2-hydroxy-3,17β-bis(benzyloxy)estra-1,3,5(10)-triene | 159143-75-6

• 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-3,17β-bis(benzyloxy)estra-1,3,5(10)-triene
• 英文别名: 3,17β-bis(benzyloxy)-2-hydroxyestra-1,3,5(10)-triene；2-hydroxy-3,17β-O,O-bis(benzyloxy)estradiol；2-Hydroxy-3,17β-Dibenzyloxyestra-1,3,5(10)-Triene；2-hydroxy-β-estradiol dibenzyl ether；2-Hydroxy-3,17beta-Dibenzyloxyestra-1,3,5(10)-Triene；(8R,9S,13S,14S,17S)-13-methyl-3,17-bis(phenylmethoxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-2-ol
• CAS: 159143-75-6
• 化学式: C₃₂H₃₆O₃
• 分子量: 468.636
• InChiKey: UCWZBOTVXCXDFN-OVVCPANJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxy-3,17β-bis(benzyloxy)estra-1,3,5(10)-triene 在 palladium on activated charcoal 氢气 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成 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：

  雌二醇 在 盐酸 、 水 、 仲丁基锂 、 四丁基碘化铵 、 sodium hydride 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-hydroxy-3,17β-bis(benzyloxy)estra-1,3,5(10)-triene
  参考文献：
  名称：

  合成 2-[11C] 甲氧基-3,17β-O,O-双（氨磺酰基）雌二醇作为一种新的潜在 PET 试剂，用于在癌症中对类固醇硫酸酯酶 (STS) 进行成像

  摘要：

  类固醇硫酸酯酶 (STS) 催化类固醇硫酸盐水解为雌酮，雌酮是肿瘤中雌激素的主要来源。碳酸酐酶 II (CAII) 通过氨基磺酸部分的单阴离子形式与酶活性位点中的锌原子配位而在红细胞中高表达，并且 CAII 在多种肿瘤中高表达。2-Methoxy-3,17β-O,O-双（氨磺酰基）雌二醇 (5) 是一种双功能 STS-CAII 抑制剂，可选择性地抑制 STS，其 IC(50) 值为 39 nMIC(50)，而 CAII 值为 379 nMIC(50) . 该化合物在 NCI 60 细胞系面板中表现出强大的抗增殖活性，平均图中点值为 87 nM，在早期 Lewis 肺模型中也具有体外和体内抗血管生成活性。该化合物最近已被开发为多靶点抗癌剂。STS 和 CAII 在癌症中都过表达，并已成为癌症治疗和癌症分子成像的有吸引力的靶标。在这里，我们报告了 2-[(11)C] 甲氧基-3,17β-O,O

  DOI：

  10.1016/j.steroids.2012.04.007

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。
• Synthesis of 2-alkoxyestradiols
  申请人：Pharm-Eco Laboratories, Inc.

  公开号：US06051726A1

  公开（公告）日：2000-04-18

  Disclosed is a method of preparing a compound represented by the following structural formula: ##STR1## The method comprises reacting bromine (Br.sub.2) and an aliphatic organic acid with a compound represented by the following structural formula: ##STR2## R.sub.1 and R.sub.2 are each independently a hydroxyl protecting group.

  本发明揭示了一种制备下列结构式所代表的化合物的方法：##STR1## 该方法包括将溴（Br.sub.2）和脂肪族有机酸与下列结构式所代表的化合物反应：##STR2## 其中R.sub.1和R.sub.2各自独立地是羟基保护基。
• Synthesis of Analogs of 2-Methoxyestradiol with Enhanced Inhibitory Effects on Tubulin Polymerization and Cancer Cell Growth
  作者：Mark Cushman、Hu-Ming He、John A. Katzenellenbogen、Ravi K. Varma、Ernest Hamel、Chii M. Lin、Siya Ram、Yesh P. Sachdeva

  DOI：10.1021/jm9700833

  日期：1997.7.1

  A new series of estradiol analogs was synthesized in an attempt to improve on the anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of tubulin polymerization and the binding of [H-3]colchicine to tubulin, as well as for in vitro cytotoxicity in human cancer cell cultures. Overall, the most potent of the new compounds were 2-(2',2',2'-trifluoroethoxy)-6-oximinoestradiol, 2-ethoxy-6-oximinoestradiol, and 2-ethoxy-6-methoximinoestradiol. These agents lacked significant affinity for the estrogen receptor. The cytotoxicities of the compounds correlated in general with their abilities to inhibit tubulin polymerization, thus supporting inhibition of tubulin polymerization as the primary mechanism causing inhibition of cell growth.
• 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