(2R,8R,9S,10R,13S,14S,17S)-2-benzyl-17-((tert-butyldimethylsilyl)oxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | 1252645-06-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (2R,8R,9S,10R,13S,14S,17S)-2-benzyl-17-((tert-butyldimethylsilyl)oxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one
• CAS: 1252645-06-9
• 化学式: C₃₂H₄₈O₂Si
• 分子量: 492.817
• InChiKey: QRCCULMPBVBISU-YIFCBEOESA-N

物化性质

• 沸点：
  551.5±50.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.38
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (2R,8R,9S,10R,13S,14S,17S)-2-benzyl-17-((tert-butyldimethylsilyl)oxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one 在 盐酸 、 水 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids

  摘要：

  A series of 2-phenylaliphatic-substituted androsta-1,4-diene-3,17-diones (6) as well as their androstenedione derivatives (5) were synthesized as aromatase inhibitors to gain insights of structure-activity relationships of varying the alkyl moiety (C(1) to C(4)) of the 2-phenylaliphatic substituents as well as introducing a methyl- or trifluoromethyl function to p-position of a phenethyl moiety to the inhibitory activity. The inhibitors examined showed a competitive type inhibition. The 2-phenpropylandrosta-1,4-diene 6c was the most powerful inhibitor (K(i): 16.1 nM) among them. Compounds 6c along with the phenethyl derivative 6b caused a time-dependent inactivation of aromatase (k(inact): 0.0293 and 0.0454 min(-1) for 6b and 6c, respectively). The inactivation was prevented by the substrate androstenedione, and no significant effect of L-cysteine on the inactivation was observed in each case. Molecular docking of the phenpropyl compound 6c to aromatase was conducted to demonstrate that the phenpropyl group orients to a hydrophobic binding pocket in the active site to result in the formation of thermodynamically stable enzyme-inhibitor complex. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.01.008
• 作为产物：
  描述：

  溴甲苯 、 17β-[(t-butyldimethylsilyl)oxy]androst-4-en-3-one 在 六甲基磷酰三胺 、 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 以64%的产率得到(2R,8R,9S,10R,13S,14S,17S)-2-benzyl-17-((tert-butyldimethylsilyl)oxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids

  摘要：

  A series of 2-phenylaliphatic-substituted androsta-1,4-diene-3,17-diones (6) as well as their androstenedione derivatives (5) were synthesized as aromatase inhibitors to gain insights of structure-activity relationships of varying the alkyl moiety (C(1) to C(4)) of the 2-phenylaliphatic substituents as well as introducing a methyl- or trifluoromethyl function to p-position of a phenethyl moiety to the inhibitory activity. The inhibitors examined showed a competitive type inhibition. The 2-phenpropylandrosta-1,4-diene 6c was the most powerful inhibitor (K(i): 16.1 nM) among them. Compounds 6c along with the phenethyl derivative 6b caused a time-dependent inactivation of aromatase (k(inact): 0.0293 and 0.0454 min(-1) for 6b and 6c, respectively). The inactivation was prevented by the substrate androstenedione, and no significant effect of L-cysteine on the inactivation was observed in each case. Molecular docking of the phenpropyl compound 6c to aromatase was conducted to demonstrate that the phenpropyl group orients to a hydrophobic binding pocket in the active site to result in the formation of thermodynamically stable enzyme-inhibitor complex. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.01.008