8-(2-phenoxyethoxy)caffeine | 359712-73-5

• 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: 8-(2-phenoxyethoxy)caffeine
• 英文别名: 1,3,7-trimethyl-8-(2-phenoxyethoxy)purine-2,6-dione
• CAS: 359712-73-5
• 化学式: C₁₆H₁₈N₄O₄
• 分子量: 330.343
• InChiKey: QLZYGYDYCYXHIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  76.9
• 氢给体数：
  0
• 氢受体数：
  5

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 8-(2-phenoxyethoxy)caffeine
  参考文献：
  名称：

  The Inhibition of Monoamine Oxidase by 8-(2-Phenoxyethoxy)Caffeine Analogues

  摘要：

  在已报道的化合物中，8-(2-苯氧基乙氧基)咖啡因是一种特别有效的抑制剂，其对 MAO-B 的 IC50 值为 0.383 µM。为了提高该化合物的抑制效力并发现高效的可逆 MAO-B 抑制剂，本研究合成了一系列 8-(2-苯氧基乙氧基)咖啡因类似物，这些类似物在苯氧基环的 C4 上含有不同的取代基，并将其作为人类 MAO-A 和 MAO-B 的抑制剂进行了评估。结果表明，8-(2-苯氧基乙氧基)咖啡因类似物是选择性和可逆的 MAO-B 抑制剂，其中最强的同系物 8-{2-[4-(三氟甲基)苯氧基]乙氧基}咖啡因的 IC50 值为 0.061 μM。这些强效抑制剂是设计帕金森病等神经退行性疾病疗法的有用线索。

  DOI：

  10.1055/s-0032-1323662

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.
• The Inhibition of Monoamine Oxidase by 8-(2-Phenoxyethoxy)Caffeine Analogues
  作者：B. Strydom、J. Bergh、J. Petzer

  DOI：10.1055/s-0032-1323662

  日期：——

  Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC50 value of 0.383 µM towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B. The results show that the 8-(2-phenoxyethoxy)caffeine analogues are selective and reversible MAO-B inhibitors with the most potent homologue, 8-2-[4-(trifluoromethyl)phenoxy]ethoxy}caffeine, exhibiting an IC50 value of 0.061 μM. These highly potent inhibitors are useful leads in the design of therapies for neurodegenerative disorders such as Parkinson’s disease.

  在已报道的化合物中，8-(2-苯氧基乙氧基)咖啡因是一种特别有效的抑制剂，其对 MAO-B 的 IC50 值为 0.383 µM。为了提高该化合物的抑制效力并发现高效的可逆 MAO-B 抑制剂，本研究合成了一系列 8-(2-苯氧基乙氧基)咖啡因类似物，这些类似物在苯氧基环的 C4 上含有不同的取代基，并将其作为人类 MAO-A 和 MAO-B 的抑制剂进行了评估。结果表明，8-(2-苯氧基乙氧基)咖啡因类似物是选择性和可逆的 MAO-B 抑制剂，其中最强的同系物 8-2-[4-(三氟甲基)苯氧基]乙氧基}咖啡因的 IC50 值为 0.061 μM。这些强效抑制剂是设计帕金森病等神经退行性疾病疗法的有用线索。