8-{[(4-chlorophenyl)sulfanyl]methyl}caffeine | 1388725-92-5

• 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-{[(4-chlorophenyl)sulfanyl]methyl}caffeine
• 英文别名: 8-[(4-chlorophenyl)sulfanylmethyl]-1,3,7-trimethylpurine-2,6-dione
• CAS: 1388725-92-5
• 化学式: C₁₅H₁₅ClN₄O₂S
• 分子量: 350.829
• InChiKey: UMARSZKDTRUYJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  83.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (4-氯苯基硫酚)乙酸 在 盐酸 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 8-{[(4-chlorophenyl)sulfanyl]methyl}caffeine
  参考文献：
  名称：

  Inhibition of monoamine oxidase by 8-phenoxymethylcaffeine derivatives

  摘要：

  A recent study has reported that a series of 8-benzyloxycaffeines are potent and reversible inhibitors of both human monoamine oxidase (MAO) isoforms, MAO-A and -B. In an attempt to discover additional caffeine derivatives with potent MAO inhibitory activities, and to contribute to the known structure-activity relationships of MAO inhibition by caffeine derived compounds, the present study investigates the MAO inhibitory potencies of series of 8-phenoxymethylcaffeine and 8-[(phenylsulfanyl)methyl]caffeine derivatives. The results document that the 8-phenoxymethylcaffeine derivatives act as potent reversible inhibitors of MAO-B, with IC50 values ranging from 0.148 to 5.78 mu M. In contrast, the 8-[(phenylsulfanyl) methyl] caffeine derivatives were found to be weak inhibitors of MAO-B, with IC50 values ranging from 4.05 to 124 mu M. Neither the 8-phenoxymethylcaffeine nor the 8-[(phenylsulfanyl) methyl] caffeine derivatives exhibited high binding affinities for MAO-A. While less potent than the 8-benzyloxycaffeines as MAO-B inhibitors, this study concludes that 8-phenoxymethylcaffeines may act as useful leads for the design of MAO-B selective inhibitors. Such compounds may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Using molecular docking experiments, this study also proposes possible binding orientations of selected caffeine derivatives in the active sites of MAO-A and -B. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.048

文献信息

• Inhibition of monoamine oxidase by 8-phenoxymethylcaffeine derivatives
  作者：Thokozile Okaecwe、Abraham J. Swanepoel、Anél Petzer、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2012.05.048

  日期：2012.7

  A recent study has reported that a series of 8-benzyloxycaffeines are potent and reversible inhibitors of both human monoamine oxidase (MAO) isoforms, MAO-A and -B. In an attempt to discover additional caffeine derivatives with potent MAO inhibitory activities, and to contribute to the known structure-activity relationships of MAO inhibition by caffeine derived compounds, the present study investigates the MAO inhibitory potencies of series of 8-phenoxymethylcaffeine and 8-[(phenylsulfanyl)methyl]caffeine derivatives. The results document that the 8-phenoxymethylcaffeine derivatives act as potent reversible inhibitors of MAO-B, with IC50 values ranging from 0.148 to 5.78 mu M. In contrast, the 8-[(phenylsulfanyl) methyl] caffeine derivatives were found to be weak inhibitors of MAO-B, with IC50 values ranging from 4.05 to 124 mu M. Neither the 8-phenoxymethylcaffeine nor the 8-[(phenylsulfanyl) methyl] caffeine derivatives exhibited high binding affinities for MAO-A. While less potent than the 8-benzyloxycaffeines as MAO-B inhibitors, this study concludes that 8-phenoxymethylcaffeines may act as useful leads for the design of MAO-B selective inhibitors. Such compounds may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Using molecular docking experiments, this study also proposes possible binding orientations of selected caffeine derivatives in the active sites of MAO-A and -B. (C) 2012 Elsevier Ltd. All rights reserved.