2-(3-((tert-butyldimethylsilyl)oxy)propyl)-6-methoxy-2-methylchroman-4-one | 1369628-46-5

• 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)-6-methoxy-2-methylchroman-4-one
• 英文别名: 2-(3-((Tert-butyldimethylsilyl)oxy)propyl)-6-methoxy-2-methylchroman-4-one；2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-6-methoxy-2-methyl-3H-chromen-4-one
• CAS: 1369628-46-5
• 化学式: C₂₀H₃₂O₄Si
• 分子量: 364.557
• InChiKey: AARXHMCFWLQVMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-((tert-butyldimethylsilyl)oxy)propyl)-6-methoxy-2-methylchroman-4-one 在 劳森试剂 、 叔丁基过氧化氢 、 dirhodium tetraacetate 、 ammonium hydroxide 、 四(三苯基膦)钯 、 2-naphthalenesulphonyl azide 、 四丁基氟化铵 、 sodium methylate 、 三溴化硼 、 sodium carbonate 、 potassium carbonate 、 sodium hydrogensulfite 、 二乙胺 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 82.0h， 生成 (4S*,4a'S*,10a'R*)-2-amino-8'-(2-fluoropyridin-3-yl)-1,4a'-dimethyl-3',4',4a',10a'-tetrahydro-2'H-spiro[imidazole-4,10'-pyrano[3,2-b]chromen]-5(1H)-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 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 2-(3-((tert-butyldimethylsilyl)oxy)propyl)-6-methoxy-2-methylchroman-4-one
  参考文献：
  名称：

  [EN] HETEROCYCLIC INHIBITORS OF BETA - SECRETASE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  [FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA BÊTA-SECRÉTASE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES

  摘要：

  本发明提供了一种抑制β-分泌酶裂解APP的新颖三环化合物，式I'，可用作治疗神经退行性疾病的治疗剂。

  公开号：

  WO2012071458A1

文献信息

• COMPOUNDS FOR TREATING NEURODEGENERATIVE DISEASES
  申请人：Cook Adam

  公开号：US20120157448A1

  公开（公告）日：2012-06-21

  The invention provides novel tricyclic compounds of Formula I′ that inhibit β-secretase cleavage of APP and are useful as therapeutic agents for treating neurodegenerative diseases.

  该发明提供了一种新型三环化合物I'的公式，它能够抑制β-分泌酶对APP的剪切，并且可用作治疗神经退行性疾病的治疗剂。
• [EN] COMPOUNDS FOR TREATING NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS DE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2012040641A3

  公开（公告）日：2012-06-07
• [EN] HETEROCYCLIC INHIBITORS OF BETA - SECRETASE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA BÊTA-SECRÉTASE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2012071458A1

  公开（公告）日：2012-05-31

  The invention provides novel tricyclic compounds of Formula I' that inhibit β-secretase cleavage of APP and are useful as therapeutic agents for treating neurodegenerative diseases.

  本发明提供了一种抑制β-分泌酶裂解APP的新颖三环化合物，式I'，可用作治疗神经退行性疾病的治疗剂。
• 8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors
  作者：Allen A. Thomas、Kevin W. Hunt、Brad Newhouse、Ryan J. Watts、Xingrong Liu、Guy Vigers、Darin Smith、Susan P. Rhodes、Karin D. Brown、Jennifer N. Otten、Michael Burkard、April A. Cox、Mary K. Geck Do、Darrin Dutcher、Sumeet Rana、Robert K. DeLisle、Kelly Regal、Albion D. Wright、Robert Groneberg、Jiangpeng Liao、Kimberly Scearce-Levie、Michael Siu、Hans E. Purkey、Joseph P. Lyssikatos

  DOI：10.1021/jm5015132

  日期：2014.12.11

  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).