((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 carbamate | 1579953-04-0

• 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,4aS,6R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)methyl carbamate
• CAS: 1579953-04-0
• 化学式: C₂₂H₂₇BrN₂O₄
• 分子量: 463.371
• InChiKey: SAQUDEGWQXYUMI-ZZBGHRQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  91.51
• 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,4aS,6R,8aR,9S,9aS)-9-((E)-2-(5-bromopyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)methyl carbamate 在 dirhodium tetraacetate 、 四(三苯基膦)钯 、 碘苯二乙酸 、 magnesium oxide 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 1.5h， 生成 2-(6-((E)-2-((1R,3aR,4aR,4'S,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：

  (3R,3aS,4S,4aR,7R,8aS,9aR)-7-(hydroxymethyl)-3-methyl-4-((E)-2-(5-(3-(trifluoromethyl)phenyl)pyridin-2-yl)vinyl)decahydronaphtho[2,3-c]furan-1(3H)-one 在 甲醇 、 4-二甲氨基吡啶 、 potassium carbonate 、 臭氧 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 ((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 carbamate
  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