N'-(2-chloro-7H-purin-6-yl)-3,5-dimethyladamantane-1-carbohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N'-(2-chloro-7H-purin-6-yl)-3,5-dimethyladamantane-1-carbohydrazide
• 英文别名: N'-(2-Chloro-7H-purin-6-yl)-3,5-dimethyladamantane-1-carbohydrazide (9o)
• 化学式: C₁₈H₂₃ClN₆O
• 分子量: 374.873
• InChiKey: RPFBQGFWWOIYEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  95.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 、 3,5-dimethyladamantane-1-carbohydrazide 以 水 为溶剂， 反应 2.0h， 以60%的产率得到N'-(2-chloro-7H-purin-6-yl)-3,5-dimethyladamantane-1-carbohydrazide
  参考文献：
  名称：

  Discovery of novel purine-based heterocyclic P2X7 receptor antagonists

  摘要：

  The pyridine core skeleton of the previously reported dichloropyridine-based potent hP2X(7) receptor antagonist 5 (IC50 = 13 nM in hP2X(7)-expressing HEK293 cells) was modified with various heterocyclic scaffolds. Among the derivatives with quinoline, quinazoline, acridine, and purine scaffolds, the chloropurine-based analog 90 exhibited the most potent antagonistic activity, with an IC50 value of 176 +/- 37 nM in an ethidium bromide uptake assay. In addition, 90 significantly inhibited IL-1 beta release in THP-1 cells stimulated with LPS/IFN-gamma/BzATP (IC50 = 120 +/- 15 nM). Although 90 was less active than the previous antagonist 5, 90 exhibited greatly improved metabolic stability in the in vitro evaluation (71.4% in human, 72.3% in mouse). (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.06.003

文献信息

• Discovery of novel purine-based heterocyclic P2X7 receptor antagonists
  作者：Seung-Hwa Kwak、Won-Gil Lee、Yun-Jin Lee、So-Deok Lee、Yong-Chul Kim、Hyojin Ko

  DOI：10.1016/j.bioorg.2015.06.003

  日期：2015.8

  The pyridine core skeleton of the previously reported dichloropyridine-based potent hP2X(7) receptor antagonist 5 (IC50 = 13 nM in hP2X(7)-expressing HEK293 cells) was modified with various heterocyclic scaffolds. Among the derivatives with quinoline, quinazoline, acridine, and purine scaffolds, the chloropurine-based analog 90 exhibited the most potent antagonistic activity, with an IC50 value of 176 +/- 37 nM in an ethidium bromide uptake assay. In addition, 90 significantly inhibited IL-1 beta release in THP-1 cells stimulated with LPS/IFN-gamma/BzATP (IC50 = 120 +/- 15 nM). Although 90 was less active than the previous antagonist 5, 90 exhibited greatly improved metabolic stability in the in vitro evaluation (71.4% in human, 72.3% in mouse). (C) 2015 Elsevier Inc. All rights reserved.