(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 | 1373754-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: (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
• 英文别名: tert-butyl (4S,5R)-4-[[3,4-bis(difluoromethoxy)phenyl]methyl]-5-[[[(4S)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 1373754-59-6
• 化学式: C₃₆H₄₉F₄N₃O₆
• 分子量: 695.795
• InChiKey: HLZSHYORZXLTRO-PNIUZAESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  91.4
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (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 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.33h， 生成 N-[(2S,3R)-1-[3,4-bis(difluoromethoxy)phenyl]-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：

  2-氟-5-溴吡啶 在 2,2,6,6-四甲基哌啶 、 盐酸 、 正丁基锂 、 非那明 、 cesium fluoride 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 19.58h， 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