1,3,7-三甲基-8-(2-苯基乙氧基)嘌呤-2,6-二酮 | 5415-84-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 1,3,7-三甲基-8-(2-苯基乙氧基)嘌呤-2,6-二酮
• 英文名称: 8-(2-phenylethoxy)caffeine
• 英文别名: 1,3,7-trimethyl-8-phenethyloxy-3,7-dihydro-purine-2,6-dione；1,3,7-Trimethyl-8-phenaethyloxy-3,7-dihydro-purin-2,6-dion；8-(3-Phenylethoxy)Caffeine；1,3,7-trimethyl-8-(2-phenylethoxy)purine-2,6-dione
• CAS: 5415-84-9
• 化学式: C₁₆H₁₈N₄O₃
• 分子量: 314.344
• InChiKey: XEJFGTMHCXBIOL-UHFFFAOYSA-N

物化性质

• 熔点：
  144 °C(Solv: ethanol (64-17-5))
• 沸点：
  510.3±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  咖啡因 在 sodium 、 氯 作用下， 以 氯仿 为溶剂， 反应 6.0h， 生成 1,3,7-三甲基-8-(2-苯基乙氧基)嘌呤-2,6-二酮
  参考文献：
  名称：

  8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase

  摘要：

  Recently it was reported that a series of 8-benzyloxycaffeine analogues are potent reversible inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to discover additional C8 oxy substituents of caffeine that lead to potent MAO inhibition, a series of related 8-aryl- and alkyloxycaffeine analogues were synthesized and their MAO-A and -B inhibition potencies were compared to those of the 8-ben-zyloxycaffeines. The results document that while the 8-substituted-oxycaffeine analogues inhibited both human MAO isoforms, they displayed a high degree of selectivity for MAO-B. 8-(3-Phenylpropoxy) caffeine, 8-(2-phenoxyethoxy)caffeine and 8-[(5-methylhexyl)oxy]caffeine were found to be the especially potent MAO-B inhibitors with IC(50) values ranging from 0.38 to 0.62 mu M. These inhibitors are therefore 2.5-4.6 fold more potent MAO-B inhibitors than is 8-benzyloxycaffeine (IC(50) = 1.77 mu M). It is also demonstrated that, analogous to 8-benzyloxycaffeine, halogen substitution on the phenyl ring of the C8 substituent significantly enhances MAO binding affinity. For example, the most potent MAO-B inhibitor of the present series is 8-[2-(4-bromophenoxy)ethoxy]caffeine with an IC(50) value of 0.166 mu M. This study also reports possible binding orientations of selected oxy caffeines within the active site cavities of MAO-A and MAO-B. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.014

文献信息

• 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase
  作者：Belinda Strydom、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.ejmech.2011.05.014

  日期：2011.8

  Recently it was reported that a series of 8-benzyloxycaffeine analogues are potent reversible inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to discover additional C8 oxy substituents of caffeine that lead to potent MAO inhibition, a series of related 8-aryl- and alkyloxycaffeine analogues were synthesized and their MAO-A and -B inhibition potencies were compared to those of the 8-ben-zyloxycaffeines. The results document that while the 8-substituted-oxycaffeine analogues inhibited both human MAO isoforms, they displayed a high degree of selectivity for MAO-B. 8-(3-Phenylpropoxy) caffeine, 8-(2-phenoxyethoxy)caffeine and 8-[(5-methylhexyl)oxy]caffeine were found to be the especially potent MAO-B inhibitors with IC(50) values ranging from 0.38 to 0.62 mu M. These inhibitors are therefore 2.5-4.6 fold more potent MAO-B inhibitors than is 8-benzyloxycaffeine (IC(50) = 1.77 mu M). It is also demonstrated that, analogous to 8-benzyloxycaffeine, halogen substitution on the phenyl ring of the C8 substituent significantly enhances MAO binding affinity. For example, the most potent MAO-B inhibitor of the present series is 8-[2-(4-bromophenoxy)ethoxy]caffeine with an IC(50) value of 0.166 mu M. This study also reports possible binding orientations of selected oxy caffeines within the active site cavities of MAO-A and MAO-B. (C) 2011 Elsevier Masson SAS. All rights reserved.