4-mercapto-4-androstene-3,17-dione | 95192-06-6

• 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: 4-mercapto-4-androstene-3,17-dione
• 英文别名: 4-mercaptoandrost-4-ene-3,17-dione；(8R,9S,10R,13S,14S)-10,13-dimethyl-4-sulfanyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 95192-06-6
• 化学式: C₁₉H₂₆O₂S
• 分子量: 318.48
• InChiKey: KIUNBUZCKHWNHF-KZQROQTASA-N

物化性质

• 沸点：
  475.4±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  35.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-mercapto-4-androstene-3,17-dione 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.08h， 生成 17-oxoandrost-3-eno<3,4-b><1,3>oxathiole-5-carbonitrile
  参考文献：
  名称：

  Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors

  摘要：

  A series of new 4-(alkylthio)-substituted androstenedione analogues was designed as potential suicide inhibitors of aromatase on the basis of mechanistic considerations on the mode of action of the enzyme. Their synthesis and biological evaluation are described. Among the most interesting are the 4-[(difluoromethyl)thio]-, 4-[(fluoromethyl) thio]-, and 4-[(chloromethyl)thio]androstenediones 12,13, and 14 with respective IC50's of 2.7,0.8, and 0.94-mu-M. Compound 12 was a reversible inhibitor of aromatase while compounds 13 and 14 displayed time-dependent kinetics of inhibition with respective K(I)'s and half-times of inactivation of 30 nM and 3.75 min for 13 and 30 nM and 3 min for 14. The inhibition of aromatase by 14 was NADPH-dependent, and was protected by the presence of substrate (0.5-1-mu-M), while beta-mercaptoethanol (0.5 mM) failed to protect the enzyme from inactivation. Dialysis failed to reactivate aromatase previously inactivated by 14. The mechanistic implications of these findings are

  DOI：

  10.1021/jm00087a013
• 作为产物：
  描述：

  4-(acetylthio)-5-hydroxyandrost-4-ene-3,17-dione 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 36.0h， 以84%的产率得到4-mercapto-4-androstene-3,17-dione
  参考文献：
  名称：

  Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors

  摘要：

  A series of new 4-(alkylthio)-substituted androstenedione analogues was designed as potential suicide inhibitors of aromatase on the basis of mechanistic considerations on the mode of action of the enzyme. Their synthesis and biological evaluation are described. Among the most interesting are the 4-[(difluoromethyl)thio]-, 4-[(fluoromethyl) thio]-, and 4-[(chloromethyl)thio]androstenediones 12,13, and 14 with respective IC50's of 2.7,0.8, and 0.94-mu-M. Compound 12 was a reversible inhibitor of aromatase while compounds 13 and 14 displayed time-dependent kinetics of inhibition with respective K(I)'s and half-times of inactivation of 30 nM and 3.75 min for 13 and 30 nM and 3 min for 14. The inhibition of aromatase by 14 was NADPH-dependent, and was protected by the presence of substrate (0.5-1-mu-M), while beta-mercaptoethanol (0.5 mM) failed to protect the enzyme from inactivation. Dialysis failed to reactivate aromatase previously inactivated by 14. The mechanistic implications of these findings are

  DOI：

  10.1021/jm00087a013

文献信息

• Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives
  作者：David A. Marsh、Harry J. Brodie、Wesley Garrett、Chon Hwa Tsai-Morris、Angela M. H. Brodie

  DOI：10.1021/jm00383a017

  日期：1985.6

  The synthesis and biological evaluation of androstenedione derivatives as inhibitors of estrogen biosynthesis are described. The results show that 4-hydroxy analogues are among the most potent in vitro inhibitors of the series. Esterification of the 4-hydroxy steroids generally reduced activity. Further conjugation of the 3-keto 4-ene system to give 4-hydroxy-4,6-androstadiene-3,17-dione caused more rapid inactivation of aromatase in rat ovarian microsomes than 4-hydroxyandrostenedione. Some compounds exhibited differences in activity when tested for inhibition of human placental microsomes vs. rat ovarian microsomes. The 4-hydroxyandrostenedione derivatives and their nonbulky esters were generally more potent in vitro and in vivo inhibitors than other substituted steroids in the series. Several of the synthesized compounds markedly reduce (50-81%) estrogen levels in rats on proestrus and/or had antifertility action. To date, none of the compounds surpassed the in vivo inhibitory action of 4-hydroxy-4-androstene-3,17-dione or its 4-acetate derivative.
• ——
  作者：LOMBARDI P.、 DI SALLE E.、 LONGO A.、 ORZI F.

  DOI：——

  日期：——