Cyclohexanecarboxylic acid [2-oxo-2-(3-trifluoromethyl-phenyl)-ethyl]-amide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Cyclohexanecarboxylic acid [2-oxo-2-(3-trifluoromethyl-phenyl)-ethyl]-amide
• 英文别名: N-[2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl]cyclohexanecarboxamide
• 化学式: C₁₆H₁₈F₃NO₂
• 分子量: 313.32
• InChiKey: AUQWLKIGBNPWQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cyclohexanecarboxylic acid [2-oxo-2-(3-trifluoromethyl-phenyl)-ethyl]-amide 在 ammonium acetate 、 溶剂黄146 作用下， 反应 16.0h， 生成 2-cyclohexyl-4-[3-(trifluoromethyl)phenyl]imidazole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Substituted 2-Cyclohexyl-4-phenyl-1H-imidazoles:  Potent and Selective Neuropeptide Y Y5-Receptor Antagonists

  摘要：

  Antagonizing the robust stimulation of food intake by neuropeptide Y represents a new potential therapeutic approach for the treatment of obesity. Earlier pharmacological studies have pointed to the Y1 and Y5 receptors as the most likely mediators of the NPY orexigenic response. In this paper, we describe a new series of small molecule Y5 antagonists derived from a 2,4diaryl-1H-imidazole lead. The main objectives of our structural optimization efforts were to produce novel and potent Y5 antagonists with an improved oral pharmacokinetic profile and less affinity for the hERG potassium channel compared to the lead 2,4-diarylimidazole structures. These goals were accomplished by replacement of the 2-aryl ring with a cyclohexyl ring and subsequent elaboration of the 4-position of the cyclohexyl ring with a variety of hydrophilic functionalities. The resulting compound, N-(2-hydroxy-tert-butyl)(4-{4-[3-(trifluoro-methyl)phenyl]imidazol-2-yl}cyclohexyl)carboxamide (20), displayed good potency at the Y5 receptor (K-i = 3 nM), while interactions at the hERG channel were essentially eliminated (6% inhibition at a concentration of 3 muM). Importantly, the pharmacokinetic properties of 20 (F = 36%) represented a marked improvement over that of the initial 2,4-diarylimidazole structures.

  DOI：

  10.1021/jm030490g
• 作为产物：
  描述：

  2-氨基-1-(3-三氟甲基苯基)乙酮盐酸盐 、 环己甲酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Cyclohexanecarboxylic acid [2-oxo-2-(3-trifluoromethyl-phenyl)-ethyl]-amide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Substituted 2-Cyclohexyl-4-phenyl-1H-imidazoles:  Potent and Selective Neuropeptide Y Y5-Receptor Antagonists

  摘要：

  Antagonizing the robust stimulation of food intake by neuropeptide Y represents a new potential therapeutic approach for the treatment of obesity. Earlier pharmacological studies have pointed to the Y1 and Y5 receptors as the most likely mediators of the NPY orexigenic response. In this paper, we describe a new series of small molecule Y5 antagonists derived from a 2,4diaryl-1H-imidazole lead. The main objectives of our structural optimization efforts were to produce novel and potent Y5 antagonists with an improved oral pharmacokinetic profile and less affinity for the hERG potassium channel compared to the lead 2,4-diarylimidazole structures. These goals were accomplished by replacement of the 2-aryl ring with a cyclohexyl ring and subsequent elaboration of the 4-position of the cyclohexyl ring with a variety of hydrophilic functionalities. The resulting compound, N-(2-hydroxy-tert-butyl)(4-{4-[3-(trifluoro-methyl)phenyl]imidazol-2-yl}cyclohexyl)carboxamide (20), displayed good potency at the Y5 receptor (K-i = 3 nM), while interactions at the hERG channel were essentially eliminated (6% inhibition at a concentration of 3 muM). Importantly, the pharmacokinetic properties of 20 (F = 36%) represented a marked improvement over that of the initial 2,4-diarylimidazole structures.

  DOI：

  10.1021/jm030490g

文献信息

• P70 S6 KINASE INHIBITORS
  申请人：Dally Robert Dean

  公开号：US20120071490A1

  公开（公告）日：2012-03-22

  The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.

  本发明提供了公式为：p70 S6激酶抑制剂的制剂，以及包含它们的药物制剂和使用它们的方法。
• US8093383B2
  申请人：——

  公开号：US8093383B2

  公开（公告）日：2012-01-10
• Design, Synthesis, and Biological Evaluation of Substituted 2-Cyclohexyl-4-phenyl-1<i>H</i>-imidazoles:  Potent and Selective Neuropeptide Y Y5-Receptor Antagonists
  作者：Charles A. Blum、Xiaozhang Zheng、Stéphane De Lombaert

  DOI：10.1021/jm030490g

  日期：2004.4.1

  Antagonizing the robust stimulation of food intake by neuropeptide Y represents a new potential therapeutic approach for the treatment of obesity. Earlier pharmacological studies have pointed to the Y1 and Y5 receptors as the most likely mediators of the NPY orexigenic response. In this paper, we describe a new series of small molecule Y5 antagonists derived from a 2,4diaryl-1H-imidazole lead. The main objectives of our structural optimization efforts were to produce novel and potent Y5 antagonists with an improved oral pharmacokinetic profile and less affinity for the hERG potassium channel compared to the lead 2,4-diarylimidazole structures. These goals were accomplished by replacement of the 2-aryl ring with a cyclohexyl ring and subsequent elaboration of the 4-position of the cyclohexyl ring with a variety of hydrophilic functionalities. The resulting compound, N-(2-hydroxy-tert-butyl)(4-4-[3-(trifluoro-methyl)phenyl]imidazol-2-yl}cyclohexyl)carboxamide (20), displayed good potency at the Y5 receptor (K-i = 3 nM), while interactions at the hERG channel were essentially eliminated (6% inhibition at a concentration of 3 muM). Importantly, the pharmacokinetic properties of 20 (F = 36%) represented a marked improvement over that of the initial 2,4-diarylimidazole structures.