N-(4-chlorophenyl)-4-(4-methylbenzyl)-5-oxo-3-(p-tolyl)-4,5-dihydro-1H-1,2,4-triazole-1-carboxamide

• 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-(4-chlorophenyl)-4-(4-methylbenzyl)-5-oxo-3-(p-tolyl)-4,5-dihydro-1H-1,2,4-triazole-1-carboxamide
• 化学式: C₂₄H₂₁ClN₄O₂
• 分子量: 432.909
• InChiKey: BAJPSORGQQMJRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68.92
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  对甲基苯甲酸甲酯 在 hydrazine hydrate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 反应 53.0h， 生成 N-(4-chlorophenyl)-4-(4-methylbenzyl)-5-oxo-3-(p-tolyl)-4,5-dihydro-1H-1,2,4-triazole-1-carboxamide
  参考文献：
  名称：

  Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists

  摘要：

  Cannabinoids are potentially useful for the treatment of several diseases. In the present work, we report the syntheses and biological evaluations of 1,2,4-triazolone derivatives designed using a combined approach of scaffold hopping and pharmacophore-oriented method. These compounds exhibited interesting antagonistic activity to the cannabinoid CBI receptor. The preliminary structure activity relationships were further discussed. In addition, docking simulations were performed on the good bioactive compound 5c and the low potent compound 5d, respectively, on the basis of homology models of the CBI and CB2 receptors, which were constructed based on human beta 2-adrenoreceptor and optimized in a membrane environment by MD simulations. Calculation of the binding modes gave us insights into the structural requirements for improving the cannabinoid receptor bioactivity and selectivity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.018

文献信息

• Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists
  作者：Shuang Han、Fei-Fei Zhang、Xin Xie、Jian-Zhong Chen

  DOI：10.1016/j.ejmech.2013.12.018

  日期：2014.3

  Cannabinoids are potentially useful for the treatment of several diseases. In the present work, we report the syntheses and biological evaluations of 1,2,4-triazolone derivatives designed using a combined approach of scaffold hopping and pharmacophore-oriented method. These compounds exhibited interesting antagonistic activity to the cannabinoid CBI receptor. The preliminary structure activity relationships were further discussed. In addition, docking simulations were performed on the good bioactive compound 5c and the low potent compound 5d, respectively, on the basis of homology models of the CBI and CB2 receptors, which were constructed based on human beta 2-adrenoreceptor and optimized in a membrane environment by MD simulations. Calculation of the binding modes gave us insights into the structural requirements for improving the cannabinoid receptor bioactivity and selectivity. (C) 2013 Elsevier Masson SAS. All rights reserved.