N-[[(1R,3aR,4aS,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]methyl]methanesulfonamide | 618385-79-8

• 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: N-[[(1R,3aR,4aS,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]methyl]methanesulfonamide
• CAS: 618385-79-8
• 化学式: C₂₈H₃₃FN₂O₄S
• 分子量: 512.645
• InChiKey: PBDJEIKRZRYJAA-NDDAKBLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ((1R,3aR,4aS,6R,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)methyl methanesulfonate 在 sodium azide 、 三乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 5.5h， 生成 N-[[(1R,3aR,4aS,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]methyl]methanesulfonamide
  参考文献：
  名称：

  Himbacine-Derived Thrombin Receptor Antagonists: C₇-Aminomethyl and C_9a-Hydroxy Analogues of Vorapaxar

  摘要：

  We have synthesized several C-7-aminomethyl analogues of vorapaxar that are potent PAR-1 antagonists. Many of these analogues showed excellent in vitro binding affinity and pharmacokinetics profile in rats. Compound 6a from this series showed excellent PAR-1 activity (K-i = 5 nM). We have also synthesized a C-9a-hydroxy analogue of vorapaxar, which showed very good PAR-1 affinity (K-i = 19.5 nM) along with excellent rat pharmacokinetic profile and ex vivo efficacy in the cynomolgus monkey.

  DOI：

  10.1021/ml400452v

文献信息

• Himbacine-Derived Thrombin Receptor Antagonists: C₇-Aminomethyl and C_9a-Hydroxy Analogues of Vorapaxar
  作者：Mariappan V. Chelliah、Samuel Chackalamannil、Yan Xia、William J. Greenlee、Ho-Sam Ahn、Stan Kurowski、George Boykow、Yunsheng Hsieh、Madhu Chintala

  DOI：10.1021/ml400452v

  日期：2014.2.13

  We have synthesized several C-7-aminomethyl analogues of vorapaxar that are potent PAR-1 antagonists. Many of these analogues showed excellent in vitro binding affinity and pharmacokinetics profile in rats. Compound 6a from this series showed excellent PAR-1 activity (K-i = 5 nM). We have also synthesized a C-9a-hydroxy analogue of vorapaxar, which showed very good PAR-1 affinity (K-i = 19.5 nM) along with excellent rat pharmacokinetic profile and ex vivo efficacy in the cynomolgus monkey.