4-hydroxyandrosta-4,6-diene-3,17-dione | 89617-12-9

• 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-hydroxyandrosta-4,6-diene-3,17-dione
• 英文别名: (8R,9S,10R,13S,14S)-4-hydroxy-10,13-dimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 89617-12-9
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: XMFHKAIGHZYAME-KZQROQTASA-N

物化性质

• 沸点：
  495.0±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 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：

  4-hydroxyandrosta-4,6-diene-3,17-dione 在 吡啶 、 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， 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：

  4-methoxy-4-androstene-3,17-dione 在 N-溴代丁二酰亚胺(NBS) 、 column of silica 、 过氧化苯甲酰 作用下， 生成 4-hydroxyandrosta-4,6-diene-3,17-dione
  参考文献：
  名称：

  Mann, John; Pietrzak, Barbara, Journal of the Chemical Society. Perkin transactions I, 1983, # 11, p. 2681 - 2685

  摘要：

  DOI：

文献信息

• C-6α- vs C-7α-Substituted Steroidal Aromatase Inhibitors: Which Is Better? Synthesis, Biochemical Evaluation, Docking Studies, and Structure–Activity Relationships
  作者：Fernanda M. F. Roleira、Carla Varela、Cristina Amaral、Saul C. Costa、Georgina Correia-da-Silva、Federica Moraca、Giosuè Costa、Stefano Alcaro、Natércia A. A. Teixeira、Elisiário J. Tavares da Silva

  DOI：10.1021/acs.jmedchem.9b00157

  日期：2019.4.11

  C-6α and C-7α androstanes were studied to disclose which position among them is more convenient to functionalize to reach superior aromatase inhibition. In the first series, the study of C-6 versus C-7 methyl derivatives led to the very active compound 9 with IC50 of 0.06 μM and Ki = 0.025 μM (competitive inhibition). In the second series, the study of C-6 versus C-7 allyl derivatives led to the best

  研究了C-6α和C-7α雄烷酮，以揭示其中的哪个位置更易于官能化以实现优异的芳香化酶抑制作用。在第一个系列中，对C-6和C-7甲基衍生物的研究导致了非常活泼的化合物9，IC50为0.06μM，Ki = 0.025μM（竞争性抑制）。在第二系列中，对C-6和C-7烯丙基衍生物的研究导致了这项工作中最佳的芳香化酶抑制剂13，IC50为0.055μM，Ki = 0.0225μM（不可逆抑制）。除了这些发现外，可以得出结论，C-6α位置比C-7α更好的功能化，除了同时存在一个C-4取代基时。另外，甲基是最好的取代基，其次是烯丙基，其次是羟基。为了合理化最佳抑制剂13的构效关系，
• Estrogen synthesis inhibitors
  申请人：THE ROCKEFELLER UNIVERSITY

  公开号：EP0161492A2

  公开（公告）日：1985-11-21

  Invention relates to 3-methylene substituted androst-4- ene-17-oxygenated compounds substituted with various substituents at the 10β-position which are useful as inhibitors of estrogen biosynthesis.

  本发明涉及在 10β 位上被各种取代基取代的 3-亚甲基取代雄-4-烯-17-氧化合物，这些化合物可用作雌激素生物合成的抑制剂。
• Synthesis and evaluation of novel 4-amino-4,6-androstadiene-3,17-dione: An analog of formestane
  作者：Sanjay K. Sharma、Weizhong Zheng、Alummoottil V. Joshua、Douglas N. Abrams、Alexander J.B. McEwan

  DOI：10.1016/j.bmcl.2008.09.018

  日期：2008.10

  Synthesis of 4-amino-4,6-androstadiene-3,17-dione 7, an analog of formestane used in breast cancer therapy as an aromatase inhibitor, from 4-acetoxy-4-androstene-3,17-dione 2 is described. This is the first report of a 4-amino diene (4,6) system in this series of molecules. The new (7) and reported molecules were screened by the National Cancer Institute (NCI, Bethesda, USA) for in vitro antitumor activity against 60 human cancer cell lines. Molecule 7 showed best activity against breast cancer cell line (MCF-7). (c) 2008 Elsevier Ltd. All rights reserved.
• DE744995
  申请人：——

  公开号：——

  公开（公告）日：——
• SUBSTITUTED ANDROST-4-ENE DIONES
  申请人：Emory University

  公开号：EP2556082A2

  公开（公告）日：2013-02-13