6Alpha-羟基雌酚酮 | 1476-78-4

• 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
• 中文名称: 6Alpha-羟基雌酚酮
• 英文名称: 6α-hydroxyestrone
• 英文别名: 6alpha-Hydroxyestrone；(6S,8R,9S,13S,14S)-3,6-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 1476-78-4
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: HTORTGVWUGQTHQ-WUAUYOTNSA-N

物化性质

• 沸点：
  492.1±45.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 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

ADMET

代谢

6alpha-羟基雌酮是雌酮的一个已知的人类代谢物。

6alpha-hydroxy-estrone is a known human metabolite of estrone.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  雌二醇 在 disodium hydrogenphosphate 、 potassium dihydrogenphosphate 、 葡萄糖 、 氧气 、 sodium chloride 、 calcium chloride 、 magnesium chloride 作用下， 反应 0.17h， 生成 雌酚酮 、 雌三醇 、 (7a)-3,7-二羟基-雌甾-1,3,5(10)-三烯-17-酮 、 6Alpha-羟基雌酚酮
  参考文献：
  名称：

  Identification of 6α- and 7α-hydroxyestrone as major metabolites of estrone and estradiol in porcine uterus.

  摘要：

  Polar metabolites extracted from the effluents of viable porcine uterine strips superfused with either 6,7-3H-estrone or 6,7-3H-estradiol were identified as a 1:1 mixture of 6 alpha-hydroxyestrone and 7 alpha-hydroxyestrone by paper chromatography in various systems, derivatization and crystallizations to a constant specific activity. The hydroxylated compounds are the only derivatives detected after estrone superfusion. The major metabolite of estradiol released in short-time experiments is estrone followed by its 6 alpha- and 7 alpha-hydroxylated derivatives.

  DOI：

  10.1016/0039-128x(83)90025-9

文献信息

• 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)。
• REMEDY FOR HORMONE-DEPENDENT CANCER
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP1568381A1

  公开（公告）日：2005-08-31

  A therapeutic agent for a hormone-dependent cancer, which comprises (a) a steroid-sulfatase inhibitor and (b) an agent for hormone therapy and/or an agent for chemotherapy, which may be administered together or separately at an interval, is provided. A method for treating a hormone-dependent cancer, which comprises administering (a) a steroid-sulfatase inhibitor and (b) an agent for hormone therapy and/or an agent for chemotherapy together or separately at an interval, is also provided. A steroid-sulfatase inhibitor which is used in combination with an agent for hormone therapy and/or an agent for chemotherapy, and which is administered together therewith or separately therefrom at an interval, is also provided. A kit for treating a hormone-dependent cancer, which comprises a first component comprising (a) a steroid-sulfatase inhibitor and a second component comprising (b) an agent for hormone therapy and/or an agent for chemotherapy, is also provided. A pharmaceutical composition, which comprises (a) a steroid-sulfatase inhibitor and (b) an agent for hormone therapy and/or an agent for chemotherapy, is also provided. Further, use of (a) a steroid-sulfatase inhibitor and (b) an agent for hormone therapy and/or an agent for chemotherapy for the manufacture of a therapeutic agent for a hormone-dependent cancer is provided.

  本发明提供了一种激素依赖性癌症的治疗剂，它包括(a)类固醇硫酸酯酶抑制剂和(b)激素治疗剂和/或化疗剂，这两种药物可以一起给药，也可以间隔一段时间分别给药。还提供了一种治疗激素依赖性癌症的方法，该方法包括(a)类固醇-硫酸酯酶抑制剂和(b)激素治疗制剂和/或化疗制剂，它们可以一起给药，也可以间隔一段时间分别给药。还提供了一种类固醇硫酸酯酶抑制剂，该抑制剂与激素治疗剂和/或化疗剂联合使用，并在一定间隔时间内一起或分开给药。还提供了一种用于治疗激素依赖性癌症的试剂盒，它包括由(a)类固醇硫酸酯酶抑制剂组成的第一组分和由(b)激素治疗剂和/或化疗剂组成的第二组分。还提供了一种药物组合物，它包含(a)类固醇硫酸酯酶抑制剂和(b)激素治疗剂和/或化疗剂。此外，还提供了使用(a)类固醇硫酸酯酶抑制剂和(b)激素治疗剂和/或化疗剂制造激素依赖性癌症治疗剂的方法。
• Methods for separation and detection of ketosteroids and other carbonyl-containing compounds
  申请人：Xu Xia

  公开号：US20050181514A1

  公开（公告）日：2005-08-18

  Methods for enhancing detection by mass spectroscopy (MS) and/or chromatographic separability of carbonyl-containing compounds such as steroids are disclosed. Reaction of a carbonyl compound with a sulfonhydrazide compound provides a sulfonhydrazone with enhanced ionization efficiency during the electrospray ionization process. In a particularly disclosed embodiment, derivatization of catechol estrogens with p-toluenesulfonhydrazide enhances both detection by atmospheric pressure ionization-MS (API-MS), such as electron spray ionization-MS (ESI-MS) and separation by liquid chromatography (such as HPLC) under reverse phase conditions. In yet other embodiments, the sulfonhydrazone is further reacted with a sulfonyl halide under alkaline conditions to derivatize hydroxyl groups in the compound. Prior formation of the sulfonhydrazide derivative protects the carbonyl bond of the compound during subsequent alkaline reaction with the sulfonyl halide.

  本发明公开了提高质谱（MS）检测能力和/或提高类固醇等含羰基化合物色谱分离能力的方法。在电喷雾电离过程中，羰基化合物与磺酰肼化合物反应生成的磺酰腙可提高电离效率。在一个特别公开的实施方案中，儿茶酚雌激素与对甲苯磺酸肼的衍生化既提高了大气压电离质谱（API-MS）（如电子喷雾电离质谱（ESI-MS））的检测能力，也提高了反相条件下液相色谱（如 HPLC）的分离能力。在另一些实施方案中，磺酰腙在碱性条件下与磺酰卤进一步反应，使化合物中的羟基衍生化。在随后与磺酰卤发生碱性反应时，事先形成的磺酰肼衍生物可保护化合物的羰基键。