2-methylsulfanyl estradiol | 401479-54-7

• 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-methylsulfanyl estradiol
• 英文别名: (8R,9S,13S,14S,17S)-13-methyl-2-methylsulfanyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS: 401479-54-7
• 化学式: C₁₉H₂₆O₂S
• 分子量: 318.48
• InChiKey: MKWGPHYWMHVOQR-SSTWWWIQSA-N

物化性质

• 熔点：
  163-164 °C(Solv: ethanol (64-17-5))
• 沸点：
  461.4±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  65.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methylsulfanyl estradiol 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 3.0h， 以60%的产率得到2-methylsulfanylestradiol 3,17-O,O-bis-sulfamate
  参考文献：
  名称：

  2-Substituted Estradiol Bis-sulfamates, Multitargeted Antitumor Agents:  Synthesis, In Vitro SAR, Protein Crystallography, and In Vivo Activity

  摘要：

  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.

  DOI：

  10.1021/jm060705x
• 作为产物：
  描述：

  雌酚酮 在 盐酸 、 sodium tetrahydroborate 、 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 、 异丙醇 、 甲苯 为溶剂， 反应 48.25h， 生成 2-methylsulfanyl estradiol
  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

• 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.
• US7342004B2
  申请人：——

  公开号：US7342004B2

  公开（公告）日：2008-03-11
• [EN] 2-SUBSTITUTED ESTRADIOL DERIVATIVE FOR INHIBITING SUPEROXID DISMUTASE<br/>[FR] DERIVE D'ESTRADIOL 2-SUBSTITUE SERVANT A INHIBER SUPEROXYDE DISMUTASE
  申请人：STERIX LTD

  公开号：WO2002015910A1

  公开（公告）日：2002-02-28

  There is provided use of a compound in the manufacture o 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) wherein: X is a ring having at least 4 atoms in the ring; K is a hydrocarbyl group; R1 is a halogen group of the formula -L1-Z-R1', wherein L1 is an optional linker group, Z is O or S and R1' is a hydrocarbyl group or H; with the proviso that the compound is other than 2-methoxy-17β-oestradiol, 2-methoxyoestrone and 2-hydroxyestradiol.
• A-Ring-Substituted Estrogen-3-<i>O</i>-sulfamates:  Potent Multitargeted Anticancer Agents
  作者：Mathew P. Leese、Hatem A. M. Hejaz、Mary F. Mahon、Simon P. Newman、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm050066a

  日期：2005.8.1

  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.