1,3-di-n-propyl-8-(2-nitro-4-chlorophenyl)-8-azaxanthine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,3-di-n-propyl-8-(2-nitro-4-chlorophenyl)-8-azaxanthine
• 英文别名: 2-(4-Chloro-2-nitrophenyl)-4,6-dipropyltriazolo[4,5-d]pyrimidine-5,7-dione
• 化学式: C₁₆H₁₇ClN₆O₄
• 分子量: 392.802
• InChiKey: TVCKXGOZTBVWAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-di-n-propyl-8-(2-nitro-4-chlorophenyl)-8-azaxanthine 在 dimethyl sulfide borane 、 nickel dichloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以60.6%的产率得到2-(2-Amino-4-chloro-phenyl)-4,6-dipropyl-2,4-dihydro-[1,2,3]triazolo[4,5-d]pyrimidine-5,7-dione
  参考文献：
  名称：

  8-Azaxanthine Derivatives as Antagonists of Adenosine Receptors

  摘要：

  A series of 1,3-dimethyl- and 1,3-dipropyl-8-azaxanthines, substituted at the N-8 or N-7 position with substituents which usually increase the affinity of the xanthines for the adenosine receptors, was synthesized and studied in radioligand binding experiments. The substitution of CH with N at the 8-position of both theophylline and caffeine dramatically reduced the affinity, as demonstrated by the fact that 8-azatheophylline and 8-azacaffeine were inert. The introduction of a methyl group at 8-position of 8-azatheophylline restored the antagonistic activity at A(2) receptors, while a 8-cycloalkyl substituent increased the affinity for both receptor subtypes. A more favorable effect on affinity was produced by the substitution of the 7-methyl group in 8-azacaffeine with cycloalkyl groups. 7-Cyclopentyl-1,3-dimethyl-8-azaxanthine was 3 times more potent than caffeine at A(1) receptors and 6 times less active at A(2) receptors. On the contrary, the 7-cyclohexyl-1,3-dimethyl-8-azaxanthine was more potent than caffeine at A(2) receptors. The substitution of 1- and 3-methyl groups with propyl in both 7- and 8-substituted 8-azatheophylline increased remarkably the affinity for A(1) receptors. The 7-cyclopentyl-1,3-dipropyl-8-azaxanthine appears to be one of the most potent and selective among 7-alkyl-substituted xanthines at A(1) receptors so far known. Because the 8-aza analogues of 8-substituted 1,3-dialkylxanthine were in any case less active than the corresponding xanthine derivatives, it was confirmed that the hydrogen atom at the 7-position of xanthines plays an important role in the binding to adenosine receptors.

  DOI：

  10.1021/jm00044a018
• 作为产物：
  描述：

  1,3-di-n-propyl-8-azaxanthine 、 2,5-二氯硝基苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以10.2%的产率得到1,3-di-n-propyl-8-(2-nitro-4-chlorophenyl)-8-azaxanthine
  参考文献：
  名称：

  8-Azaxanthine Derivatives as Antagonists of Adenosine Receptors

  摘要：

  A series of 1,3-dimethyl- and 1,3-dipropyl-8-azaxanthines, substituted at the N-8 or N-7 position with substituents which usually increase the affinity of the xanthines for the adenosine receptors, was synthesized and studied in radioligand binding experiments. The substitution of CH with N at the 8-position of both theophylline and caffeine dramatically reduced the affinity, as demonstrated by the fact that 8-azatheophylline and 8-azacaffeine were inert. The introduction of a methyl group at 8-position of 8-azatheophylline restored the antagonistic activity at A(2) receptors, while a 8-cycloalkyl substituent increased the affinity for both receptor subtypes. A more favorable effect on affinity was produced by the substitution of the 7-methyl group in 8-azacaffeine with cycloalkyl groups. 7-Cyclopentyl-1,3-dimethyl-8-azaxanthine was 3 times more potent than caffeine at A(1) receptors and 6 times less active at A(2) receptors. On the contrary, the 7-cyclohexyl-1,3-dimethyl-8-azaxanthine was more potent than caffeine at A(2) receptors. The substitution of 1- and 3-methyl groups with propyl in both 7- and 8-substituted 8-azatheophylline increased remarkably the affinity for A(1) receptors. The 7-cyclopentyl-1,3-dipropyl-8-azaxanthine appears to be one of the most potent and selective among 7-alkyl-substituted xanthines at A(1) receptors so far known. Because the 8-aza analogues of 8-substituted 1,3-dialkylxanthine were in any case less active than the corresponding xanthine derivatives, it was confirmed that the hydrogen atom at the 7-position of xanthines plays an important role in the binding to adenosine receptors.

  DOI：

  10.1021/jm00044a018