(3R,3aS,4S,4aR,7R,8aR,9aR)-7-(aminomethyl)-7-hydroxy-3-methyl-4-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)decahydronaphtho[2,3-c]furan-1(3H)-one | 1579953-16-4

• 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,8aR,9aR)-7-(aminomethyl)-7-hydroxy-3-methyl-4-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)decahydronaphtho[2,3-c]furan-1(3H)-one
• CAS: 1579953-16-4
• 化学式: C₂₈H₃₁F₃N₂O₃
• 分子量: 500.561
• InChiKey: CGTSYBONTPANQR-RMKUVKSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  36.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  85.44
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  三光气 、 (3R,3aS,4S,4aR,7R,8aR,9aR)-7-(aminomethyl)-7-hydroxy-3-methyl-4-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)decahydronaphtho[2,3-c]furan-1(3H)-one 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以74%的产率得到(1R,3aR,4aR,5'R,8aR,9S,9aS)-1-methyl-9-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)octahydro-1H-spiro[naphtho[2,3-c]furan-6,5'-oxazolidine]-2',3(7H)-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,2'R,3aR,4aR,8aR,9S,9aS)-1-methyl-9-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)octahydro-1H-spiro[naphtho[2,3-c]furan-6,2'-oxiran]-3(7H)-one 在 sodium azide 、 氯化铵 、 三甲基膦 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R,3aS,4S,4aR,7R,8aR,9aR)-7-(aminomethyl)-7-hydroxy-3-methyl-4-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)decahydronaphtho[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