(3R,3aS,4S,4aR,7R,8aS,9aR)-4-((E)-2-(5-bromopyridin-2-yl)vinyl)-7-(hydroxymethyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one | 1579953-02-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: (3R,3aS,4S,4aR,7R,8aS,9aR)-4-((E)-2-(5-bromopyridin-2-yl)vinyl)-7-(hydroxymethyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one
• CAS: 1579953-02-8
• 化学式: C₂₁H₂₆BrNO₃
• 分子量: 420.346
• InChiKey: YQEZMLBLFORUFG-ZZBGHRQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  59.42
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3R,3aS,4S,4aR,7R,8aS,9aR)-4-((E)-2-(5-bromopyridin-2-yl)vinyl)-7-(hydroxymethyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one 在 dirhodium tetraacetate 、 四(三苯基膦)钯 、 碘苯二乙酸 、 magnesium oxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (1'R,3'aR,4S,4'aR,8'aR,9'S,9'aS)-1'-methyl-9'-[(E)-2-(5-pyridin-2-ylpyridin-2-yl)ethenyl]spiro[1,3-oxazolidine-4,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-2,3'-dione
  参考文献：
  名称：

  Himbacine-Derived Thrombin Receptor Antagonists: C₇-Spirocyclic Analogues of Vorapaxar

  摘要：

  We have synthesized several C-7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K-i = 5.1 nM). We also present a model of these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some of the structure activity relationships in this series.

  DOI：

  10.1021/ml500008w
• 作为产物：
  描述：

  ((1R,3aR,4aS,6R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)methyl acetate 在 甲醇 、 potassium carbonate 作用下， 反应 1.5h， 以99%的产率得到(3R,3aS,4S,4aR,7R,8aS,9aR)-4-((E)-2-(5-bromopyridin-2-yl)vinyl)-7-(hydroxymethyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one
  参考文献：
  名称：

  Himbacine-Derived Thrombin Receptor Antagonists: C₇-Spirocyclic Analogues of Vorapaxar

  摘要：

  We have synthesized several C-7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K-i = 5.1 nM). We also present a model of these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some of the structure activity relationships in this series.

  DOI：

  10.1021/ml500008w