3,15α-dihydroxy-1,3,5(10)-estratrien-17-one | 2208-13-1

• 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: 3,15α-dihydroxy-1,3,5(10)-estratrien-17-one
• 英文别名: 15α-Hydroxy-oestron；15alpha-Hydroxyestrone；(8R,9S,13S,14S,15S)-3,15-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 2208-13-1
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: FDFNTZDUOBCJMD-DMHIMHRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 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：

  3,15α-dihydroxy-1,3,5(10)-estratrien-17-one 在 sodium tetrahydroborate 作用下， 生成 1,3,5(10)-雌甾三烯-3,15-alpha,17-beta-三醇
  参考文献：
  名称：

  Microbial Hydroxylation of Estrone and Estradiol in the 6β-, 7α-, and 15α-Positions

  摘要：

  DOI：

  10.1021/jo01029a014
• 作为产物：
  描述：

  3-Hydroxy-15α-acetoxy-oestra-1,3,5(10)-trien-17-on 在 盐酸 作用下， 以 丙酮 为溶剂， 生成 3,15α-dihydroxy-1,3,5(10)-estratrien-17-one
  参考文献：
  名称：

  Syntheses of 15α-Hydroxyestrone and 15α-Hydroxyestradiol

  摘要：

  通过新的合成路线，我们从雌酮中制备出了标题化合物（1、2）。用二硼烷对 14、15 或 15、16-双键进行氢硼化合，然后用碱性过氧化氢对有机硼烷进行氧化，很容易在 15α 位上引入羟基。在制备 1 的过程中，为了保护 3、17β-羟基，方便地使用了二甲基叔丁基硅烷官能团。

  DOI：

  10.1248/cpb.23.3141

文献信息

• Microbial hydroxylation of 17β-estradiol by <i>Penicillium brevicompactum</i>
  作者：Lihong Shan、Yang Li、Yanjie Chen、Minghui Yin、Jiajia Huang、Zhenzhong Zhang、Xiufang Shi、Hongmin Liu

  DOI：10.1080/10242422.2016.1247816

  日期：2016.7.3

  Abstract Microbial hydroxylation of 17β-estradiol (1) with Penicillium brevicompactum, a fungal species not used in biotransformation so far, yielded four metabolites: 1, 3, 5-estratriene-3, 15α-diol-17-one (2); 1, 3, 5-estratriene-3, 6α, 17β-triol (3); 1, 3, 5-estratriene-3, 15α, 17β-triol (4); and 1, 3, 5-estratriene-3, 6α, 15α-triol-17-one (5). All the products were determined by 1H NMR, 13C NMR

  摘要 17β-雌二醇 (1) 与 Penicillium brevicompactum（一种迄今为止未用于生物转化的真菌物种）的微生物羟基化产生了四种代谢物：1, 3, 5-estratriene-3, 15α-diol-17-one (2)；1, 3, 5-estratriene-3, 6α, 17β-triol (3); 1, 3, 5-estratriene-3, 15α, 17β-triol (4); 和 1, 3, 5-estratriene-3, 6α, 15α-triol-17-one (5)。所有产物均通过1H NMR、13C NMR、二维NMR和HRMS技术测定。化合物3、4、5是首次通过微生物转化报道，5是目前已知的新化合物。还提出了 17β-雌二醇通过短青霉的可能代谢途径。
• 16-Hydroxyestratrienes as selectively active estrogens
  申请人：Kuenzer Hermann

  公开号：US20060270845A1

  公开（公告）日：2006-11-30

  The invention describes new compounds as pharmaceutical active ingredients, which have in vitro a higher affinity to estrogen receptor preparations from rat prostates than to estrogen receptor preparations from rat uteri and in vivo a preferential action on bone rather than the uterus, their production, their therapeutic use and pharmaceutical dispensing forms that contain the new compounds. The new compounds are 16α- and 16β-hydroxy-estra-1,3,5(10)-estratrienes, which carry additional substituents on the steroid skeleton and can have one or more additional double bonds in the B-, C- and/or D-rings.

