(7R,8R,9S,13S,14S,17S)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3,7,17-三醇 | 3398-11-6

• 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
• 中文名称: (7R,8R,9S,13S,14S,17S)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3,7,17-三醇
• 英文名称: 7α-hydroxyestradiol
• 英文别名: estra-1,3,5(10)-triene-3,7α,17β-triol；Oestra-1,3,5(10)-trien-3,7α,17β-triol；estra-1,3,5(10)-triene-3β,7α,17β-triol；7α-hydroxy-β-estradiol；7α-hydroxy-estradiol；7alpha-Hydroxyestradiol；(7R,8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,7,17-triol
• CAS: 3398-11-6
• 化学式: C₁₈H₂₄O₃
• 分子量: 288.387
• InChiKey: CQPNIWHVQNCXHA-HTPGKPQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (7R,8R,9S,13S,14S,17S)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3,7,17-三醇 在 chromium(VI) oxide 作用下， 生成 3,7α-bis-benzoyloxy-estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Steroids. XCIX. Synthesis of Ring B Oxygenated Estrogens¹

  摘要：

  DOI：

  10.1021/ja01555a052
• 作为产物：
  描述：

  3,17β-diacetoxy-6α,7α-epoxy-estra-1,3,5(10)-triene 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 以85%的产率得到(7R,8R,9S,13S,14S,17S)-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-3,7,17-三醇
  参考文献：
  名称：

  Cytoprotective steroids (II)

  摘要：

  提供了一种治疗因中枢或外周神经系统细胞代谢妥协而需要治疗急性神经退行性的患者的方法，包括向该患者施用从雌二醇、去氢表雄酮和孕酮的7α-羟基衍生物中选择的一种7α-羟基取代类固醇的治疗有效量，以及其代谢前体。还提供了这些化合物用于制造药物和神经保护组合物的用途。

  公开号：

  US20030092692A1

文献信息

• Synthesis of 6- and 7-hydroxyestradiol 17-sulfates: the potential metabolites of estradiol 17-sulfate by female rat liver microsomes
  作者：Yoshimi Itoh、Noriko Matsuda、Kohji Harada、Kaori Takanashi、Kazuhiro Watanabe、Hidetoshi Takagi、Shinji Itoh、Itsuo Yoshizawa

  DOI：10.1016/s0039-128x(99)00011-2

  日期：1999.5

  The potential ring-B hydroxylated metabolites of estradiol 17-sulfate (1) by female rat liver microsomes were chemically prepared as authentic compounds. They are 6alpha- and 6beta-hydroxyestradiol 17-sulfates (7 and 9), and 7alpha- and 7beta-hydroxyestradiol 17-sulfates (12 and 16), whose synthetic procedures are described.

  雌性大鼠肝微粒体的雌二醇 17-硫酸酯 (1) 的潜在环 B 羟基化代谢物被化学制备为真实化合物。它们是 6alpha-和 6beta-hydroxyestradiol 17-sulfates（7 和 9），以及 7alpha-和 7beta-hydroxyestradiol 17-sulfates（12 和 16），它们的合成程序在描述中。
• Preparation of tritiated substituted estratrienes
  作者：A. D. Fraser、S. J. Clark、H. H. Wotiz

  DOI：10.1002/jlcr.2580120208

  日期：1976.4

  2,4-Dibromo-1,3,5(10)-estratriene-3,6β,17β-triol, 2,4-dibromo-1,3,5(10)-estratriene-3,7α,17β-triol and 2,4-dibromo-1,3,5(10)-estratriene-3,16β,17β-triol were prepared by bromination with N-bromosuccinimide. 2,4-Diiodo-1,3,5(10)-estratriene-3,7α,17β-triol, 2,4-diiodo-1,3,5 (10)-estratriene-3,11β,17β-triol and 2,4-diiodo-1,3,5(10)-estratriene-3, 16α-diol were formed by direct iodination with I2. Hydrogenolysis of the dihalo estrogen derivatives by tritium gas over 5% palladium/Al2O3 gave the 2,4-tritiated parent compounds in good yield with high specific activity.

  2,4-二溴-1,3,5(10)-雌甾三烯-3,6β,17β-三醇、2,4-二溴-1,3,5(10)-雌甾三烯-3,7α,17β-三醇和2,4-二溴-1,3,5(10)-雌甾三烯-3,16β,17β-三醇是通过N-溴代琥珀酰亚胺溴化制备的。2,4-二碘-1,3,5(10)-雌甾三烯-3,7α,17β-三醇、2,4-二碘-1,3,5 (10)-雌甾三烯-3,11β,17β-三醇和2,4-二碘-1,3,5(10)-雌甾三烯-3, 16α-二醇是通过I2直接碘化形成的。在5%钯/Al2O3上用氚气对二卤代雌激素衍生物进行氢解，可获得产率较高、比活性较高的2,4-氚化母体化合物。
• 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。
• 神経精神、免疫又は内分泌障害を治療するための７α置換ステロイドの使用
  申请人：——

  公开号：JP2000511404A

  公开（公告）日：2000-09-05

  \n (57)【要約】\n神経精神、免疫及び／又は内分泌障害の治療用又は認識増進の誘発用医薬組成物の製造における、コレステロール、アンドロステロン、プレグネノロンもしくはエストラジオールの炭素骨格をもつ７α−ヒドロキシもしくは７−オキソ置換３β−ヒドロキシステロイド又は７位及び３位の一方もしくは両方をエステルもしくはエーテル基で独立して置換したその類似体の使用を提供する。前記ステロイドの製造におけるＣｙｐ７ｂ酵素の使用と、種々の新規ステロイド並びに前記障害の診断用試験キット及び試験方法も提供する。\n

  7-羟基或 7-氧代 3β- 羟基类固醇或其类似物，其中一个或两个 7 位和 3 位独立地被酯基或醚基取代。还提供了Cyp7b酶在生产上述类固醇和各种新类固醇中的应用，以及诊断上述疾病的检测试剂盒和检测方法。\n