4-hydroxy-1,4,6-androstatriene-3,17-dione | 95192-09-9

• 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: 4-hydroxy-1,4,6-androstatriene-3,17-dione
• 英文别名: 1,4,6-androstatriene-3,17-dione-4-ol；(8R,9S,10R,13S,14S)-4-hydroxy-10,13-dimethyl-9,11,12,14,15,16-hexahydro-8H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 95192-09-9
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: NMSKTPUZMBOAGF-KZQROQTASA-N

物化性质

• 沸点：
  505.7±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 4-hydroxy-1,4,6-androstatriene-3,17-dione 在 吡啶 作用下， 生成 Benzoic acid (8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-4-yl ester
  参考文献：
  名称：

  Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives

  摘要：

  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.

  DOI：

  10.1021/jm00383a017
• 作为产物：
  描述：

  雄甾-1,4-二烯-3,17-二酮 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 20.0h， 以6%的产率得到4-hydroxy-1,4,6-androstatriene-3,17-dione
  参考文献：
  名称：

  Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives

  摘要：

  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.

  DOI：

  10.1021/jm00383a017

文献信息

• 1,4,6-androstatriene-3,17-dione ("ATD") for therapeutic uses
  申请人：Kneller W. Bruce

  公开号：US20060154909A1

  公开（公告）日：2006-07-13

  A composition having modified or derivative of 1,4,6-androstatriene-3,17-dione (“ATD”) will improve the health of mammalian subjects. The improvement of health is achieved with the administration of an effective amount of the at least one modified or derivative of 1,4,6-androstatriene-3,17-dione. Particularly, health is improved for a subject suffering with a gynecomastia, and/or estrogen-dependent cancer. Also, subjects recovering from steroid misuse/abuse with treatment in accordance with the present invention. Other improvements found to occur with an administration of ATD is that growth is enhanced and/or stimulated in developing mammals, recovery is shortened in cases of severe trauma or burns, mood levels are improved, male fertility is improved, and athletic performance is improved by increasing testosterone and lean muscle mass.

  一种含有 1,4,6-雄甾三烯-3,17-二酮（"ATD"）改良剂或衍生物的组合物可改善哺乳动物的健康状况。通过服用有效量的至少一种 1,4,6-雄甾三烯-3,17-二酮的改良物或衍生物，可以改善健康状况。特别是对于患有妇科炎症和/或雌激素依赖性癌症的受试者来说，健康状况会得到改善。此外，根据本发明进行治疗后，滥用类固醇的受试者也能恢复健康。施用 ATD 还能改善其他方面，如促进和/或刺激发育中哺乳动物的生长，缩短严重创伤或烧伤病例的恢复期，改善情绪水平，提高男性生育能力，以及通过增加睾酮和瘦肌肉质量提高运动成绩。
• US7939517B2
  申请人：——

  公开号：US7939517B2

  公开（公告）日：2011-05-10
• 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.