2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester | 1003855-51-3

• 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-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester
• 英文别名: (13S,17S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl phosphate；diethyl [(8R,9S,13S,14S,17S)-3-hydroxy-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] phosphate
• CAS: 1003855-51-3
• 化学式: C₂₃H₃₅O₆P
• 分子量: 438.501
• InChiKey: FZVDUMLLFNWHEX-JIAAILLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester 在 三甲基溴硅烷 、 甲醇 作用下， 以 氯仿 为溶剂， 反应 33.0h， 以92%的产率得到2-Methoxyestradiol 17-O-phosphate
  参考文献：
  名称：

  Synthesis and in Vivo Antitumor Evaluation of 2-Methoxyestradiol 3-Phosphate, 17-Phosphate, and 3,17-Diphosphate

  摘要：

  A prodrug strategy was investigated to address the problem of limited aqueous solubility and the resulting limited bioavailability of the antitumor agent 2-methoxyestradiol. The 3-phosphate, 17-phosphate, and 3,17-diphosphate of 2-methoxyestradiol were synthesized. 2-Methoxyestradiol 3-phosphate was metabolized more efficiently to the parent compound in vivo than 2-methoxyestradiol 17-phosphate, and it was also more cytotoxic in cancer cell cultures than either the 17-phosphate or the 3,17-diphosphate. These results agree with the in vivo anticancer activity of 2-methoxyestradiol 3-phosphate in a mouse Lewis lung carcinoma experimental metastasis model as opposed to the 17-phosphate and 3,17-diphosphate, both of which were inactive. The in vivo antitumor activity of 2-methoxyestradiol 3-phosphate at a dose of 200 mg/kg per day was comparable to that of a maximally tolerated dose of cyclophosphamide.

  DOI：

  10.1021/jm070639e
• 作为产物：
  描述：

  3-benzyloxy-2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 17.0h， 以96%的产率得到2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester
  参考文献：
  名称：

  Synthesis and in Vivo Antitumor Evaluation of 2-Methoxyestradiol 3-Phosphate, 17-Phosphate, and 3,17-Diphosphate

  摘要：

  A prodrug strategy was investigated to address the problem of limited aqueous solubility and the resulting limited bioavailability of the antitumor agent 2-methoxyestradiol. The 3-phosphate, 17-phosphate, and 3,17-diphosphate of 2-methoxyestradiol were synthesized. 2-Methoxyestradiol 3-phosphate was metabolized more efficiently to the parent compound in vivo than 2-methoxyestradiol 17-phosphate, and it was also more cytotoxic in cancer cell cultures than either the 17-phosphate or the 3,17-diphosphate. These results agree with the in vivo anticancer activity of 2-methoxyestradiol 3-phosphate in a mouse Lewis lung carcinoma experimental metastasis model as opposed to the 17-phosphate and 3,17-diphosphate, both of which were inactive. The in vivo antitumor activity of 2-methoxyestradiol 3-phosphate at a dose of 200 mg/kg per day was comparable to that of a maximally tolerated dose of cyclophosphamide.

  DOI：

  10.1021/jm070639e

文献信息

• Synthesis and in Vivo Antitumor Evaluation of 2-Methoxyestradiol 3-Phosphate, 17-Phosphate, and 3,17-Diphosphate
  作者：Allison B. Edsall、Gregory E. Agoston、Anthony M. Treston、Stacy M. Plum、Robert H. McClanahan、Tian-Sheng Lu、Wei Song、Mark Cushman

  DOI：10.1021/jm070639e

  日期：2007.12.27

  A prodrug strategy was investigated to address the problem of limited aqueous solubility and the resulting limited bioavailability of the antitumor agent 2-methoxyestradiol. The 3-phosphate, 17-phosphate, and 3,17-diphosphate of 2-methoxyestradiol were synthesized. 2-Methoxyestradiol 3-phosphate was metabolized more efficiently to the parent compound in vivo than 2-methoxyestradiol 17-phosphate, and it was also more cytotoxic in cancer cell cultures than either the 17-phosphate or the 3,17-diphosphate. These results agree with the in vivo anticancer activity of 2-methoxyestradiol 3-phosphate in a mouse Lewis lung carcinoma experimental metastasis model as opposed to the 17-phosphate and 3,17-diphosphate, both of which were inactive. The in vivo antitumor activity of 2-methoxyestradiol 3-phosphate at a dose of 200 mg/kg per day was comparable to that of a maximally tolerated dose of cyclophosphamide.