androst-5-ene-3β,7α,17β-triol | 2226-66-6

• 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: androst-5-ene-3β,7α,17β-triol
• 英文别名: Androst-5-ene-3beta,7alpha,17beta-triol；(3S,7S,8R,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7,17-triol
• CAS: 2226-66-6
• 化学式: C₁₉H₃₀O₃
• 分子量: 306.445
• InChiKey: OEVZKEVBDIDVOI-FMKNUBLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3β,17β-dihydroxyandrost-5-en-7-one 在 potassium tri-sec-butyl-borohydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以58%的产率得到androst-5-ene-3β,7α,17β-triol
  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

• Hydroxylation of DHEA, androstenediol and epiandrosterone by Mortierella isabellina AM212. Evidence indicating that both constitutive and inducible hydroxylases catalyze 7α- as well as 7β-hydroxylations of 5-ene substrates
  作者：Teresa Kołek、Natalia Milecka、Alina Świzdor、Anna Panek、Agata Białońska

  DOI：10.1039/c1ob05350g

  日期：——

  underwent effective hydroxylation; 5-ene substrates – DHEA and androstenediol – were transformed into a mixture of 7α- and 7β- allyl alcohols, while epiandrosterone was converted into 7α- (mainly), 11α- and 9α- monohydroxy derivatives. Ketoconazole and cycloheximide inhibition studies suggest the presence of constitutive and substrate-induced hydroxylases in M. isabellina. On the basis of time course analysis

  DHEA的转型过程， 雄烯二醇 和 表雄甾酮在黄被孢霉AM212文化的影响。所提到的底物进行了有效的羟基化。5烯底物– DHEA和雄烯二醇 –被转化为7α-和7β-烯丙醇的混合物，而 表雄甾酮 被转化为7α-（主要是），11α-和9α-单羟基衍生物。 酮康唑和环己酰亚胺的抑制研究表明，伊萨贝拉霉中存在组成型和底物诱导的羟化酶。在时间过程的基础上分析脱氢表雄酮和雄烯二醇，烯丙基C中的氧化7 -H α和C 7 -H β键由相同的酶是一个合理的假设。
• Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids?
  作者：Natalia Milecka-Tronina、Teresa Kołek、Alina Świzdor、Anna Panek

  DOI：10.1016/j.bmc.2013.11.050

  日期：2014.1

  coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition

  在本文中，我们着重研究了Absidia coerulea AM93对DHEA，雄烯二醇，表雄甾酮和5α-雄烷-3,17-二酮进行7-羟基化的过程。除此之外，我们提出了对蓝藻中类固醇的羟基化的初步分析。AM93。DHEA和雄烯二醇被转化为烯丙基7-羟基衍生物的混合物，而EpiA和5α-雄烷-3,17-二酮主要转化为7α-和7β-醇，并伴有9α-和11α-羟基衍生物。基于（i）上述底物羟基化的时程分析，（ii）在不同pH下静息细胞的生物转化，（iii）酶抑制分析以及（iv）底物C–H键之间的几何关系经历羟基化和辅因子结合的活性氧原子，但假定相同的酶可催化氧化ç 7 -H α以及为C 7 -H β在-5-烯和5α二氢C键19-类固醇。在底物的结构和羟基化的区域选择性之间观察到的相关性表明，正常的结合酶-底物复合物中可能发生7β-羟基化，而在反向反向结合复合物中则发生7α-羟基化。
• Biotransformation of 3β-hydroxy-5-en-steroids by<i>Mucor silvaticus</i>
  作者：Yanjie Wang、Dongmei Sun、Zhibao Chen、Hongsheng Ruan、Wenzhong Ge

  DOI：10.3109/10242422.2013.813490

  日期：2013.8

  the examined substrates were transformed, mainly by 7α-hydroxylation. Studies carried out with M. silvaticus demonstrated the versatility of this organism in introducing hydroxyl groups at the 7α-, 9α-, 11α-, and 14α-positions in 3-ol-5-ene steroids. The relationships between the substrate structures and hydroxylated positions are also discussed.

  摘要 研究了 Mucor silvaticus 对 C-16 或/和 C-17 处具有不同取代基的四种 3β-羟基-5-en-类固醇的生物转化。通过 IR、MS、1H NMR、13C NMR 和 2-D NMR 对代谢物进行表征。所有检查的底物都被转化，主要是通过 7α-羟基化。对 M. silvaticus 进行的研究证明了这种生物在 3-ol-5-ene 类固醇的 7α-、9α-、11α-和 14α-位引入羟基的多功能性。还讨论了底物结构和羟基化位置之间的关系。
• 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。