(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 | 1579953-19-7

• 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,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
• 英文别名: (1'R,3'aR,4'aR,5R,8'aR,9'S,9'aS)-1'-methyl-9'-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]spiro[1,3-oxazolidine-5,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-2,3'-dione
• CAS: 1579953-19-7
• 化学式: C₂₉H₂₉F₃N₂O₄
• 分子量: 526.555
• InChiKey: PGSCOCNPCZRTMR-DAMDKYIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3R,3aS,4S,4aR,7R,8aR,9aR)-7-(azidomethyl)-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 、 三甲基膦 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 0.17h， 生成 (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

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.