(1R,2'S,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 | 1579953-11-9

• 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,2'S,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
• CAS: 1579953-11-9
• 化学式: C₂₈H₂₈F₃NO₃
• 分子量: 483.53
• InChiKey: JWSKTWINUGAMBM-AIDUWQDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.16
• 重原子数：
  35.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.72
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,2'S,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 、 N,N-二异丙基乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 生成 (1R,3aR,4aR,5'S,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：

  (3R,3aS,4S,4aR,8aR,9aR)-octahydro-3-methyl-4-[(E)-2-[5-[3-(trifluoromethyl)phenyl]-2-pyridinyl]ethenyl]naphtho[2,3-c]furan-1,7(3H,4H)-dione 、 三甲基碘化锍 在 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 2.25h， 以5%的产率得到(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
  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