(S)-3-(tert-butoxycarbonylamino)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxobutyl acetate | 1373754-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (S)-3-(tert-butoxycarbonylamino)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxobutyl acetate
• 英文别名: [(3S)-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxobutyl] acetate
• CAS: 1373754-47-2
• 化学式: C₁₉H₂₅NO₇
• 分子量: 379.41
• InChiKey: GNVFTWVLZGLKIC-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-(tert-butoxycarbonylamino)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxobutyl acetate 在 盐酸 、 camphor-10-sulfonic acid 、 戴斯-马丁氧化剂 、 lithium tri-t-butoxyaluminum hydride 、 N,N-二异丙基乙胺 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 N-[(2S,3R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-[[(4S)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxybutan-2-yl]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：

  1,4-苯并二恶烷-6-甲醛 在 lithium hydroxide monohydrate 、 (1R,2S)-2-tert-butyl-1-((1R,2S)-2-tertbutyl-2,3-dihydro-1H-isophosphindol-1-yl)-2,3-dihydro-1H-isophosphindole 、 isobutyl chloroformate 、 氢溴酸 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 8.75h， 生成 (S)-3-(tert-butoxycarbonylamino)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxobutyl acetate
  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