3-methyl-8-(propan-2-ylsulfanyl)-7-propyl-3,7-dihydro-1H-purine-2,6-dione

• 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: 3-methyl-8-(propan-2-ylsulfanyl)-7-propyl-3,7-dihydro-1H-purine-2,6-dione
• 英文别名: 3-methyl-8-propan-2-ylsulfanyl-7-propylpurine-2,6-dione
• 化学式: C₁₂H₁₈N₄O₂S
• 分子量: 282.367
• InChiKey: UMIFRVGZYVLSKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  92.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氨基-1-甲基尿嘧啶 在 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.0h， 生成 3-methyl-8-(propan-2-ylsulfanyl)-7-propyl-3,7-dihydro-1H-purine-2,6-dione
  参考文献：
  名称：

  Ligand-based design, synthesis and biological evaluation of xanthine derivatives as LSD1/KDM1A inhibitors

  摘要：

  Histone lysine specific demethylase 1 (LSD1) has been recognized as an important epigenetic target for disease treatment. To date, a large number of LSD1 inhibitors have been developed, some of which are currently being evaluated in clinical trials for the treatment of cancers, virus infection, and neurodegenerative diseases. In this paper, we for the first time reported the ligand-based design of fragment-like xanthine derivatives as LSD1 inhibitors, of which compound 4 possessed acceptable pharmacological inhibition against LSD1 (IC50 = 6.45 mu M) and favorable fragment-like nature, and therefore could be used as a promising template to design new LSD1 inhibitors. Interestingly, compounds 6c and 6i strongly suppressed growth of MGC-803 cells partly dependent on their LSD1 inhibition, and were also found to be able to inhibit BRD4 and IDOL. The docking studies were performed to rationalize the biochemical potency against LSD1 and to explain the observed activity discrepancy. The proof-of-concept work may provide an example for other natural ligand-based drug design. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.11.035

文献信息

• Ligand-based design, synthesis and biological evaluation of xanthine derivatives as LSD1/KDM1A inhibitors
  作者：Qi-Sheng Ma、Yongfang Yao、Yi-Chao Zheng、Siqi Feng、Junbiao Chang、Bin Yu、Hong-Min Liu

  DOI：10.1016/j.ejmech.2018.11.035

  日期：2019.1

  Histone lysine specific demethylase 1 (LSD1) has been recognized as an important epigenetic target for disease treatment. To date, a large number of LSD1 inhibitors have been developed, some of which are currently being evaluated in clinical trials for the treatment of cancers, virus infection, and neurodegenerative diseases. In this paper, we for the first time reported the ligand-based design of fragment-like xanthine derivatives as LSD1 inhibitors, of which compound 4 possessed acceptable pharmacological inhibition against LSD1 (IC50 = 6.45 mu M) and favorable fragment-like nature, and therefore could be used as a promising template to design new LSD1 inhibitors. Interestingly, compounds 6c and 6i strongly suppressed growth of MGC-803 cells partly dependent on their LSD1 inhibition, and were also found to be able to inhibit BRD4 and IDOL. The docking studies were performed to rationalize the biochemical potency against LSD1 and to explain the observed activity discrepancy. The proof-of-concept work may provide an example for other natural ligand-based drug design. (C) 2018 Elsevier Masson SAS. All rights reserved.