tert-butyl 4-({5-[4-(4-tosylpiperazin-1-yl)quinazolin-2-yl]thiophen-2-yl}methyl)piperazine-1-carboxylate | 1264534-22-6

• 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: tert-butyl 4-({5-[4-(4-tosylpiperazin-1-yl)quinazolin-2-yl]thiophen-2-yl}methyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-[[5-[4-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]quinazolin-2-yl]thiophen-2-yl]methyl]piperazine-1-carboxylate
• CAS: 1264534-22-6
• 化学式: C₃₃H₄₀N₆O₄S₂
• 分子量: 648.85
• InChiKey: KIFUBJYBVILFLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-({5-[4-(4-tosylpiperazin-1-yl)quinazolin-2-yl]thiophen-2-yl}methyl)piperazine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 以66%的产率得到2-[5-(piperazin-1-ylmethyl)thiophen-2-yl]-4-(4-tosylpiperazin-1-yl)quinazoline
  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
• 作为产物：
  描述：

  1-(甲苯-4-磺酰基)哌嗪 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 tert-butyl 4-({5-[4-(4-tosylpiperazin-1-yl)quinazolin-2-yl]thiophen-2-yl}methyl)piperazine-1-carboxylate
  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