(4R,4aR,10aR)-4a-ethyl-4,7-dihydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one | 1132656-42-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4R,4aR,10aR)-4a-ethyl-4,7-dihydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one
• 英文别名: (4R,4aR,10aR)-4a-ethyl-4,7-dihydroxy-1,3,4,9,10,10a-hexahydrophenanthren-2-one
• CAS: 1132656-42-8
• 化学式: C₁₆H₂₀O₃
• 分子量: 260.333
• InChiKey: WREMMBCUNVQTFU-HFBAOOFYSA-N

物化性质

• 沸点：
  455.7±45.0 °C(predicted)
• 密度：
  1.225±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R,4aR,10aR)-4a-ethyl-4,7-dihydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one 、 丙炔 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.25h， 生成 (2S,4R,4aR,10aR)-4a-ethyl-2-prop-1-ynyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,4,7-triol
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v
• 作为产物：
  描述：

  (1R,10R,13S,15S)-5-[tert-butyl(dimethyl)silyl]oxy-1-ethyl-14-oxatetracyclo[8.5.0.02,7.013,15]pentadeca-2(7),3,5-trien-12-one 在 水 、 氢化铝 、 mercury dichloride 、 sodium hydroxide 作用下， 以 乙醚 、 乙醇 、 乙酸乙酯 为溶剂， 反应 4.0h， 以20%的产率得到(4R,4aR,10aR)-4a-ethyl-4,7-dihydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v