2-[2-(thiophen-2-yl)quinazolin-4-ylamino]ethyl pivalate | 1224625-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[2-(thiophen-2-yl)quinazolin-4-ylamino]ethyl pivalate
• 英文别名: 2-[(2-Thiophen-2-ylquinazolin-4-yl)amino]ethyl 2,2-dimethylpropanoate
• CAS: 1224625-24-4
• 化学式: C₁₉H₂₁N₃O₂S
• 分子量: 355.461
• InChiKey: CWBDHPBJMCSXRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[2-(thiophen-2-yl)quinazolin-4-ylamino]ethyl pivalate 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.25h， 生成 2-{methyl[2-(thiophen-2-yl)quinazolin-4-yl]amino}ethanol
  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：

  2-[(2-氯喹-4-唑啉)氨基]乙醇 在 四(三苯基膦)钯 、 potassium carbonate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 16.5h， 生成 2-[2-(thiophen-2-yl)quinazolin-4-ylamino]ethyl pivalate
  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

文献信息

• Evaluation of Quinazoline Analogues as Glucocerebrosidase Inhibitors with Chaperone Activity
  作者：Juan J. Marugan、Wei Zheng、Omid Motabar、Noel Southall、Ehud Goldin、Wendy Westbroek、Barbara K. Stubblefield、Ellen Sidransky、Ronald A. Aungst、Wendy A. Lea、Anton Simeonov、William Leister、Christopher P. Austin

  DOI：10.1021/jm1008902

  日期：2011.2.24

  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.