ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-1-methyl-9-[(E)-2-[5-(5-methylpyridin-2-yl)pyridin-2-yl]ethenyl]-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate | 1258543-08-6

• 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: ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-1-methyl-9-[(E)-2-[5-(5-methylpyridin-2-yl)pyridin-2-yl]ethenyl]-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate
• CAS: 1258543-08-6
• 化学式: C₂₉H₃₅N₃O₄
• 分子量: 489.615
• InChiKey: GSRMVJIJMLMNTC-RMALRHAQSA-N

物化性质

• 沸点：
  692.1±55.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-METHYL-2-PYRIDYLZINC BROMIDE 、 Vorapaxar Bromide Impurity 在 钯 作用下， 生成 ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-1-methyl-9-[(E)-2-[5-(5-methylpyridin-2-yl)pyridin-2-yl]ethenyl]-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate
  参考文献：
  名称：

  Discovery of a vorapaxar analog with increased aqueous solubility

  摘要：

  An analog of the thrombin receptor antagonist vorapaxar (SCH 530348) with increased aqueous solubility, compound 9c (SCH 602539), was discovered through incorporation of polar substituents on the pyridine ring of the himbacine-derived lead series. This analog retained the excellent potency, pharmacokinetic and safety properties of vorapaxar while increasing the aqueous solubility by 20-fold. Also presented are in vivo evaluations of this compound in a cynomolgus monkey platelet aggregation assay and in a Folts model of thrombosis in anesthetized monkeys. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.009

文献信息

• Discovery of a vorapaxar analog with increased aqueous solubility
  作者：Yan Xia、Samuel Chackalamannil、William J. Greenlee、Yuguang Wang、Zhiyong Hu、Yuriko Root、Jesse Wong、Jianshe Kong、Ho-Sam Ahn、George Boykow、Yunsheng Hsieh、Stan Kurowski、Madhu Chintala

  DOI：10.1016/j.bmcl.2010.09.009

  日期：2010.11

  An analog of the thrombin receptor antagonist vorapaxar (SCH 530348) with increased aqueous solubility, compound 9c (SCH 602539), was discovered through incorporation of polar substituents on the pyridine ring of the himbacine-derived lead series. This analog retained the excellent potency, pharmacokinetic and safety properties of vorapaxar while increasing the aqueous solubility by 20-fold. Also presented are in vivo evaluations of this compound in a cynomolgus monkey platelet aggregation assay and in a Folts model of thrombosis in anesthetized monkeys. (C) 2010 Elsevier Ltd. All rights reserved.