tert-butyl [(2S,3S)-3-(tert-butyldimethylsilyloxy)-1-(3,4-dimethoxyphenyl)-4-oxobutan-2-yl]carbamate | 1373754-33-6

• 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: tert-butyl [(2S,3S)-3-(tert-butyldimethylsilyloxy)-1-(3,4-dimethoxyphenyl)-4-oxobutan-2-yl]carbamate
• 英文别名: tert-butyl N-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-1-(3,4-dimethoxyphenyl)-4-oxobutan-2-yl]carbamate
• CAS: 1373754-33-6
• 化学式: C₂₃H₃₉NO₆Si
• 分子量: 453.651
• InChiKey: QPWZPAMAJFHSET-FXAWDEMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl [(2S,3S)-3-(tert-butyldimethylsilyloxy)-1-(3,4-dimethoxyphenyl)-4-oxobutan-2-yl]carbamate 在 盐酸 、 N,N-二异丙基乙胺 、 原甲酸三甲酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.33h， 生成 N-((1S,2R)-1-((3,4-bis(methyloxy)phenyl)methyl)-3-(((4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)-2-hydroxypropyl)acetamide
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p
• 作为产物：
  描述：

  magnesium,4-methanidyl-1,2-dimethoxybenzene,chloride 在 盐酸 、 四甲基乙二胺 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.25h， 生成 tert-butyl [(2S,3S)-3-(tert-butyldimethylsilyloxy)-1-(3,4-dimethoxyphenyl)-4-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p