4α,5α-epoxyandrostan-17-one | 1373116-41-6

• 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: 4α,5α-epoxyandrostan-17-one
• 英文别名: 4alpha,5alpha-Epoxyandrostan-17-one；(1S,2R,6R,8S,11R,12S,16S)-2,16-dimethyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadecan-15-one
• CAS: 1373116-41-6
• 化学式: C₁₉H₂₈O₂
• 分子量: 288.43
• InChiKey: RHKHISPXHVJNPF-BEEALFCHSA-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

• 作为反应物：
  描述：

  4α,5α-epoxyandrostan-17-one 在 盐酸羟胺 、 sodium acetate 作用下， 以 甲醇 为溶剂， 以90%的产率得到(17E)-4α,5α-epoxyandrostan-17-one oxime
  参考文献：
  名称：

  甾体肟的设计、合成和抗肿瘤活性评价

  摘要：

  甾体化合物被证明是对抗多种癌症的有效药物。肟也是经常与抗癌活性相关的化学结构。这项工作的主要目标是通过合成甾体肟并在几种癌细胞系中对其进行评估来组合这两种结构。化合物 (17 E ) -5α-androst -3-en-17-one 肟 ( 3,4 – OLOX ), (17 E )-3α,4α-epoxy-5α-androstan-17-one 肟 ( 3,4 – EPOX ), (17 E )-androst-4-en-17-one 肟 ( 4,5 – OLOX ) 和 (17 E )-4α,5α-epoxyandrostan-17-one 肟 ( 4,5 – EPOX) 被合成并在四种人类癌细胞系中评估它们的细胞毒性，即结肠直肠腺癌 (WiDr)、非小细胞肺癌 (H1299)、前列腺癌 (PC3) 和肝细胞癌 (HepG2)。还使用了人类非肿瘤细胞系 CCD841 CoN（正常结肠细

  DOI：

  10.1016/j.bmc.2021.116360
• 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.
• Design, synthesis, and antitumor activity evaluation of steroidal oximes
  作者：Ana R. Gomes、Ana S. Pires、Ana M. Abrantes、Ana C. Gonçalves、Saul C. Costa、Carla L. Varela、Elisiário T. Silva、Maria F. Botelho、Fernanda M.F. Roleira

  DOI：10.1016/j.bmc.2021.116360

  日期：2021.9

  Steroidal compounds were proven to be efficient drugs against several types of cancer. Oximes are also chemical structures frequently associated with anticancer activity. The main goal of this work was to combine the two referred structures by synthesizing steroidal oximes and evaluating them in several cancer cell lines. Compounds (17E)-5α-androst-3-en-17-one oxime (3,4 – OLOX), (17E)-3α,4α-epoxy

  甾体化合物被证明是对抗多种癌症的有效药物。肟也是经常与抗癌活性相关的化学结构。这项工作的主要目标是通过合成甾体肟并在几种癌细胞系中对其进行评估来组合这两种结构。化合物 (17 E ) -5α-androst -3-en-17-one 肟 ( 3,4 – OLOX ), (17 E )-3α,4α-epoxy-5α-androstan-17-one 肟 ( 3,4 – EPOX ), (17 E )-androst-4-en-17-one 肟 ( 4,5 – OLOX ) 和 (17 E )-4α,5α-epoxyandrostan-17-one 肟 ( 4,5 – EPOX) 被合成并在四种人类癌细胞系中评估它们的细胞毒性，即结肠直肠腺癌 (WiDr)、非小细胞肺癌 (H1299)、前列腺癌 (PC3) 和肝细胞癌 (HepG2)。还使用了人类非肿瘤细胞系 CCD841 CoN（正常结肠细