5-cyclopropyl-N-[2-(phenylsulfanyl)phenyl]-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide | 677302-24-8

• 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: 5-cyclopropyl-N-[2-(phenylsulfanyl)phenyl]-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• 英文别名: 5-cyclopropyl-N-(2-phenylsulfanylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 677302-24-8
• 化学式: C₂₃H₁₇F₃N₄OS
• mdl: MFCD04042970
• 分子量: 454.475
• InChiKey: CITVHXYLLVAFCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-环丙基-4,4,4-三氟-1,3-丁二酮 在 水 、 溶剂黄146 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 5-cyclopropyl-N-[2-(phenylsulfanyl)phenyl]-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Discovery, Structure–Activity Relationship, and Biological Evaluation of Noninhibitory Small Molecule Chaperones of Glucocerebrosidase

  摘要：

  A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease.

  DOI：

  10.1021/jm300063b

文献信息

• Discovery, Structure–Activity Relationship, and Biological Evaluation of Noninhibitory Small Molecule Chaperones of Glucocerebrosidase
  作者：Samarjit Patnaik、Wei Zheng、Jae H. Choi、Omid Motabar、Noel Southall、Wendy Westbroek、Wendy A. Lea、Arash Velayati、Ehud Goldin、Ellen Sidransky、William Leister、Juan J. Marugan

  DOI：10.1021/jm300063b

  日期：2012.6.28

  A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease.