4-aza-17β-hydroxy-5-androsten-3-one | 82093-09-2

• 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-aza-17β-hydroxy-5-androsten-3-one
• 英文别名: 17β-hydroxy-4-aza-androst-5-en-3-one；17β-hydroxy-4-aza-3-oxo-androst-5-ene；17β-hydroxy-4-aza-5-androsten-3-one；17β-Hydroxy-4-aza-androst-5-en-3-on；17β-hydroxy-4-aza-androst-5(6)-en-3-one；17β-hydroxy-4-aza-androst-5-ene-3-one；17beta-Hydroxy-4-aza-androst-5(6)-en-3-one；(1S,3aS,3bR,9aR,9bS,11aS)-1-hydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,6,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinolin-7-one
• CAS: 82093-09-2
• 化学式: C₁₈H₂₇NO₂
• 分子量: 289.418
• InChiKey: YPFXKLVZIQMADQ-MOSWPPPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-aza-17β-hydroxy-5-androsten-3-one 在 platinum(IV) oxide 氢气 作用下， 以 溶剂黄146 为溶剂， 25.0~60.0 ℃ 、310.27 kPa 条件下， 反应 3.0h， 生成 4-Azadihydrotestosterone
  参考文献：
  名称：

  氮杂类固醇作为大鼠前列腺5α-还原酶的抑制剂。

  摘要：

  已经制备了一系列A环杂环类固醇，并在体外测试了其对大鼠前列腺类固醇5α-还原酶的抑制作用。发现一组17个β-取代的4-甲基-4-氮杂-5α-雄甾烷-3-酮具有惊人的高抑制活性。这些化合物由3-酮-δ4前体通过氧化（O3或NaIO4-KMnO4）A环裂解，然后用胺闭环并在铂催化剂上氢化而制得。其他的A环氮杂甾类化合物是通过贝克曼重排2-oxo-A-nor，3-oxo-和4-oxo-5α-雄甾烷酮的肟制得的。通过用间氯过苯甲酸将前体2,3-二氧代-4-氮杂甾族化合物氧化脱羰制备A-正-2-氧代-3-氮杂甾族化合物。4-氮杂类固醇的A环修饰包括δ1-不饱和键，2-和4-取代基以及3-羰基取代基。

  DOI：

  10.1021/jm00378a028
• 作为产物：
  描述：

  3-((3S,3aS,5aS,6R,9aS,9bS)-3-acetoxy-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanoic acid 在 palladium on activated charcoal sodium hydroxide 、 氨 、 氢气 、 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 99.0h， 生成 4-aza-17β-hydroxy-5-androsten-3-one
  参考文献：
  名称：

  Crabb, Trevor A.; Ratcliffe, Norman M., Journal of Chemical Research, Miniprint, 1988, # 7, p. 1601 - 1618

  摘要：

  DOI：

文献信息

• Synthesis and Preliminary Screening of Novel A- and D-Ring Modified Steroids as Aromatase Inhibitors
  作者：Mange Ram Yadav、Prafulla M. Sabale、Rajani Giridhar、Dharmendra Baria、Christina Zimmer、Rolf W. Hartmann

  DOI：10.2174/157018011797655322

  日期：2011.12.1

  Estrogens are responsible for the growth of hormone-dependant breast cancer. Regulation of estrogen biosynthesis is considered as a potential therapeutic strategy for the control of breast cancer. The enzyme aromatase catalyzes conversion of androgens into estrogens in the last step of estrogen biosynthesis. Inhibition of aromatase is adopted as an efficient approach for the prevention and treatment of breast cancer. Many steroidal and nonsteroidal aromatase inhibitors have been developed and are used clinically for breast cancer therapy. In this report, it has been tried to incorporate some structural features (six membered lactam ring) of nonsteroidal aromatase inhibitors like aminoglutethimide and rogletimide into the A-/D-ring of the steroid nucleus with certain additional features responsible for binding to the enzyme aromatase. Some ring-A [17β-hydroxy-4-(4-substitutedphenyl)-4-aza-5-androsten-3-one] and ring-D modified steroidal compounds [4-substituted-17a-aza-D-homo-4-androstene-3,17-dione, 4-substituted-17-aza-Dhomo- 4-androstene-3,16,17a-trione, 4-substituted-17a-methyl-17a-aza-D-homo-4-androsten-3-one] were synthesized and screened for binding to the aromatase enzyme. None of the synthesized compounds showed promising aromatase inhibiting activity leading to the conclusion that structurally the original androstane ring skeleton should not be tampered with, for obtaining good aromatase inhibiting activity.

