2-ethoxyestrone | 401479-55-8

• 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-ethoxyestrone
• 英文别名: 2-ethoxy-17-oxo-estra-1,3,5(10)-trien-3-ol；2-ethoxyestra-1,3,5(10)-trien-3-ol-17-one；(8R,9S,13S,14S)-2-ethoxy-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 401479-55-8
• 化学式: C₂₀H₂₆O₃
• 分子量: 314.425
• InChiKey: XWIVPDIKOGKSFF-IDLUEMFASA-N

物化性质

• 熔点：
  140-142 °C
• 沸点：
  474.4±45.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-ethoxyestrone 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 14.0h， 以83%的产率得到2-Ethoxyestradiol
  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
• 作为产物：
  描述：

  雌酮17-乙烯缩酮 在 盐酸 、 sodium hydroxide 、 disodium hydrogenphosphate 、 仲丁基锂 、 四丁基碘化铵 、 sodium hydride 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 59.0h， 生成 2-ethoxyestrone
  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

• Antiangiogenic agents
  申请人：Agoston E. Gregory

  公开号：US20050203075A1

  公开（公告）日：2005-09-15

  Compositions and methods for treating mammalian diseases or conditions characterized by undesirable angiogenesis by administering an effective amount of a compound of the formulae: wherein R a is selected from —OCH 3 , —OCH 2 CH 3 or —CCCH 3 ; and Z is selected from >C(H)—OH, >C(H)—O-alkyl, >C(H)—O-sulfamate, where alkyl is a linear, branched and/or cyclic hydrocarbon chain comprising 1 to 10 carbons.

  通过向哺乳动物疾病或状况中施用上述公式化合物的有效量来治疗其特征为不良血管生成的组合物和治疗方法： 其中 R a 从—OCH 3 ，—OCH 2 CH 3 或—CCCH 3 中选择；Z从>C(H)—OH，>C(H)—O-烷基，>C(H)—O-磺酸酯中选择，其中烷基是由1至10个碳组成的线性、支链和/或环烃链。
• (Arene)Cl2Ru(II) complexes with N-coordinated estrogen and androgen isonicotinates: Interaction with sex hormone binding globulin and anticancer activity
  作者：Rainer Schobert、Sebastian Seibt、Katharina Effenberger-Neidnicht、Caroline Underhill、Bernhard Biersack、Geoffrey L. Hammond

  DOI：10.1016/j.steroids.2010.12.009

  日期：2011.3

  (Arene)dichloridoruthenium(II) complexes with N-coordinated isonicotinates of androgens (6) and estrogens (9) were prepared and tested for affinity to the estrogen receptor (ER alpha) and sex hormone binding globulin (SHBG), as well as for cytotoxicity in cancer cells. None of the new complexes bound noticeably to the ER and most of them also bound less strongly to SHBG than the corresponding unmetallated steroids 7. In MTT assays the Ru(p-cymene) complexes 9 of 2-substituted estrones were equally or even more cytotoxic than the metal-free steroids against hormone-dependent (MCF-7 breast and KB-V1 cervix carcinomas) and hormone-independent (518A2 melanoma) cells. The addition of external SHBG to MU assays lowered the cytotoxicities of the complexes 9 and distinctly more so those of some steroids 7, probably by the way of sequestration and reduction of the cellular uptake. In the absence of SHBG the estrogen complexes 9 were internalized by 518A2 melanoma cells and ruthenated their DNA as quantified by ICP-OES. They also ruthenated salmon sperm DNA but did not change the topology of plasmid DNA in EMSA experiments. In addition, the Ru(p-cymene) complex of 2-ethoxyestrone (9c) was shown to reduce the motility of 518A2 melanoma cells in a wound-healing assay. (C) 2010 Elsevier Inc. All rights reserved.

