estradiol 3,17β-disulphamate

• 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: estradiol 3,17β-disulphamate
• 英文别名: estradiol 3,17β-disulfamate；estradiol 3,17-O,O-bis-sulfamate；STX49；3,17β-disulfamoyloxy-13β-methyl-1,3,5(10)-gonatriene；[(8R,9S,13S,14S,17S)-13-methyl-3-sulfamoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] sulfamate
• 化学式: C₁₈H₂₆N₂O₆S₂
• 分子量: 430.546
• InChiKey: ZVSCPWTWOPVEDW-ZBRFXRBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  雌二醇 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 16.0h， 生成 estradiol 3,17β-disulphamate
  参考文献：
  名称：

  3,17-二取代的2-烷基-1,3,5（10）-三烯-3-醇衍生物：合成，体外和体内抗癌活性。

  摘要：

  雌二醇3,17-O，O-双-氨基磺酸盐抑制类固醇硫酸酯酶（STS），碳酸酐酶（CA），并在被C-2取代时抑制癌细胞的增殖和血管生成。探索了C-2取代和17-氨基磺酸雌二醇-3,17-O，O-双-氨基磺酸盐的替代方法，并开发了有效而实用的合成方法。对人类癌细胞系的评估显示，2-甲基衍生物27（DU145 GI（50）= 0.38 microM）是最活跃的新型双氨基磺酸盐，而2-乙基-17-氨基甲酸酯衍生物52（GI（50）= 0.22 microM） ）被证明是其系列中最活跃的（参见2-ethylestradiol-3,17-O，O-bis-sulfamate 4 GI（50）= 0.21 microM）。较大的C-2取代基对活性有害。X射线晶体学研究了2-甲氧基17-氨基甲酸酯50，与母体双氨基磺酸酯3相比，作为STS抑制剂的出奇地弱13倍。使用乳腺癌和前列腺癌异种移植物证实了4作为口服抗

  DOI：

  10.1021/jm070405v

文献信息

• Steroid sulfamates, method for the production and use thereof
  申请人：id pharma GmbH

  公开号：US06339079B1

  公开（公告）日：2002-01-15

  A novel class of gonane type and D-homo-gonane type steroids having sulfatase-inhibiting and/or estrogenic activity is presented for application in the pharmaceutical industry. The number and location of sulfamoyloxy groups on the steroids provides for sulfatase inhibiting and estrogenic activities that independently vary over a wide range, allowing the customization of the pharmaceutical for specific purposes, including treatment and diagnosis of estrogen-dependent tumors.

  提出了一种新型的戈南型和D-同型戈南型类固醇，具有抑制磺酸酯酶和/或雌激素活性，可应用于制药行业。类固醇上磺酰氧基团的数量和位置提供了磺酸酯酶抑制和雌激素活性，可独立地在广泛范围内变化，允许为特定目的定制药物，包括治疗和诊断雌激素依赖性肿瘤。
• Estra-1,3,5(10)-trien derivatives, processes for their preparation and
  申请人：Jenapharm GmbH & Co. KG

  公开号：US06080735A1

  公开（公告）日：2000-06-27

  This invention is relating to new estra-1,3,5(10)-trien-sulfamates carrying at the 3-position an R--SO.sub.2 --O--group, with R being an R.sup.1 R.sup.2 N--group in which R.sup.1 and R.sup.2, independently of each other, represent a hydrogen atom, an alkyl residue with 1-5 C atoms or, together with the N atom, a polymethylene-imino residue with 4-6 C atoms or a morpholino residue. The compounds, according to this invention, are suitable for hormonal contraception and climacteric hormone replacement therapy (HRT) as well as for treatment of gynecological and andrological diseases. Hence, only low hepatic estrogenicity is exhibited by the compounds according to this invention. Also described are processes for preparation of the compounds according to this invention and for preparation of pharmaceutical compositions.

  本发明涉及新的以3位带有R-SO2-O基团的Estra-1,3,5（10）-三烯基磺酸盐，其中R是R1R2N基团，其中R1和R2独立地表示氢原子，具有1-5个碳原子的烷基残基，或者与N原子一起表示具有4-6个碳原子的聚亚甲基亚胺残基或吗啡环残基。根据本发明，这些化合物适用于激素避孕和更年期激素替代疗法（HRT）以及妇科和男科疾病的治疗。因此，这些化合物仅表现出低肝雌激素作用。还描述了根据本发明制备这些化合物和制备制药组合物的过程。
• Steroidsulfamate, Verfahren zu ihrer Herstellung und Anwendung derselben
  申请人：Sterix Limited

  公开号：EP1772462A2

  公开（公告）日：2007-04-11

  The invention relates to novel estratrienes of general formula (I) containing several sulfamoyoxy groups per molecule (m = 1-5). They are produced by reacting the appropriate steroid alcohols with sulfamoy or n-alkyl or alkanoylsulfamoyl chloride in the presence of a buffer or a base. The compounds of formula (I) an characterized by a high sulfatase activity and are therefore suitable for the treatment of diseases responding to sulfatase inhibition. The high target specificity of the inventive compounds in relation to sulfatase and estrogen transcription assays enable said compounds, which are provided with a radiolabel e.g. [18F] fluorine instead of F. to be used as potential markers in tumor diagnosis.

  本发明涉及通式(I)的新型雌三烯，每个分子含有多个氨基磺酰基（m = 1-5）。它们是由适当的甾醇与氨基磺酰基或正烷基或烷酰氨基磺酰氯在缓冲液或碱的存在下反应生成的。式（I）化合物的特点是具有较高的硫酸酯酶活性，因此适用于治疗对硫酸酯酶抑制有反应的疾病。本发明化合物在硫酸酯酶和雌激素转录检测方面具有高度靶向特异性，可作为肿瘤诊断中的潜在标记物。
• 2-Substituted Estradiol Bis-sulfamates, Multitargeted Antitumor Agents:  Synthesis, In Vitro SAR, Protein Crystallography, and In Vivo Activity
  作者：Mathew P. Leese、Bertrand Leblond、Andrew Smith、Simon P. Newman、Anna Di Fiore、Giuseppina De Simone、Claudiu T. Supuran、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm060705x

  日期：2006.12.1

  The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.
• Roemer; Steinbach; Kasch, Advanced Synthesis and Catalysis, 1999, vol. 341, # 6, p. 574 - 583
  作者：Roemer、Steinbach、Kasch、Scheller

  DOI：——

  日期：——