(1S,8S,9S,10R,13S,14S)-1-(4-Amino-phenylsulfanyl)-10,13-dimethyl-1,8,9,10,11,12,13,14,15,16-decahydro-2H-cyclopenta[a]phenanthrene-3,17-dione | 110325-38-7

• 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: (1S,8S,9S,10R,13S,14S)-1-(4-Amino-phenylsulfanyl)-10,13-dimethyl-1,8,9,10,11,12,13,14,15,16-decahydro-2H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 110325-38-7
• 化学式: C₂₅H₂₉NO₂S
• 分子量: 407.577
• InChiKey: SBJSXGMFIPJBDK-FGBLIBFFSA-N

物化性质

• 沸点：
  627.8±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  29.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  60.16
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  雄甾-1,4,6-三烯-3,17-二酮 、 4-氨基苯硫酚 在 盐酸 、 溶剂黄146 作用下， 反应 24.0h， 以30%的产率得到(1S,8S,9S,10R,13S,14S)-1-(4-Amino-phenylsulfanyl)-10,13-dimethyl-1,8,9,10,11,12,13,14,15,16-decahydro-2H-cyclopenta[a]phenanthrene-3,17-dione
  参考文献：
  名称：

  7种α-取代的雄甾烯-1,4-二烯-3,17-二酮作为酶激活的芳香酶不可逆抑制剂的合成和生化研究。

  摘要：

  雄烯二酮的几种7种α-硫代取代衍生物已显示出对芳香酶的有效抑制作用，芳香酶是负责雌激素生物合成的细胞色素P450酶复合物。在A环中引入一个额外的双键产生7个α-（4'-氨基）苯硫基雄烷-1,4-二烯-3,17-二酮（7 alpha-APTADD），一种有效的抑制剂，可通过一种酶使芳香酶失活-催化过程。设计了另外的7种α-硫代取代的androsta-1,4-diene-3,17-dione衍生物，以进一步检查酶催化的失活。通过酸催化的取代苯硫酚与Androsta-1,4,6-三烯-3,17-二酮的共轭迈克尔加成反应合成了两个卤代和一个未取代的7α-苯基硫代雄烷-1,4-二烯-3,17-二酮。两个7α-萘基硫代雄烷-1,4-二烯-3，通过酸催化或基于碱催化的取代的噻吩酚与雄甾烯-1,4,6-三烯-3,17-二酮的共轭迈克尔加成反应合成17-二酮。评价了这些试剂在人胎盘微粒体制剂中的芳香酶抑制活

  DOI：

  10.1016/0039-128x(93)90081-w

文献信息

• 7 α -Substituted androstenediones as effective in vttro and invivo inhibitors of aromatase
  作者：Robert W. Brueggemeier、Li Pui-Kai、Catherine E. Snider、Michael V. Darby、Nancy E. Katlic

  DOI：10.1016/0039-128x(83)90069-7

  日期：1987.7

  Research efforts over the past several years have focused on the synthesis of competitive and irreversible aromatase inhibitors and examination of these inhibitors in microsomal preparations, in cell culture, and in vivo. Several 7 alpha-substituted androstenediones have demonstrated high affinity for placental aromatase, with apparent Ki's ranging from 1 to 30 nM. Inactivation of aromatase occurred following incubation with alkylating and enzyme-activated irreversible inhibitors. 7 alpha-(4'-Amino)phenylthio-4-androstene-3,17-dione (7 alpha-APTA) exhibits potent inhibitory activity of aromatase in the MCF-7 human mammary carcinoma cell line with an ED50 of approximately 25 nM. The inhibitor did not bind to the estrogen receptor of the cells in vitro nor induce levels of progesterone receptors in intact cells. In vivo studies of 7 alpha-APTA in the DMBA-induced rat mammary carcinoma model resulted in 80% of the tumors responding completely or partially at doses of 25 and 50 mg/kg body wt/day. Thus, these 7 alpha-substituted steroidal aromatase inhibitors are effective medicinal agents and may be useful for the treatment of estrogen-dependent breast cancer.