3-benzyloxy-2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester | 1003855-50-2

• 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: 3-benzyloxy-2-dimethoxy-β-estradiol-17-phosphoric acid diethyl ester
• 英文别名: diethyl [(8R,9S,13S,14S,17S)-2-methoxy-13-methyl-3-phenylmethoxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] phosphate
• CAS: 1003855-50-2
• 化学式: C₃₀H₄₁O₆P
• 分子量: 528.626
• InChiKey: MJIMTSMMPIZUEW-ZKVCXLDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  氯磷酸二乙酯 、 2-methoxy-3-benzyloxyestra-1,3,5 (10)-triene-17β-ol 在 titanium(IV) tetrabutoxide 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以89%的产率得到3-benzyloxy-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.