2-((2-(thiophen-2-yl)quinazolin-4-yl)amino)ethan-1-ol | 930909-38-9

• 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-yl)amino)ethan-1-ol
• 英文别名: 2-[2-(thiophen-2-yl)quinazolin-4-ylamino]ethanol；2-[(2-Thiophen-2-ylquinazolin-4-yl)amino]ethanol
• CAS: 930909-38-9
• 化学式: C₁₄H₁₃N₃OS
• 分子量: 271.343
• InChiKey: OZHNAGSJLNTMCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  86.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((2-(thiophen-2-yl)quinazolin-4-yl)amino)ethan-1-ol 在 sodium hydride 、 caesium carbonate 、 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 、 mineral oil 为溶剂， 反应 28.75h， 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：

  2,4-二氯喹唑啉 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 为溶剂， 生成 2-((2-(thiophen-2-yl)quinazolin-4-yl)amino)ethan-1-ol
  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

• [EN] QUINAZOLINE COMPOUNDS AND THE USE THEREOF IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS DE QUINAZOLINE ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：TROBIO THERAPEUTICS PTY LTD

  公开号：WO2021155426A1

  公开（公告）日：2021-08-12

  The present disclosure relates generally to a class of quinazoline compounds, compositions containing the same and the therapeutic use of the compounds in the treatment of cancer.

  本公开涉及一类喹唑啉化合物，包含该化合物的组合物以及化合物在癌症治疗中的治疗用途。
• 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.