  本发明描述了新的化合物作为药物活性成分，这些化合物在体外与来自大鼠前列腺的雌激素受体制备物相比，对来自大鼠子宫的雌激素受体制备物具有更高的亲和力，在体内对骨骼具有优先作用而不是子宫，以及它们的生产、治疗用途和含有新化合物的制药分配形式。新的化合物是16α-和16β-羟基-雌-1,3,5（10）-三烯醇，其在类固醇骨架上携带额外的取代基，并且可以在B、C和/或D环中具有一个或多个额外的双键。
• SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMS) AND USES THEREOF
  申请人：Zhi Lin

  公开号：US20100256129A1

  公开（公告）日：2010-10-07

  Provided herein are compounds of formulae I to II that bind to androgen receptors and/or modulate activity of androgen receptors; and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

  本文提供了公式I到II的化合物，这些化合物能够结合到雄激素受体并/或调节雄激素受体的活性；以及制备和使用这些化合物的方法。还提供了包括这些化合物的组合物以及制备和使用这些组合物的方法。
• Selective androgen receptor modulators (SARMs) and uses thereof
  申请人：Ligand Pharmaceuticals Incorporated

  公开号：US20130184206A1

  公开（公告）日：2013-07-18

  Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors. Also provided are methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

  本文提供了与雄激素受体结合和/或调节雄激素受体活性的化合物。还提供了制备和使用这些化合物的方法。此外，还提供了包括这些化合物的组合物以及制备和使用这些组合物的方法。
• Characterization of the Oxidative Metabolites of 17β-Estradiol and Estrone Formed by 15 Selectively Expressed Human Cytochrome P450 Isoforms
  作者：Anthony J. Lee、May Xiaoxin Cai、Paul E. Thomas、Allan H. Conney、Bao Ting Zhu

  DOI：10.1210/en.2003-0192

  日期：2003.8.1

  We systematically characterized the oxidative metabolites of 17β-estradiol and estrone formed by 15 human cytochrome P450 (CYP) isoforms. CYP1A1 had high activity for 17β-estradiol 2-hydroxylation, followed by 15α-, 6α-, 4-, and 7α-hydroxylation. However, when estrone was the substrate, CYP1A1 formed more 4-hydroxyestrone than 15α- or 6α-hydroxyestrone, with 2-hydroxyestrone as the major metabolite. CYP1A2 had the highest activity for the 2-hydroxylation of both 17β-estradiol and estrone, although it also had considerable activity for their 4-hydroxylation (9–13% of 2-hydroxylation). CYP1B1 mainly catalyzed the formation of catechol estrogens, with 4-hydroxyestrogens predominant. CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 each showed a varying degree of low catalytic activity for estrogen 2-hydroxylation, whereas CYP2C18 and CYP2E1 did not show any detectable estrogen-hydroxylating activity. CYP3A4 had strong activity for the formation of 2-hydroxyestradiol, followed by 4-hydroxyestradiol and an unknown polar metabolite, and small amounts of 16α- and 16β-hydroxyestrogens were also formed. The ratio of 4- to 2-hydroxylation of 17β-estradiol or estrone with CYP3A4 was 0.22 or 0.51, respectively. CYP3A5 had similar catalytic activity for the formation of 2- and 4- hydroxyestrogens. Notably, CYP3A5 had an unusually high ratio of 4- to 2-hydroxylation of 17β-estradiol or estrone (0.53 or 1.26, respectively). CYP3A4 and 3A5 also catalyzed the formation of nonpolar estrogen metabolite peaks (chromatographically less polar than estrone). CYP3A7 had a distinct catalytic activity for the 16α-hydroxylation of estrone, but not 17β-estradiol. CYP4A11 had little catalytic activity for the metabolism of 17β-estradiol and estrone. In conclusion, many human CYP isoforms are involved in the oxidative metabolism of 17β-estradiol and estrone, with a varying degree of catalytic activity and distinct regioselectivity.

  22-0.51)。