3,17β-bis(benzyloxy)-2-methoxyestra-1,3,5(10)-triene | 159143-76-7

• 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: 3,17β-bis(benzyloxy)-2-methoxyestra-1,3,5(10)-triene
• 英文别名: 2-methoxy-β-estradiol dibenzyl ether；(8R,9S,13S,14S,17S)-2-methoxy-13-methyl-3,17-bis(phenylmethoxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene
• CAS: 159143-76-7
• 化学式: C₃₃H₃₈O₃
• 分子量: 482.663
• InChiKey: DFIFWOBSZFHZDZ-KGZARSPRSA-N

物化性质

• 沸点：
  600.4±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,17β-bis(benzyloxy)-2-methoxyestra-1,3,5(10)-triene 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 以11.5 mg的产率得到2-甲氧基雌二醇
  参考文献：
  名称：

  Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site

  摘要：

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.

  DOI：

  10.1021/jm00012a003
• 作为产物：
  描述：

  2-formylestradiol 在 四丁基碘化铵 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.17h， 生成 3,17β-bis(benzyloxy)-2-methoxyestra-1,3,5(10)-triene
  参考文献：
  名称：

  Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogs of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite of Estradiol That Inhibits Tubulin Polymerization by Binding to the Colchicine Binding Site

  摘要：

  In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 8-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors;of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.

  DOI：

  10.1021/jm00012a003

文献信息

• Estradiol conjugates and uses thereof
  申请人：The University of Melbourne

  公开号：US07037907B1

  公开（公告）日：2006-05-02

  A conjugated prodrug of an estradiol compound conjugated to a biological activity modifying agent.

  一个醚雌二醇化合物的共轭前药，与生物活性调节剂结合。
• EP1226154A4
  申请人：——

  公开号：EP1226154A4

  公开（公告）日：2005-03-23
• ESTRADIOL CONJUGATES AND USES THEREOF
  申请人：THE UNIVERSITY OF MELBOURNE

  公开号：EP1226154A1

  公开（公告）日：2002-07-31
• US7037907B1
  申请人：——

  公开号：US7037907B1

  公开（公告）日：2006-05-02
• [EN] ESTRADIOL CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUES D'ESTRADIOL ET LEURS UTILISATIONS
  申请人：UNIV MELBOURNE

  公开号：WO2001027132A1

  公开（公告）日：2001-04-19

  A conjugated prodrug of an estradiol compound conjugated to a biological activity modifying agent.