| 1403950-72-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1403950-72-0
• 化学式: C₃₁H₄₁N₃O₃Si
• 分子量: 531.77
• InChiKey: XLJXWCMDYDKKKW-RYOBIWAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.96
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  56.59
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以96%的产率得到
  参考文献：
  名称：

  Synthesis and SAR Studies of Fused Oxadiazines as γ-Secretase Modulators for Treatment of Alzheimer's Disease

  摘要：

  Fused oxadiazines (3) were discovered as selective and orally bioavailable gamma-secretase modulators (GSMs) based on the structural framework of oxadiazoline GSMs. Although structurally related, initial modifications showed that structure-activity relationships (SARs) did not translate from the oxadiazoline to the oxadiazine series. Subsequent SAR studies on modifications at the C3 and C4 positions of the fused oxadiazine core helped to identify GSMs such as compounds 8r and 8s that were highly efficacious in vitro and in vivo in a number of animal models with highly desirable physical and pharmacological properties. Further improvements of in vitro activity and selectivity were achieved by the preparation of fused morpholine oxadiazines. The shift in specificity of APP cleavage rather than a reduction in overall gamma-secretase activity and the lack of changes in substrate accumulation and Notch processing as observed in the animal studies of compound 8s confirm that the oxadiazine series of compounds are potent GSMs.

  DOI：

  10.1021/ml300209g
• 作为产物：
  描述：

  (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)piperidin-2-one 在 伯吉斯试剂 、 叔丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Synthesis and SAR Studies of Fused Oxadiazines as γ-Secretase Modulators for Treatment of Alzheimer's Disease

  摘要：

  Fused oxadiazines (3) were discovered as selective and orally bioavailable gamma-secretase modulators (GSMs) based on the structural framework of oxadiazoline GSMs. Although structurally related, initial modifications showed that structure-activity relationships (SARs) did not translate from the oxadiazoline to the oxadiazine series. Subsequent SAR studies on modifications at the C3 and C4 positions of the fused oxadiazine core helped to identify GSMs such as compounds 8r and 8s that were highly efficacious in vitro and in vivo in a number of animal models with highly desirable physical and pharmacological properties. Further improvements of in vitro activity and selectivity were achieved by the preparation of fused morpholine oxadiazines. The shift in specificity of APP cleavage rather than a reduction in overall gamma-secretase activity and the lack of changes in substrate accumulation and Notch processing as observed in the animal studies of compound 8s confirm that the oxadiazine series of compounds are potent GSMs.

  DOI：

  10.1021/ml300209g