N-((1S,2S)-2-aminocyclohexyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxamide | 777054-28-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((1S,2S)-2-aminocyclohexyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxamide
• 英文别名: N-[(1S,2S)-2-aminocyclohexyl]-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)imidazole-4-carboxamide
• CAS: 777054-28-1
• 化学式: C₂₂H₂₁Cl₃N₄O
• 分子量: 463.794
• InChiKey: PLEKLOVYPVBULM-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1S,2S)-(+)-1,2-环己二胺 、 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylic acid 在 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 N-((1S,2S)-2-aminocyclohexyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity

  摘要：

  Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K-i = 3.7 nM and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.011