3β,4β-dihydroxy-5α-androstan-17-one | 75560-98-4

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物
• 英文名称: 3β,4β-dihydroxy-5α-androstan-17-one
• 英文别名: CGP 77456；(3S,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: 75560-98-4
• 化学式: C₁₉H₃₀O₃
• 分子量: 306.445
• InChiKey: RFMKWBMPDNCUNR-FQHIZPNPSA-N

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：

  3β,4β-dihydroxy-5α-androstan-17-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 5α-androstan-3β,4β,17β-triol
  参考文献：
  名称：

  Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

  摘要：

  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.

  DOI：

  10.1016/j.steroids.2006.11.018
• 作为产物：
  描述：

  去氢表雄酮 在 platinum(IV) oxide 吡啶 、 chromium(VI) oxide 、 sodium hydroxide 、 氢气 、 溴 作用下， 以 甲醇 为溶剂， 反应 25.25h， 生成 3β,4β-dihydroxy-5α-androstan-17-one
  参考文献：
  名称：

  4β-羟基-3β-对甲苯磺酰氧基和五-5-烯的溶剂分解

  摘要：

  4β-乙酰氧基-或羟基的存在会阻碍3β-对甲苯磺酰氧基雄烷-5-烯在含乙酸钠的乙酸中的溶剂化。溶剂分解的产物包括A-正-3-甲酰基-类固醇，除了在7-酮存在下。

  DOI：

  10.1039/p19800000933

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
• STEROID-CARBONSÄUREESTER, ZUSAMMENSETZUNGEN, ENTHALTEND STEROID-CARBONSÄUREESTER UND VERWENDUNG DIESER BEI LOKAL TOPISCHER APPLIKATION FÜR KOSMETISCHE ODER DERMATOLOGISCHE ZWECKE
  申请人：CHelac Holding GmbH

  公开号：EP3057667A1

  公开（公告）日：2016-08-24
• [DE] STEROID-CARBONSÄUREESTER, ZUSAMMENSETZUNGEN, ENTHALTEND STEROID-CARBONSÄUREESTER UND VERWENDUNG DIESER BEI LOKAL TOPISCHER APPLIKATION FÜR KOSMETISCHE ODER DERMATOLOGISCHE ZWECKE<br/>[EN] STEROID CARBOXYLIC ACID ESTERS, COMPOSITIONS CONTAINING STEROID CARBOXYLIC ACID ESTERS, AND USE OF SAID COMPOSITIONS IN LOCAL TOPICAL APPLICATIONS FOR COSMETIC OR DERMATOLOGICAL PURPOSES<br/>[FR] ESTERS D'ACIDE STÉROÏDE-CARBOXYLIQUE, COMPOSITIONS CONTENANT DES ESTERS D'ACIDE STÉROÏDE-CARBOXYLIQUE ET LEUR UTILISATION DANS UNE APPLICATION LOCALEMENT TOPIQUE À DES FINS COSMÉTIQUES OU DERMATOLOGIQUES
  申请人：CHELAC HOLDING GMBH

  公开号：WO2015055179A1

  公开（公告）日：2015-04-23

  Die Erfindung betrifft die Verwendung eines Steroid-3-Carbonsäureesters, eines Steroid-4-Carbonsäureesters oder eines Steroid-17-Carbonsäureesters eines Steroids, ausgewählt aus der Gruppe der Androstanone, der Androst-4-endione, der Androst-5-en-dione, der Dehydroepiandrosterone, der Androstentrione oder der Testosterone, mit einer Acylgruppe des Carbonsäureesters, wobei R ausgewählt ist aus Alkyl mit mindestens zwei Kohlenstoffatomen oder Cycloalkyl, oder Verwendung einer diese Steroid-Carbonsäureester enthaltenden Zusammensetzung bei lokal topischer Applikation für kosmetische oder dermatologische Zwecke. Darüber hinaus betrifft die vorliegende Erfindung auch Steroid-Carbonsäureester und Zusammensetzungen, enthaltend diese, zur lokal topischen Applikation.
• The solvolysis of 4β-hydroxy-3β-p-tolylsulphonyloxyandrost-5-enes
  作者：James R. Hanson、Harry J. Wadsworth

  DOI：10.1039/p19800000933

  日期：——

  The solvolysis of 3β-p-tolylsulphonyloxyandrost-5-enes in acetic acid containing sodium acetate, is retarded by the presence of a 4β-acetoxy- or hydroxy-group. The products of solvolysis include the A-nor-3-formyl-steroids except in the presence of a 7-ketone.

  4β-乙酰氧基-或羟基的存在会阻碍3β-对甲苯磺酰氧基雄烷-5-烯在含乙酸钠的乙酸中的溶剂化。溶剂分解的产物包括A-正-3-甲酰基-类固醇，除了在7-酮存在下。
• 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.