2-(thiophen-2-yl)-6-(4-tosylpiperazin-1-yl)-9H-purine | 1264533-35-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(thiophen-2-yl)-6-(4-tosylpiperazin-1-yl)-9H-purine
• 英文别名: 6-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-2-thiophen-2-yl-7H-purine
• CAS: 1264533-35-8
• 化学式: C₂₀H₂₀N₆O₂S₂
• 分子量: 440.55
• InChiKey: ZRVWUUJDOGOYGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(甲苯-4-磺酰基)哌嗪 在 四(三苯基膦)钯 、 potassium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 100.0 ℃ 、1.38 MPa 条件下， 反应 10.0h， 生成 2-(thiophen-2-yl)-6-(4-tosylpiperazin-1-yl)-9H-purine
  参考文献：
  名称：

  Evaluation of Quinazoline Analogues as Glucocerebrosidase Inhibitors with Chaperone Activity

  摘要：

  Gaucher disease is a lysosomal storage disorder (LSD) caused by deficiency in the enzyme glucocerebrosidase (GC). Small molecule chaperones of protein folding and translocation have been proposed as a promising therapeutic approach to this LSD. Most small molecule chaperones described in the literature contain an iminosugar scaffold. Here we present the discovery and evaluation of a new series of GC inhibitors with a quinazoline core. We demonstrate that this series can improve the translocation of GC to the lysosome in patient-derived cells. To optimize this chemical series, systematic synthetic modifications were performed and the SAR was evaluated and compared using three different readouts of compound activity: enzymatic inhibition, enzyme thermostabilization, and lysosomal translocation of GC.

  DOI：

  10.1021/jm1008902