4β,5β-epoxyandrostan-17-one | 1373116-48-3

• 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: 4β,5β-epoxyandrostan-17-one
• 英文别名: (1S,2R,6S,8R,11R,12S,16S)-2,16-dimethyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadecan-15-one
• CAS: 1373116-48-3
• 化学式: C₁₉H₂₈O₂
• 分子量: 288.43
• InChiKey: RHKHISPXHVJNPF-QXROXWLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  29.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  雄烯二酮 在 甲酸 、 氨 、 双氧水 、 sodium 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.67h， 生成 4α,5α-epoxyandrostan-17-one 、 4β,5β-epoxyandrostan-17-one
  参考文献：
  名称：

  New Structure–Activity Relationships of A- and D-Ring Modified Steroidal Aromatase Inhibitors: Design, Synthesis, and Biochemical Evaluation

  摘要：

  A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3 beta stereochemistry (1, IC50 = 0.18 mu M). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 mu M) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 mu M) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.

  DOI：

  10.1021/jm300262w

文献信息

• Exploring new chemical functionalities to improve aromatase inhibition of steroids
  作者：Carla L. Varela、Cristina Amaral、Georgina Correia-da-Silva、Saul C. Costa、Rui A. Carvalho、Giosuè Costa、Stefano Alcaro、Natércia A.A. Teixeira、Elisiário J. Tavares-da-Silva、Fernanda M.F. Roleira

  DOI：10.1016/j.bmc.2016.04.056

  日期：2016.6

  In this work, new potent steroidal aromatase inhibitors both in microsomes and in breast cancer cells have been found. The synthesis of the 3,4-(ethylenedioxy)androsta-3,5-dien-17-one (12), a new steroid containing a heterocycle dioxene fused in the A-ring, led to the discovery of a new reaction for which a mechanism is proposed. New structure-activity relationships were established. Some 5β-steroids

  在这项工作中，已经发现了微粒体和乳腺癌细胞中新的有效的甾体芳香化酶抑制剂。3,4-（亚乙二氧基）androsta-3,5-dien-17-one（12）的合成是一种新的甾族化合物，其中含有杂环二恶烯稠合在A环中，导致发现了新的反应，提出了一种机制。建立了新的结构-活性关系。一些5β-类固醇（例如化合物4β，5β-环氧雄烷-17-一（9））显示出芳香化酶抑制活性，因为它们采用与芳香化酶天然底物雄烯二酮类似的A环构型。此外，还公开了增加平面度的新化学特征，特别是3α，4α-环丙烷环，如3α，4α-亚甲基-5α-雄烷-17-一（5）（IC50 =0.11μM）和Δ（9 -11）在C环中的双键，如androsta-4,9（11）-diene-3，17-二酮（13）（IC50 =0.25μM）。此外，诱导拟合对接（IFD）模拟和新陈代谢部位（SoM）预测有助于解释该酶中新的有效甾体芳香酶抑制剂的识别
• New Structure–Activity Relationships of A- and D-Ring Modified Steroidal Aromatase Inhibitors: Design, Synthesis, and Biochemical Evaluation
  作者：Carla Varela、Elisiário J. Tavares da Silva、Cristina Amaral、Georgina Correia da Silva、Teresa Baptista、Stefano Alcaro、Giosuè Costa、Rui A. Carvalho、Natércia A. A. Teixeira、Fernanda M. F. Roleira

  DOI：10.1021/jm300262w

  日期：2012.4.26

  A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3 beta stereochemistry (1, IC50 = 0.18 mu M). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 mu M) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 mu M) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.