(2S)-N-((1S,2R)-1-(1,3-benzodioxol-5-ylmethyl)-3-(((4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-c]pyridin]-4'-yl)amino)-2-hydroxypropyl)tetrahydro-2-furancarboxamide | 1089696-43-4

• 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: (2S)-N-((1S,2R)-1-(1,3-benzodioxol-5-ylmethyl)-3-(((4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-c]pyridin]-4'-yl)amino)-2-hydroxypropyl)tetrahydro-2-furancarboxamide
• 英文别名: (2S)-N-[(2S,3R)-1-(1,3-benzodioxol-5-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]oxolane-2-carboxamide
• CAS: 1089696-43-4
• 化学式: C₃₂H₄₃N₃O₆
• 分子量: 565.71
• InChiKey: GYFMZUJFUIFICF-CLPFNFTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2R,3S)-3-amino-4-(benzo[d][1,3]dioxol-5-yl)-1-((S)-6′-neopentyl-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridine]-4′-ylamino)butan-2-ol trichloride 、 (S)-四氢呋喃-2-甲酸 在 N,N'-羰基二咪唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.17h， 以85%的产率得到(2S)-N-((1S,2R)-1-(1,3-benzodioxol-5-ylmethyl)-3-(((4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-c]pyridin]-4'-yl)amino)-2-hydroxypropyl)tetrahydro-2-furancarboxamide
  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

文献信息

• US8552181B2
  申请人：——

  公开号：US8552181B2

  公开（公告）日：2013-10-08