(1R,3aR,4aS,8aS,9S,9aS)-1-methyl-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]-1,3a,4,4a,6,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran-3,5-dione | 226914-91-6

• 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,8aS,9S,9aS)-1-methyl-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]-1,3a,4,4a,6,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran-3,5-dione
• CAS: 226914-91-6
• 化学式: C₂₇H₂₆F₃NO₃
• 分子量: 469.504
• InChiKey: VLQHXCIVSTWIQS-RIHNVNSGSA-N

物化性质

• 沸点：
  623.0±55.0 °C(predicted)
• 密度：
  1.279±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.96
• 重原子数：
  34.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  56.26
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,3aR,4aS,8aS,9S,9aS)-1-methyl-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]-1,3a,4,4a,6,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran-3,5-dione 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 (1R,3aR,4aS,8aS,9S,9aS)-5,5-difluoro-1-methyl-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]-1,3a,4,4a,6,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran-3-one
  参考文献：
  名称：

  THROMBIN RECEPTOR ANTAGONISTS

  摘要：

  公开号：

  EP1036072B1
• 作为产物：
  描述：

  在 盐酸 作用下， 以 丙酮 为溶剂， 生成 (1R,3aR,4aS,8aS,9S,9aS)-1-methyl-9-[(E)-2-[5-[3-(trifluoromethyl)phenyl]pyridin-2-yl]ethenyl]-1,3a,4,4a,6,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran-3,5-dione
  参考文献：
  名称：

  Metabolism-Based Identification of a Potent Thrombin Receptor Antagonist

  摘要：

  The metabolism of our prototypical thrombin receptor antagonist 1, K-i = 2.7 nM, was studied and three major metabolites (2,4, and 5) were found. The structures of the metabolites were verified independently by synthesis. Compound 4 was shown to be a potent antagonist of the thrombin receptor with a K-i = 11 nM. Additionally, compound 4 showed a 3-fold improvement in potency with respect to 1 in an agonist-induced ex-vivo platelet aggregation assay in cynomolgus monkeys after oral administration; this activity was sustained with 60% inhibition observed at 24 h post-dose. Compound 4 was highly active in functional assays and showed excellent oral bioavailability in rats and monkeys. Compound 4 showed a superior rat enzyme induction profile relative to compound 1, allowing it to replace compound 1 as a development candidate.

  DOI：

  10.1021/jm061043e