2-hydroxy-3-O-methoxymethyl-17,17-ethylenedioxyestrone | 874920-40-8

• 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-hydroxy-3-O-methoxymethyl-17,17-ethylenedioxyestrone
• 英文别名: (8'R,9'S,13'S,14'S)-3'-(methoxymethoxy)-13'-methylspiro[1,3-dioxolane-2,17'-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene]-2'-ol
• CAS: 874920-40-8
• 化学式: C₂₂H₃₀O₅
• 分子量: 374.477
• InChiKey: QZQMADZMUNYSER-HPNQWNLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-hydroxy-3-O-methoxymethyl-17,17-ethylenedioxyestrone 在 盐酸 、 sodium tetrahydroborate 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 89.0h， 生成 2-甲氧基雌二醇
  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 sodium hydroxide 、 disodium hydrogenphosphate 、 仲丁基锂 、 sodium hydride 、 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 22.0h， 生成 2-hydroxy-3-O-methoxymethyl-17,17-ethylenedioxyestrone
  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

• 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.