3β-hydroxyandrosta-1,5-dien-17-one | 18088-27-2

• 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: 3β-hydroxyandrosta-1,5-dien-17-one
• 英文别名: 3β-Hydroxy-androsta-1,5-dien-17-on；3beta-Hydroxyandrosta-1,5-dien-17-one；Androsta-1,5-dien-17-one, 3-hydroxy-, (3beta)-；(3R,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-3,4,7,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-one
• CAS: 18088-27-2
• 化学式: C₁₉H₂₆O₂
• 分子量: 286.414
• InChiKey: RMHPKSNNHHZEJF-USOAJAOKSA-N

物化性质

• 熔点：
  138-140 °C(Solv: methanol (67-56-1))
• 沸点：
  437.2±45.0 °C(Predicted)
• 密度：
  1.14

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3beta-Acetoxyandrosta-1,5-dien-17-one 在 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以83%的产率得到3β-hydroxyandrosta-1,5-dien-17-one
  参考文献：
  名称：

  C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists

  摘要：

  Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C-19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3 beta,17 beta-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3 beta-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3 beta-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.022

文献信息

• Hydroboration of steroidal-1,5-dien-3.BETA.-ols: A general procedure for the introduction of a hydroxyl group at 1.ALPHA.-position of the 3-oxygenated steroids.
  作者：CHIKARA KANEKO、AKIKO SUGIMOTO、SACHIKO YAMADA、MASAYUKI ISHIKAWA、SATOSHI SASAKI、TATSUO SUDA

  DOI：10.1248/cpb.22.2101

  日期：——

  The procedure used for the preparation of 1α-hydroxycholesterol from cholesta-1, 4-dien-3-one was applied to 17, 17-ethylenedioxyandrosta-1, 4-dien-3-one and 20, 20-ethylenedioxypregna-1, 4-dien-3-one. The successful results described in this paper serve to provide a basis for evaluation of wide scope of this procedure for the introduction of a hydroxyl group at 1α-position of 3-oxygenated steroid derivatives. The procedure consists of three steps starting from 3-keto-△1, 4-steroids available readily from 3-oxygenated steroids : 1) deconjugation to 3-keto-△1, 5-steroids, 2) reduction with metalhydride to 3β-hydroxy-△1, 5-steroids, and 3) hydroboration to 1α, 3β-dihydroxy-△5-steroids. This paper also includes definite identification of the final and intermediate compounds in the procedure and interpretation of their mass and nuclear magnetic resonance spectroscopic behaviors.

  从胆甾-1，4-二烯-3-酮制备 1α-羟基胆固醇的程序被应用于 17，17-亚乙二氧基雄甾-1，4-二烯-3-酮和 20，20-亚乙二氧基孕甾-1，4-二烯-3-酮。本文所描述的成功结果为评估该程序在 3 氧甾体衍生物 1α 位引入羟基的广泛应用范围提供了依据。该过程包括三个步骤，从 3-酮-△1，4-类固醇开始：1）脱共轭为 3-酮-△1，5-类固醇；2）用金属酸酐还原为 3β-羟基-△1，5-类固醇；3）氢硼化为 1α，3β-二羟基-△5-类固醇。本文还包括在该过程中最终和中间化合物的明确鉴定，以及对其质量和核磁共振光谱行为的解释。
• Antiandrogens with marginal agonist activity and methods of use
  申请人：——

  公开号：US20040242618A1

  公开（公告）日：2004-12-02

  The instant invention provides potent antiandrogen compounds, such as 3&bgr;-acetoxyandrost-1,5-diene-17-ethylene ketal and 3&bgr;-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.

  本发明提供了强效抗雄激素化合物，例如3β-乙酰氧基雄烯-1,5-二烯-17-乙烯基甲醇和3β-羟基雄烯-1,5-二烯-17-乙烯基甲醇，并提供了它们在预防和治疗由雄激素受体介导的生物状况中的使用方法。因此，例如，本发明的化合物在预防和治疗前列腺癌中很有用。此外，发现本发明的化合物在预防和治疗雄激素非依赖性癌症，例如雄激素非依赖性前列腺癌中很有用。最后，本发明的化合物可用于治疗抗雄激素引起的戒断综合征。
• Prostate Cancer Treatment
  申请人：Lardy A. Henry

  公开号：US20080070881A1

  公开（公告）日：2008-03-20

  The instant invention provides potent antiandrogen compounds, such as 3β-acetoxyandrost-1,5-diene-17-ethylene ketal and 3β-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.

  本发明提供了强效的抗雄激素化合物，例如3β-乙酰氧基雄烯-1,5-二烯-17-乙烯基酮和3β-羟基雄烯-1,5-二烯-17-乙烯基酮，以及它们在预防和治疗由雄激素受体介导的生物状况中的使用方法。因此，例如，本发明的化合物对于预防和治疗前列腺癌非常有用。此外，发现本发明的化合物对于预防和治疗雄激素非依赖性癌症，例如雄激素非依赖性前列腺癌，也非常有用。最后，本发明的化合物可用于治疗抗雄激素引起的戒断综合征。
• Compounds and Formulations
  申请人：Lardy A. Henry

  公开号：US20080004250A1

  公开（公告）日：2008-01-03

  The instant invention provides potent antiandrogen compounds, such as 3β-acetoxyandrost-1,5-diene-17-ethylene ketal and 3β-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.

  本发明提供了有效的抗雄激素化合物，例如3β-乙酰氧基雄烯-1,5-二烯-17-乙烯基醚和3β-羟基雄烯-1,5-二烯-17-乙烯基醚，及其在预防和治疗由雄激素受体介导的生物状况中的应用方法。例如，本发明的化合物在预防和治疗前列腺癌方面非常有用。此外，已经发现本发明的化合物在预防和治疗雄激素非依赖性癌症，如雄激素非依赖性前列腺癌方面非常有用。最后，本发明的化合物可用于治疗抗雄激素诱导的戒断综合症。
• Steroids having 1,8-unsaturation and formulations comprising same
  申请人：Hollis-Eden Pharmaceuticals, Inc.

  公开号：US07514420B2

  公开（公告）日：2009-04-07

  The instant invention provides potent antiandrogen compounds, such as 3β-acetoxyandrost-1,5-diene-17-ethylene ketal and 3β-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.

  该发明提供了强效的抗雄激素化合物，例如3β-乙酰氧基雄烯-1,5-二烯-17-乙烯基醚和3β-羟基雄烯-1,5-二烯-17-乙烯基醚，以及它们在预防和治疗由雄激素受体介导的生物状况中的应用方法。因此，例如，该发明的化合物在预防和治疗前列腺癌方面是有用的。此外，已经发现该发明的化合物在预防和治疗雄激素非依赖性癌症，如雄激素非依赖性前列腺癌方面是有用的。最后，该发明的化合物可以用于治疗抗雄激素诱导的戒断综合症。