(2S,3S)-4-(3,4-bis-(difluoromethoxy)phenyl)-3-(tert-butoxycarbonylamino)-2-hydroxybutyl acetate | 1373754-48-3

• 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: (2S,3S)-4-(3,4-bis-(difluoromethoxy)phenyl)-3-(tert-butoxycarbonylamino)-2-hydroxybutyl acetate
• 英文别名: [(2S,3S)-4-[3,4-bis(difluoromethoxy)phenyl]-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl] acetate
• CAS: 1373754-48-3
• 化学式: C₁₉H₂₅F₄NO₇
• 分子量: 455.404
• InChiKey: ZKJCYMCBTRLESF-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S,3S)-4-(3,4-bis-(difluoromethoxy)phenyl)-3-(tert-butoxycarbonylamino)-2-hydroxybutyl acetate 在 camphor-10-sulfonic acid 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 原甲酸三甲酯 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.83h， 生成 (4S,5R)-tertbutyl 4-(3,4-bis(difluoromethoxy)benzyl)-2,2-dimethyl-5-(((S)-6′-neopentyl-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]-pyridine]-4′-ylamino)methyl)oxazolidine-3-carboxylate
  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：

  (S)-tert-butyl 1-(3,4-bis(difluoromethoxy)phenyl)-4-diazo-3-oxobutan-2-ylcarbamate 在 氢溴酸 、 lithium tri-t-butoxyaluminum hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 1.92h， 生成 (2S,3S)-4-(3,4-bis-(difluoromethoxy)phenyl)-3-(tert-butoxycarbonylamino)-2-hydroxybutyl 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