(2R,8R,9S,10R,13S,14S)-10,13-dimethyl-2-[2-(4-methylphenyl)ethyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione | 1252645-21-8

• 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)-10,13-dimethyl-2-[2-(4-methylphenyl)ethyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 1252645-21-8
• 化学式: C₂₈H₃₆O₂
• 分子量: 404.593
• InChiKey: ANBPKVJPEXOLMJ-NEKODSHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2R,8R,9S,10R,13S,14S)-10,13-dimethyl-2-[2-(4-methylphenyl)ethyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 19.0h， 生成 (8R,9S,10S,13S,14S)-10,13-dimethyl-2-[2-(4-methylphenyl)ethyl]-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
  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：

  在 Jones reagent 作用下， 以 丙酮 为溶剂， 反应 0.05h， 生成 (2R,8R,9S,10R,13S,14S)-10,13-dimethyl-2-[2-(4-methylphenyl)ethyl]-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
  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

文献信息

• Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids
  作者：Madoka Takahashi、Kouwa Yamashita、Mitsuteru Numazawa

  DOI：10.1016/j.steroids.2010.01.008

  日期：2010.4

  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.