(1R,3aR,4aR,4'S,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidine]-2',3(7H)-dione | 1579952-93-4

• 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: (1R,3aR,4aR,4'S,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyloctahydro-1H-spiro[naphtho[2,3-c]furan-6,4'-oxazolidine]-2',3(7H)-dione
• 英文别名: (1'R,3'aR,4S,4'aR,8'aR,9'S,9'aS)-9'-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1'-methylspiro[1,3-oxazolidine-4,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-2,3'-dione
• CAS: 1579952-93-4
• 化学式: C₂₈H₂₉FN₂O₄
• 分子量: 476.548
• InChiKey: XPKRXVRSUORGCI-RSIZQHASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3R,3aS,4S,4aR,7R,8aS,9aR)-4-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-7-(hydroxymethyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one 在 dirhodium tetraacetate 、 碘苯二乙酸 、 magnesium oxide 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 生成 (1R,3aR,4aR,4'S,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-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

文献信息

• Himbacine-Derived Thrombin Receptor Antagonists: C₇-Spirocyclic Analogues of Vorapaxar
  作者：Mariappan V. Chelliah、Keith Eagen、Zhuyan Guo、Samuel Chackalamannil、Yan Xia、Hsingan Tsai、William J. Greenlee、Ho-Sam Ahn、Stan Kurowski、George Boykow、Yunsheng Hsieh、Madhu Chintala

  DOI：10.1021/ml500008w

  日期：2014.5.8

  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.