2-ethylsulfanyl estrone | 401479-58-1

• 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-ethylsulfanyl estrone
• 英文别名: 2-sulfanylethylestrone；(8R,9S,13S,14S)-2-ethylsulfanyl-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 401479-58-1
• 化学式: C₂₀H₂₆O₂S
• 分子量: 330.491
• InChiKey: CCMAIFADJCJQDX-IDLUEMFASA-N

物化性质

• 熔点：
  139-141 °C(Solv: ethanol (64-17-5))
• 沸点：
  471.5±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 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：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-ethylsulfanyl estrone 在 sodium tetrahydroborate 、 2,6-二叔丁基-4-甲基吡啶 、 氨基磺酰氯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 0.25h， 生成 2-ethylsulfanyl estradiol 3-O-sulfamate
  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 32.25h， 生成 2-ethylsulfanyl 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

• (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。
• Thioether sulphamate steroids as steroid inhibtors and anti-cancer compounds
  申请人：——

  公开号：US20040009959A1

  公开（公告）日：2004-01-15

  There is provided use of a compound in the manufacture of a medicament to inhibit superoxide dismutase (SOD) or for use in the therapy of a condition or disease associated with SOD wherein the compound is of Formula I 1 wherein: X is a ring having at least 4 atoms in the ring; K is a hydrocarbyl group; R 1 is a halogen or a group of the formula -L 1 -Z-R 1 , wherein L 1 is an optional linker group, Z is O or S and R 1 is a hydrocarbyl group or H; with the proviso that the compound is other than 2-methoxy-17&bgr;-oestradiol, 2-methoxyoestrone and 2-hydroxyestradiol.

  提供了一种化合物在药物制造中的应用，用于抑制超氧化物歧化酶（SOD）或用于治疗与SOD相关的疾病或病症，其中该化合物的化学式为I1，其中：X是至少有4个原子的环；K是一个烃基；R1是卤素或公式-L1-Z-R1的基团，其中L1是可选的连接基团，Z是O或S，R1是烃基或氢；但该化合物不包括2-甲氧基-17β-雌二醇，2-甲氧基雌酮和2-羟基雌二醇。
• 2-Alkylsulfanyl estrogen derivatives: synthesis of a novel class of multi-targeted anti-tumour agents
  作者：Mathew P. Leese、Simon P. Newman、Atul Purohit、Michael J. Reed、Barry V.L. Potter

  DOI：10.1016/j.bmcl.2004.04.027

  日期：2004.6

  A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhanced anti-proliferative activity, combined with significant inhibition of steroid sulfatase, an enzyme target for the treatment of hormone-dependent tumours. (C) 2004 Elsevier Ltd. All rights reserved.
• THIOETHER-SULPHAMATE STEROIDS AS STEROID SULPHATASE INHIBITORS AND ANTI-CANCER COMPOUNDS
  申请人：Sterix Limited

  公开号：EP1311534A1

  公开（公告）日：2003-05-21
• US7342004B2
  申请人：——

  公开号：US7342004B2

  公开（公告）日：2008-03-11