3-(benzyloxy)-2-methoxyestra-1,3,5(10)-trien-17-one | 26357-07-3

• 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-(benzyloxy)-2-methoxyestra-1,3,5(10)-trien-17-one
• 英文别名: (8R,9S,13S,14S)-2-methoxy-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 26357-07-3
• 化学式: C₂₆H₃₀O₃
• 分子量: 390.522
• InChiKey: BIOBFFLKMVXKGI-JCISHKRCSA-N

物化性质

• 熔点：
  154-156 °C
• 沸点：
  536.6±50.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-2-methoxyestra-1,3,5(10)-trien-17-one 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 HDS02-182
  参考文献：
  名称：

  Novel and Potent 17β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors

  摘要：

  Structure-based drug design using the crystal structure of human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) led to the discovery of novel, selective, and the most potent inhibitors of 17 beta-HSD1 reported to date. Compounds 1 and 2 contain a side chain with an m-pyridylmethylamide functionality extended from the 16 beta position of a steroid scaffold. A mode of binding is proposed for these inhibitors, and 2 is a steroid-based 17 beta-HSD1 inhibitor with the potential for further development.

  DOI：

  10.1021/jm049045r
• 作为产物：
  描述：

  2-甲氧基雌二醇 在 aluminum isopropoxide 、 potassium carbonate 作用下， 以 环己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 39.0h， 生成 3-(benzyloxy)-2-methoxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Effects of Altering the Electronics of 2-Methoxyestradiol on Cell Proliferation, on Cytotoxicity in Human Cancer Cell Cultures, and on Tubulin Polymerization

  摘要：

  A series of new analogues of 2-methoxyestradiol (1) were synthesized to further elucidate the relationships between structure and activity. The compounds were designed to diminish the potential for metabolic deactivation at positions 2 and 17 and were analyzed as inhibitors of tubulin polymerization and for cytotoxicity. 17alpha-Methyl-beta-estradiol (30), 2-propynyl-17alpha-methylestradiol (39), 2-ethoxy-17-(1'-methylene)estra-1,3,5(10)-triene-3-ol (50) and 2-ethoxy-17alpha-methylestradiol (51) showed similar or greater tubulin polymerization inhibition than 2-methoxyestradiol (1) and contained moieties that are expected to inhibit deactivating metabolic processes. All of the compounds tested were cytotoxic in the panel of 55 human cancer cell cultures, and generally, the derivatives that displayed the most activity against tubulin were also the most cytotoxic.

  DOI：

  10.1021/jm049647a

文献信息

• SUBSTITUTED ESTRATRIENE DERIVATIVES AS 17BETA HSD INHIBITORS
  申请人：MESSINGER Josef

  公开号：US20080255075A1

  公开（公告）日：2008-10-16

  Substituted estratriene compounds of formula (I) useful in therapy, especially in the treatment or inhibition of a steroid hormone dependent disorder requiring the inhibition of a 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1, type 2 and/or type 3 enzyme, as well as their salts, pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  公式（I）中的替代雌三烯化合物在治疗中很有用，特别是在治疗或抑制需要抑制17β-羟基类固醇脱氢酶（17β-HSD）类型1、类型2和/或类型3酶的类固醇激素依赖性疾病方面，以及它们的盐、含有这种化合物的药物组合物和制备这种化合物的方法。
• [EN] OESTROGEN DERIVATIVES AS INHIBITORS OF STEROID SULPHATASE<br/>[FR] DERIVES ESTROGENES UTILISES EN TANT QU'INHIBITEURS DE STEROIDE SULFATASE
  申请人：STERIX LTD

  公开号：WO2004085459A1

  公开（公告）日：2004-10-07

  The present invention provides a compound comprising a steroidal ring system and an optional group R1 selected from any one of -OH, a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; wherein the D ring of the steroidal ring system is substituted by a group R2 of the formula -L-R3, wherein L is an optional linker group and R3 is selected from groups which are or which comprise one of a nitrite group, an alcohol, an ester, an ether, an amine and an alkene, provided that when R3 is or comprises an alcohol, L is present; and wherein the A ring of the steroidal ring system is substituted at position 2 or 4 with a group R4, wherein R4 is a hydrocarbyl group.

