(1R,3aR,4aR,4'R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidine]-2',3(7H)-dione | 1579952-88-7

• 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: (1R,3aR,4aR,4'R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidine]-2',3(7H)-dione
• CAS: 1579952-88-7
• 化学式: C₂₂H₂₅BrN₂O₄
• 分子量: 461.355
• InChiKey: HCMXXOMWCQXNQU-ALFPUFCXSA-N

物化性质

• 沸点：
  692.3±55.0 °C(predicted)
• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  29.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  77.52
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (1R,3aR,4aR,4'R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidine]-2',3(7H)-dione 、 3-氰基苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 3.02h， 以15%的产率得到3-(6-((E)-2-((1R,3aR,4aR,4'R,8aR,9S,9aS)-1-methyl-2',3-dioxodecahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidin]-9-yl)vinyl)pyridin-3-yl)benzonitrile
  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,6S,8aR,9S,9aS)-1-methyl-3-oxo-9-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)dodecahydronaphtho[2,3-c]furan-6-yl)methyl carbamate 在 dirhodium tetraacetate 、 碘苯二乙酸 、 magnesium oxide 、 臭氧 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.09h， 生成 (1R,3aR,4aR,4'R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-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