CGP 79318 | 37716-99-7

• 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: CGP 79318
• 英文别名: 3α,4β-dihydroxy-5α-androstane-17-one；3α,4β-dihydroxy-5α-androstan-17-one；3alpha,4beta-Dihydroxy-5alpha-androstan-17-one；(3R,4R,5R,8R,9S,10R,13S,14S)-3,4-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• CAS: 37716-99-7
• 化学式: C₁₉H₃₀O₃
• 分子量: 306.445
• InChiKey: RFMKWBMPDNCUNR-OIXWSJKVSA-N

物化性质

• 熔点：
  232-234 °C(Solv: acetone (67-64-1); hexane (110-54-3))
• 沸点：
  434.4±45.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  CGP 79318 在 sodium 、 二甲基亚砜 、 三乙胺 、 三氟乙酸酐 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 福美司坦
  参考文献：
  名称：

  福美斯坦 5β-环氧化物前体异常环裂解的 X 射线和氘标记研究

  摘要：

  抗肿瘤类固醇福美烷 (4-OHA) 5 的新聚合合成已从 5 α-和 5 β-androst-3-en-17-one 1a 和 1b 的易于获得的差向异构混合物进行，以尝试提高产量改进。对 5 个 α-和 5 个 β-差向异构体 1a 和 1b 应用两步氧化路线，然后进行碱催化异构化，无论是作为混合物还是分开，得到标题化合物 5。从差向异构体 1a 获得了一个有效的过程制备所需的芳香酶抑制剂福美斯坦。差向异构体 1b 导致了相同化合物 5 的形成。此外，1b 也被转化为 5β-羟基雄甾烷-3,17-二酮 12 和雄甾醇-4-烯-3,17-二酮 13，揭示了出乎意料的反应性3 测试版，4 β-epoxy-5 β-androstan-17-one 中间体 6 在与过甲酸的第一个氧化步骤中由 1b 形成。环氧化物 6 的裂解导致了反双轴和反赤道 vic-二醇 7 和 8 以及 1,3-二醇 9。通过

  DOI：

  10.1016/s0039-128x(01)00164-7
• 作为产物：
  描述：

  雄烯二酮 在 甲酸 、 双氧水 、 溶剂黄146 、 锌 作用下， 反应 3.25h， 生成 CGP 79318
  参考文献：
  名称：

  新的A，D环修饰的类固醇作为芳香酶抑制剂的构效关系：设计，合成和生物活性评估。

  摘要：

  抑制芳香酶是预防和治疗乳腺癌的有效方法。设计并合成了新的A，D环修饰的福尔马斯坦和睾丸内酯类固醇类似物，并在体外研究了它们的生化活性，以寻找新的芳香酶抑制剂并深入了解其结构活性关系（SAR）。所有测试的化合物都没有福尔马坦活性。然而，事实证明3-脱氧甾体烯烃3a及其环氧化物衍生物4a是强竞争性芳香酶抑制剂（K（i）分别为50和38 nM，IC50 = 225和145 nM）。根据我们的发现，C-3羰基对于抗芳香化酶活性不是必不可少的，但是5α-立体化学和甾体骨架中的某些平面性是必需的。此外，通过构建δ-内酯六元环对甾体环戊酮D环的修饰降低了抑制效力。根据获得的结果，可以得出结论，芳香化酶活性位点的结合袋需要在类固醇A，B环和D环结构的平面中对于结合至关重要。

  DOI：

  10.1021/jm050129p

文献信息

• Role of human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C3) in the extrahepatic metabolism of the steroidal aromatase inactivator Formestane
  作者：Runlan Wan、Xi Kong、Youzhe Yang、Siwen Tao、Youyou Chen、Alexander Tobias Teichmann、Frank Heinrich Wieland

  DOI：10.1016/j.jsbmb.2019.105527

  日期：2020.4

  The clinical use of the steroidal aromatase inhibitor Formestane (4-hydroxandrostenedione, 4-OHA) in the treatment of advanced ER+ breast cancer has been discontinued, and therefore, interest in this remarkable drug has vanished. As a C-19 sterol, 4-OHA can undergo extensive intracellular metabolism depending on the expression of specific enzymes in the corresponding cells. We used the metabolites