  (arene)二氯化二钌(II)复合物与N-配位的雄激素（6）和雌激素（9）的异烟酸酰胺衍生物已被制备，并测试了其对雌激素受体（ERα）和性激素结合球蛋白（SHBG）的亲和力以及在癌细胞中的细胞毒性。新的复合物均未明显结合ER，且其中大多数与SHBG的结合力亦弱于相应的无金属甾体（7）。在MTT实验中，2-取代雌酮的Ru(p-甲乙基环己二烯)复合物（9）对激素依赖性（MCF-7乳腺癌和KB-V1宫颈癌）及激素非依赖性（518A2黑色素瘤）细胞的毒性与金属无甾体相当甚至更高。在加入外源性SHBG至HU实验中，其对复合物9的细胞毒性有所降低，且对某些甾体（7）的降低明显，可能是通过屏蔽及减少胞内摄取的途径实现。在无SHBG的情况下，雌激素复合物9被518A2黑色素瘤细胞摄入，并以ICP-OES定量其DNA的钌化修饰。它们亦能钌化鲑鱼精子DNA，但在EMSA实验中未改变质粒DNA的拓扑结构。此外，2-乙氧雌酮的Ru(p-甲乙基环己二烯)复合物（9c）在划痕修复实验中被证实可显著降低518A2黑色素瘤细胞的迁移能力。（C）2010 Elsevier Inc. 保留所有权利。
• Estradiol derivatives
  申请人：Agoston E. Gregory

  公开号：US20070135400A1

  公开（公告）日：2007-06-14

  Compositions and methods for treating mammalian disease characterized by undesirable angiogenesis by administering compounds of the general formula: wherein the variables are defined in the specification.

  本发明提供了一种通过给予下述通式化合物治疗恶性血管生成的哺乳动物疾病的组合物和方法：其中变量在规范中定义。
• Methods of treating disease states using antiangiogenic agents
  申请人：Agoston E. Gregory

  公开号：US20070010505A1

  公开（公告）日：2007-01-11

  Compositions and methods for treating mammalian disease characterized by undesirable angiogenesis by administering compounds of the general formula: wherein the variables are defined in the specification.

  通过给予一般公式中的化合物治疗由不良血管生成特征的哺乳动物疾病的组合物和方法：其中变量在规范中定义。
• Antitumor wirksame 2-alkoxyestradiolsulfamate
  申请人：Schering AG

  公开号：US20030100544A1

  公开（公告）日：2003-05-29

  The present invention relates to the use of 2-alkoxyestrogen sulfamates of general formula I 1 wherein R 1 and R 2 independently represent H, methyl, C 1 -C 4 acyl, benzoyl R 3 represents C 1 -C 4 alkyl or a group of formula C n F m H o , wherein n=1, 2, 3, 4, 5 or 6, m>1, and m+o=2n+1, R 4 and R 5 in each case represent H or, together, a methylene group or an additional double bond, R 6 represents H. R 7 represents OH, OC 1 -C 4 -alkyl, OC 1 -C 11 -acyl or OSO 2 NR 1 R 2 , the dashed lines in the B and C rings of the steroid skeleton additionally representing up to two double bonds, for the production of a medical drug for the treatment of tumor diseases which can be affected positively by inhibiting the tubulin polymerization. The inventive compounds are distinguished by the 2-alkoxy substitution in conjunction with the 17-hydroxy substitution. They have a special effect with regard to inhibiting tubulin polymerization and can be used, for example, for the treatment of prostate cancers.

  本发明涉及使用一般式I1中的2-烷氧基雌激素磺酸酯，其中R1和R2独立地表示H、甲基、C1-C4酰基、苯甲酰基，R3表示C1-C4烷基或公式CnFmHo的基团，其中n=1、2、3、4、5或6，m>1，且m+o=2n+1，R4和R5分别表示H或一起表示亚甲基基团或额外的双键，R6表示H，R7表示OH、OC1-C4烷基、OC1-C11酰基或OSO2NR1R2，类固醇骨架的B和C环中的虚线还可以表示多达两个双键，用于制备治疗肿瘤疾病的药物，该药物可以通过抑制微管聚合而产生积极影响。本发明的化合物具有2-烷氧基取代与17-羟基取代的特殊效果，可以用于治疗前列腺癌等疾病。