  本发明提供一种化合物，包括一种甾体环系统和一个可选的基团R1，所述基团R1从以下任一基团中选择：-OH、磺酸酯基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团；其中所述甾体环系统的D环通过一个公式-L-R3的基团R2取代，其中L是一个可选的连接基团，R3选择自一个亚硝酸盐基团、醇基团、酯基团、醚基团、胺基团和烯烃基团中的一个或组成一个，条件是当R3是或包含一个醇基团时，L存在；以及所述甾体环系统的A环在位置2或4处被一个基团R4取代，其中R4是一个烃基团。
• 17SS-HSD1 and STS inhibitors
  申请人：Messinger Josef

  公开号：US20060281710A1

  公开（公告）日：2006-12-14

  The present invention relates to novel substituted steroid derivatives which represent selectiv inhibitors of the 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and, in addition, which may represent inhibitors of the steroid sulphatase, as well as to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel substituted steroid derivatives, particularly their use in the treatment, inhibition, prophylaxis or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I and/or steroid sulphatase enzymes and/or requiring the lowering of the endogenous 17β-estradiol concentration.

  本发明涉及新型取代类固醇衍生物，这些衍生物代表17β-羟基类固醇脱氢酶I（17β-HSD1）的选择性抑制剂，此外，它们可能代表类固醇硫酸酶的抑制剂，以及它们的盐，含有这些化合物的药物制剂以及这些化合物的制备方法。此外，本发明涉及所述新型取代类固醇衍生物的治疗用途，特别是它们在治疗、抑制、预防或预防类固醇激素依赖性疾病或紊乱中的使用，例如需要抑制17β-羟基类固醇脱氢酶I和/或类固醇硫酸酶酶的依赖性疾病或紊乱，以及需要降低内源性17β-雌二醇浓度的疾病或紊乱。
• Synthesis, Antitubulin, and Antiproliferative SAR of Analogues of 2-Methoxyestradiol-3,17-<i>O</i>,<i>O</i>-bis-sulfamate
  作者：Fabrice Jourdan、Mathew P. Leese、Wolfgang Dohle、Ernest Hamel、Eric Ferrandis、Simon P. Newman、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm9018806

  日期：2010.4.8

  The synthesis and antiproliferative activity of analogues of estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent reveal that an H-bond acceptor is essential for high antiproliferative activity. The local environment in which this H-bond acceptor lies can be varied to an extent. The C-17-oxygen linker can be deleted or substituted with an electronically

  讨论了雌二醇3，17- O，O-双-氨基磺酸酯（E2bisMATEs）类似物的合成和抗增殖活性。C-17取代基的修饰表明，H键受体对于高抗增殖活性至关重要。该H键受体所处的局部环境可以在一定程度上变化。C-17-氧连接基可以被缺失或被电子中性的亚甲基取代，并且末端NH 2被甲基取代也是可接受的。甲磺酸酯10和14被证明与E2bisMATE 2和3等价，而砜20和35显示出增强的体外抗增殖活性。另外，首次建立了2-取代的雌二醇-3 - O-氨基磺酸衍生物作为微管蛋白聚合抑制剂的SAR 。这些试剂抑制放射性标记的秋水仙碱与微管蛋白的结合。
• Novel 2-alkoxyestradiol analogs with antiproliferative and antimitotic activity
  申请人：SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH

  公开号：US20030229061A1

  公开（公告）日：2003-12-11

  The application discloses novel 2-alkoxyestradiol analogs which exhibit anti-proliferative properties, and methods of making and using such compounds to inhibit undesired cell proliferation and tumor growth. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious disease wherein the infectious agent is particularly susceptible to inhibition by agents that disrupt microtubule organization and function.

  本发明披露了新型2-烷氧基雌二醇类似物，该类似物具有抗增殖特性，并公开了制备和使用这些化合物以抑制不良细胞增殖和肿瘤生长的方法。此外，还披露了治疗与不良血管生成和不良增殖有关的疾病的方法，以及治疗感染疾病的方法，其中感染剂特别易受到破坏微管组织和功能的药物抑制。