2-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-(hydroxymethylene)-6-methoxy-2-methylchroman-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-(hydroxymethylene)-6-methoxy-2-methylchroman-4-one
• 英文别名: 2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-3-(hydroxymethylidene)-6-methoxy-2-methylchromen-4-one
• 化学式: C₂₁H₃₂O₅Si
• 分子量: 392.568
• InChiKey: BHIVSAPPMWGVAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  64.99
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-(hydroxymethylene)-6-methoxy-2-methylchroman-4-one 在 2-naphthalenesulphonyl azide 、 二乙胺 作用下， 以 乙醚 为溶剂， 反应 18.0h， 以58 g的产率得到2-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-diazo-6-methoxy-2-methylchroman-4-one
  参考文献：
  名称：

  8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors

  摘要：

  A series of 2,3,4,4a,10,10a-hexahydropyrano[3,2-b]chromene analogs was developed that demonstrated high selectivity (>2000-fold) for BACE1 vs Cathepsin D (CatD). Three different Asp-binding moieties were examined: spirocyclic acyl guanidines, aminooxazolines, and aminothiazolines in order to modulate potency, selectivity, efflux, and permeability. Guided by structure based design, changes to P2' and P3 moieties were explored. A conformationally restricted P2' methyl group provided inhibitors with excellent cell potency (37137 nM) and selectivity (435 to >2000-fold) for BACE1 vs CatD. These efforts lead to compound 59, which demonstrated a 69% reduction in rat CSF A beta(1-40) at 60 mg/kg (PO).

  DOI：

  10.1021/jm5015132
• 作为产物：
  描述：

  5-羟基-2-戊酮 在 四氢吡咯 、 咪唑 、 sodium methylate 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 2-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-(hydroxymethylene)-6-methoxy-2-methylchroman-4-one
  参考文献：
  名称：

  8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors

  摘要：

  A series of 2,3,4,4a,10,10a-hexahydropyrano[3,2-b]chromene analogs was developed that demonstrated high selectivity (>2000-fold) for BACE1 vs Cathepsin D (CatD). Three different Asp-binding moieties were examined: spirocyclic acyl guanidines, aminooxazolines, and aminothiazolines in order to modulate potency, selectivity, efflux, and permeability. Guided by structure based design, changes to P2' and P3 moieties were explored. A conformationally restricted P2' methyl group provided inhibitors with excellent cell potency (37137 nM) and selectivity (435 to >2000-fold) for BACE1 vs CatD. These efforts lead to compound 59, which demonstrated a 69% reduction in rat CSF A beta(1-40) at 60 mg/kg (PO).

  DOI：

  10.1021/jm5015132