2-ethyl-estrone | 304681-53-6

• 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
• 英文名称: 2-ethyl-estrone
• 英文别名: 2-Ethylestrone；(8R,9S,13S,14S)-2-ethyl-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 304681-53-6
• 化学式: C₂₀H₂₆O₂
• 分子量: 298.425
• InChiKey: AQWFDYRHOGVKFU-MQJTVSLUSA-N

物化性质

• 熔点：
  208-210 °C(Solv: methanol (67-56-1))
• 沸点：
  459.7±45.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-ethyl-estrone 在 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 HDS02-098
  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：

  雌酚酮 在 盐酸 、 仲丁基锂 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 34.17h， 生成 2-ethyl-estrone
  参考文献：
  名称：

  A-Ring-Substituted Estrogen-3-O-sulfamates:  Potent Multitargeted Anticancer Agents

  摘要：

  Efficient and flexible syntheses of 2-substituted estrone, estradiol and their 3-O-sulfamate (EMATE) derivatives have been developed using directed ortho-lithiation methodology. 2-Substituted EMATEs display a similar antiproliferative activity profile to the corresponding estradiols against a range of human cancer cell lines. 2-Methoxy (3, 4), 2-methylsulfanyl (20, 21) and 2-ethyl EMATEs (32, 33) proved the most active compounds with 2-ethylestradiol-3-O-sulfamate (33), displaying a mean activity over the NCI 55 cell line panel 80-fold greater than the established anticancer agent 2-methoxyestradiol (2). 2-Ethylestradiol-3-O-sulfamate (33) was also an effective inhibitor of angiogenesis using three in vitro markers, and various 2-substituted EMATEs also proved to be inhibitors of steroid sulfatase (STS), a therapeutic target for the treatment of hormone-dependent breast cancer. The potential of this novel class of multimechanism anticancer agents was confirmed in vivo with good activity observed in the NCI hollow fiber assay and in a MDA-MB-435 xenograft mouse model.

  DOI：

  10.1021/jm050066a

文献信息

• Synthesis, molecular modeling and biological evaluation of potent analogs of 2-methoxyestradiol
  作者：Nora al-Kazaale、Phuong T. Tran、Farhad Haidari、Eirik Johansson Solum、Sandra Liekens、Peter Vervaeke、Ingebrigt Sylte、Jing-Jy Cheng、Anders Vik、Trond Vidar Hansen

  DOI：10.1016/j.steroids.2018.05.002

  日期：2018.8

  lead compound towards the development of new anti‐cancer drugs. Herein, the synthesis, molecular modeling, anti‐proliferative and anti‐angiogenic effects of ten 2‐ethyl and four 2‐methoxy analogs of estradiol are reported. The ethyl group was introduced to the steroid A‐ring using a novel Friedel‐Crafts alkylation protocol. Several analogs displayed potent anti‐proliferative activity with IC50‐values in

  图形抽象图。没有可用的字幕。亮点介绍了抗癌剂 2-甲氧基雌二醇的新 SAR 信息。通过区域选择性 Friedel-Crafts 反应制备的 2-乙基取代类似物。一些类似物显示出比 2-甲氧基雌二醇更有效的细胞毒性作用。我们的研究结果表明这些类似物没有在秋水仙碱结合位点结合。摘要 内源性类固醇 2-甲氧基雌二醇 (1) 作为开发新型抗癌药物的先导化合物引起了极大的兴趣。本文报道了雌二醇的 10 种 2-乙基和 4 种 2-甲氧基类似物的合成、分子建模、抗增殖和抗血管生成作用。使用新的 Friedel-Crafts 烷基化方案将乙基引入类固醇 A 环。几种类似物对 CEM 人白血病癌细胞系显示出有效的抗增殖活性，IC50 值在亚微摩尔范围内。因此，在这些细胞中，所有这些化合物都被证明比先导化合物 2-甲氧基雌二醇 (1) 更有活性。还使用体外管形成试验测试了六种最能抑制细胞生长的类似物作为抗血管生成剂。IC50
• 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。
• Structure–Activity Relationships of C-17 Cyano-Substituted Estratrienes as Anticancer Agents
  作者：Mathew P. Leese、Fabrice L. Jourdan、Keira Gaukroger、Mary F. Mahon、Simon P. Newman、Paul A. Foster、Chloe Stengel、Sandra Regis-Lydi、Eric Ferrandis、Anna Di Fiore、Giuseppina De Simone、Claudiu T. Supuran、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm701319c

