 4-[3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-5-methyl-1,2,4-triazol-1-yl]-2-methylbenzoate；ethyl 4-[3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-5-methyl-1,2,4-triazol-1-yl]-2-methylbenzoate
• 化学式: C₂₁H₁₉F₄N₃O₂
• 分子量: 421.394
• InChiKey: DSENEBNSURIVGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzoate 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以94%的产率得到4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzoic acid
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists

  摘要：

  G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzy1)-5-methyl-1H-1,2,4-triazol-1-y1)-2-methylbenzamide (4u; half maximal effective concentration (EC50) = 75 nM, maximal response (E-max) = 122%) starting from a high-throughput screening hit 3 (EC50 = 470 nM, E-max = 56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists. A structure-activity relationship study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole derivative 4u, which demonstrated excellent bioavailability in rats (F = 53.8%). Oral administration of 4u (10 mg/kg) significantly suppressed methamphetamine-induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug discovery research of GPR52 agonists. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.064
• 作为产物：
  描述：

  4-氟-2-甲基苯甲酸乙酯 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 9.0h， 生成 ethyl 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzoate
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists

  摘要：

  G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzy1)-5-methyl-1H-1,2,4-triazol-1-y1)-2-methylbenzamide (4u; half maximal effective concentration (EC50) = 75 nM, maximal response (E-max) = 122%) starting from a high-throughput screening hit 3 (EC50 = 470 nM, E-max = 56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists. A structure-activity relationship study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole derivative 4u, which demonstrated excellent bioavailability in rats (F = 53.8%). Oral administration of 4u (10 mg/kg) significantly suppressed methamphetamine-induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug discovery research of GPR52 agonists. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.064