  甾体芳香酶抑制剂福尔坦斯坦（4-羟氧杂戊二酮，4-OHA）在治疗晚期ER +乳腺癌中的临床应用已中止，因此，对这种显着药物的兴趣已消失。作为C-19固醇，4-OHA可以进行大量的细胞内代谢，具体取决于特定酶在相应细胞中的表达。我们使用代谢物4β-羟基雄甾酮，4β-羟基表雄酮及其17β还原衍生物作为标准，以证明存在于细胞培养基中并由分离的酶表达的催化活性。所有的醛基酮还原酶AKR1C1，AKR1C2，AKR1C3和AKR1C4均同时催化4-OHA的3-酮基和Δ4,5双键的还原。使用微尺度热泳的分子对接实验以及对带有底物4-OHA的分离酶的动力学行为的研究证明，AKR1C3对底物具有最高的亲和力，而AKR1C1是最有效的酶。两种酶（AKR1C1和AKR1C3）都在脂肪组织和肺中高表达，表现出3β-HSD活性。4-OHA产生生物活性衍生物的可能性，例如雄激素4-羟基睾丸激素或5α还原的代谢物的一
• Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites
  作者：Maxie Kohler、Maria K. Parr、Georg Opfermann、Mario Thevis、Nils Schlörer、Franz-Josef Marner、Wilhelm Schänzer

  DOI：10.1016/j.steroids.2006.11.018

  日期：2007.3

  4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated.Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandro-stenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry.Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3 beta-hydroxy-5 alpha-androstane-4,17-dione (2) and 3 alpha-hydroxy-5 beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3 xi,4 xi-dihydroxy,-5 xi-androstan-17-one (4, 6-11) except 3 alpha,4 alpha-dihydroxy-5 beta-androstan-17-one (5).Out of the 17 beta-hydroxylated analogs 4-hydroxytestosterone (18), 3 beta,17 beta-dihydroxy-alpha-androstan-4-one (19),3 alpha,17 beta-dihydroxy-5 beta-androstan-4-one (20), 5 alpha-androstane-3 beta,4 beta,17 beta-triol (21), 5 alpha-androstane-3 alpha,4 beta,17 beta-triol (26) and 5 alpha-androstane-3 alpha,4 alpha,17 beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation. (c) 2006 Elsevier Inc. All rights reserved.
• Tavares Da Silva, Elisiario J.; Sa E Melo, Maria L.; Campos Neves, Andre S., Journal of the Chemical Society. Perkin transactions I, 1996, # 14, p. 1649 - 1650
  作者：Tavares Da Silva, Elisiario J.、Sa E Melo, Maria L.、Campos Neves, Andre S.

  DOI：——

  日期：——
• 17-Oxo-5α-androstane-3α,4β-diyl diacetate and 17-oxo-5β-androstane-3α,4β-diyl diacetate
  作者：L. C. R. Andrade、J. A. Paixão、M. J. M. de Almeida、F. M. Fernandes Roleira、E. J. Tavares da Silva

  DOI：10.1107/s0108270104034250

  日期：2005.3.15

  The title compounds, both C23H34O5, are the 5alpha and 5beta configurations of two diacetate epimers. The 5beta-diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 Angstrom(3), responsible for clathrate behaviour. The 5beta-epimer also features some shorter than average bond lengths in the 3alpha,4beta-acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through ab initio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C-H...O interactions.
• 3α-Hydroxy-5α-androstane-4,17-dione
  作者：L. C. R. Andrade、J. A. Paixão、M. J. de Almeida、E. J. Tavares da Silva、M. L. Sá e Melo、A. S. Campos Neves

  DOI：10.1107/s0108270199011877

  日期：1999.12.15

  The asymmetric unit of the title compound, C19H28O3, contains two independent molecules with almost identical geometry. The molecules have a planar 5 alpha configuration as a result of a trans-A/B junction of the rings. The compound crystallizes in a triclinic cell, which is unusual for steroids. The molecules are linked head-to-tail via hydrogen bonds between the ring A hydroxyl group and the ketone group of ring D, forming two independent chains running along the c axis.