  日期：2008.3.13

  vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also

  讨论了17-氰基2-取代的estra-1,3,5（10）-三烯作为抗癌剂的合成，SAR和临床前评价。2-甲氧基17β-氰基甲基estra-1,3,5（10）-三烯-3-醇（14），但没有相关的2-乙基衍生物7和相关的3-O-氨基磺酸盐8和15显示出有效的抗增殖作用（分别针对MCF-7 GI 50 300、60和70 nM）对人癌细胞的抗癌作用。对SAR的研究表明，连接C-17的空间不受阻碍的氢键受体很可能是增强活性的关键。化合物8显示出显着的体外抗血管生成活性，并证实了其充当微管破坏剂的能力。还观察到氨基磺酸酯衍生物对甾族硫酸酯酶和碳酸酐酶II（hCAII）的抑制活性，并通过蛋白质晶体学研究了15与hCAII之间的相互作用。在体内证实了这些多机制抗癌药的潜力，在无胸腺裸鼠MDA-MB-231人乳腺癌异种移植模型中观察到有前景的14和15活性。
• [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。
• New 2-substituted estra-1,3,5(10)-trien-17-ones as inhibitors of 17beta-hydroxy steroid dehydrogenase type 1
  申请人：Hillisch Alexander

  公开号：US20060009434A1

  公开（公告）日：2006-01-12

  The invention relates to new 2-substituted estra-1,3,5(10)-trien-17-ones of general formula I in which R 2 means a saturated or unsaturated C 1 -C 8 -alkyl group, a C 1 -C 5 -alkyloxy group, an aralkyl radical or alkylaryl radical, a radical —O—C n F m H o , whereby n=1, 2, 3, 4, 5 or 6, m≧1 and m+o=2n+1, or a group CH 2 XY, in which X stands for an oxygen atom and Y stands for an alkyl radical with 1 to 4 carbon atoms, as well as a halogen atom or a nitrile group, R 13 means a hydrogen atom or a methyl group, R 16 means a hydrogen atom or a fluorine atom, Z means an oxygen atom or a sulfur atom, R 3 and R 5 , in each case independently of one another, mean an α- or β-position hydrogen atom, R 4 and R 6 , in each case independently of one another, mean an α- or β-position hydrogen atom, a C 1 -C 5 -alkyl group, a C 1 -C 5 -alkyloxy group, a C 1 -C 5 -acyl group or a hydroxy group or an aralkyl radical or alkylaryl radical, R 3 and R 4 together mean an oxygen atom, R 5 and R 6 together mean an oxygen atom, R 7 and R 8 in each case mean a hydrogen atom or together a CH 2 group, as well as their pharmaceutically acceptable salts, their manufacture and use as medicaments for prophylaxis and therapy of estrogen-dependent diseases that can be influenced by the inhibition of 17β-hydroxy steroid dehydrogenase type 1.

  本发明涉及一般式I的新2-取代的酮类化合物，其中R2代表饱和或不饱和的C1-C8烷基基团，C1-C5烷氧基团，芳基烷基基团或烷基芳基基团，基团—O—CnFmHo，其中n=1、2、3、4、5或6，m≥1且m+o=2n+1，或基团CH2XY，其中X代表氧原子，Y代表具有1至4个碳原子的烷基基团，以及卤原子或腈基团，R13代表氢原子或甲基基团，R16代表氢原子或氟原子，Z代表氧原子或硫原子，R3和R5分别独立地表示α或β位的氢原子，R4和R6分别独立地表示α或β位的氢原子，C1-C5烷基基团，C1-C5烷氧基团，C1-C5酰基团，羟基或芳基烷基基团或烷基芳基基团，R3和R4一起表示氧原子，R5和R6一起表示氧原子，R7和R8分别表示氢原子或一起表示一个CH2基团，以及它们的药学上可接受的盐，它们的制备和用作预防和治疗由于17β-羟基类固醇脱氢酶类型1的抑制而可影响的雌激素依赖性疾病的药物。