N1,N2-dimethyl-N1-[2-(thiophen-2-yl)quinazolin-4-yl]ethane-1,2-diamine | 1222869-97-7

• 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: N1,N2-dimethyl-N1-[2-(thiophen-2-yl)quinazolin-4-yl]ethane-1,2-diamine
• 英文别名: N,N'-dimethyl-N'-(2-thiophen-2-ylquinazolin-4-yl)ethane-1,2-diamine
• CAS: 1222869-97-7
• 化学式: C₁₆H₁₈N₄S
• 分子量: 298.412
• InChiKey: XKMQGXUGGQEXNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N1,N2-dimethyl-N1-[2-(thiophen-2-yl)quinazolin-4-yl]ethane-1,2-diamine 、 对甲苯磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以55%的产率得到N,4-dimethyl-N-(2-{methyl[2-(thiophen-2-yl)quinazolin-4-yl]amino}ethyl)benzenesulfonamide
  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：

  tert-butyl methyl(2-{methyl[2-(thiophen-2-yl)quinazolin-4-yl]amino}ethyl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 以80%的产率得到N1,N2-dimethyl-N1-[2-(thiophen-2-yl)quinazolin-4-yl]ethane-1,2-diamine
  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.