  雌激素是激素依赖性乳腺癌生长的主要原因。雌激素生物合成的调控已被认为是对乳腺癌进行控制的潜在治疗策略。芳香化酶是一种酶，它促进了雄激素转化为雌激素，这是雌激素生物合成的最后一步。因此，抑制芳香化酶成为预防和治疗乳腺癌的有效方法。现已开发出许多甾体和非甾体类芳香化酶抑制剂，并用于临床乳腺癌治疗。在本报告中，我们试图将一些非甾体类芳香化酶抑制剂（如氨基导眠能和洛格尔替酯）的结构特征（六元内酰胺环）引入甾体母核的A环和D环中，并加入一些能够与芳香化酶结合的结构特征。我们合成了一些A环[17β-羟基-4-(4-取代苯基)-4-氮杂-5-雄甾烯-3-酮]和D环修饰的甾体类化合物[4-取代-17α-氮杂-D-高-4-雄甾烯-3,17-二酮、4-取代-17-氮杂-D-高-4-雄甾烯-3,16,17α-三酮、4-取代-17α-甲基-17α-氮杂-D-高-4-雄甾烯-3-酮]，并测试了它们与芳香化酶的结合能力。然而，合成的化合物均未显示出良好的芳香化酶抑制活性，这表明在结构上，原初的雄甾烷环骨架不应被改动，以获得良好的芳香化酶抑制活性。
• 4-aza steroids
  申请人：Aventis Pharmaceuticals Inc.

  公开号：US06365597B1

  公开（公告）日：2002-04-02

  The invention related to 4-aza-17&bgr;-(cyclopropoxy)-androst-5&agr;-androstan-3-one, 4-aza-17&bgr;-(cyclopropylamino)-androst-4-en-3-one and related compounds and to compositions incorporating these compounds, as well as the inhibition of C17-20 lyase, 5&agr;-reductase and C17&agr;-hydroxylase and to the use of these compounds in the treatment of androgen and estrogen mediated disorders, including benign prostatic hyperplasia, androgen mediated prostate cancer, estrogen mediated breast cancer and to DHT-mediated disorders such as acne. Disorders relating to the oversynthesis of cortisol, for example, Cushing's Syndrome, are also included. The treatment of androgen-dependent disorders also includes a combination therapy with known androgen-receptor antagonists, such as flutamide. The compounds of the invention have the following general formula:

  与4-aza-17β-(环丙氧基)-雄烯-5α-雄烷-3-酮，4-aza-17β-(环丙基氨基)-雄烷-4-烯-3-酮及相关化合物以及含有这些化合物的组合物有关的发明，以及对C17-20裂解酶、5α-还原酶和C17α-羟化酶的抑制，以及利用这些化合物治疗雄激素和雌激素介导的疾病，包括良性前列腺增生、雄激素介导的前列腺癌、雌激素介导的乳腺癌以及DHT介导的疾病，如痤疮。与皮质醇过度合成有关的疾病，例如库欣综合征，也包括在内。治疗雄激素依赖性疾病还包括与已知雄激素受体拮抗剂（如氟他胺）的联合治疗。本发明的化合物具有以下一般公式：
• Eine neue Methode zur Einf�hrung von Stickstoff in das Steroid-Ringsystem: 17?-O-Acetyl-4-aza-oestradiol
  作者：Milan Uskokovi?、Marcel Gut

  DOI：10.1002/hlca.19590420657

  日期：——

  A novel introduction of nitrogen into the 4 position of some common natural steroids is described.

  描述了将氮引入一些常见的天然类固醇的4位的新方法。
• 17-BETA-CYCLOPROPYL(AMINO/OXY) 4-AZA STEROIDS AS ACTIVE INHIBITORS OF TESTOSTERONE 5-ALPHA-REDUCTASE AND C17-20-LYASE
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP0880540B1

  公开（公告）日：2002-06-12
• A microwave promoted and Lewis acid catalysed solventless approach to 4-azasteroids
  作者：Moyurima Borthakur、Romesh C. Boruah

  DOI：10.1016/j.steroids.2008.01.022

  日期：2008.7

  The preparation of 3-oxo-4-azasteroid from A-nor-3,5-secosteroid-3-oic acid is described in a solventless condition catalysed by Lewis acid under microwave irradiation. We utilized urea as an environmentally benign source for the generation of ammonia for the aza cyclization reaction. (C) 2008 Elsevier Inc. All rights reserved.