11β-(2-hydroxyethyl)-estradiol-3,17β-bis(benzyl ether) | 126559-84-0

• 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: 11β-(2-hydroxyethyl)-estradiol-3,17β-bis(benzyl ether)
• 英文别名: 3,17-dibenzyl,11β-(2')-hydroxy ethyl estradiol；11β-(2-hydroxyethyl)estra-1,3,5(10)-triene-3,17β-diol 3,17-bis(benzyl ether)；2-(3,17β-dibenzyloxyestra-1,3,5(10)-trien-11β-yl)ethanol；3,17β-dibenzyloxy-11β-(2'-hydroxyethyl)estra-1,3,5(10)-triene；11β-(2-hydroxy)ethyl-3,17-dibenzyl estradiol；2-[(8S,9S,11R,13S,14S,17S)-13-methyl-3,17-bis(phenylmethoxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-11-yl]ethanol
• CAS: 126559-84-0
• 化学式: C₃₄H₄₀O₃
• 分子量: 496.69
• InChiKey: NQMWSPPJGSEUHN-KVHLUJKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  11β-(2-hydroxyethyl)-estradiol-3,17β-bis(benzyl ether) 在 吡啶 作用下， 以 二甲基亚砜 为溶剂， 反应 145.5h， 生成 3-(3,17β-dibenzyloxyestra-1,3,5(10)-trien-11β-yl)propanenitrile
  参考文献：
  名称：

  Nonpolar and Short Side Chain Groups at C-11β of Estradiol Result in Antiestrogens

  摘要：

  We have previously found that esters of 11beta-estradiol carboxylates are transformed from an estrogen into an antiestrogen when the 11beta-side chain is increased in length from four to five non-hydrogen atoms (n greater than or equal to 5). To understand the structural requirements for this transformation and obtain metabolically stable analogues that are not susceptible to esterase cleavage, we have synthesized other compounds having an 11beta-side chain composed of other functional groups: ketones, amides, ethers, and thiono esters. With the exception of amides, which bind poorly to the estrogen receptor (ER), all of these compounds exhibit antiestrogenic action when the side chain length is n greater than or equal to 5. Ethers (n greater than or equal to 5), studied in more detail, inhibit the action of estradiol with either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak agonists and decrease the concentration of cholesterol in blood (an hepatic estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics of selective estrogen receptor modulators.

  DOI：

  10.1021/jm049352x
• 作为产物：
  描述：

  11β-(1-ethenyl)estra-1,3,5(10)-triene-3,17β-diol 3,17-bis(benzyl ether) 在 sodium hydroxide 、 dimethyl sulfide borane 、 双氧水 作用下， 生成 11β-(2-hydroxyethyl)-estradiol-3,17β-bis(benzyl ether)
  参考文献：
  名称：

  新型11β-取代的estra-1,3,5（10）-三烯-3,17β-二醇的合成与雌激素受体结合。

  摘要：

  作为开发用于核医学的雌激素放射性配体的计划的一部分，进行了一项研究，以研究取代基对假定放射化学物质的受体亲和力的影响。在这项研究中，设计了一种针对11β-（氟乙基）取代基引入的合成策略。通过五步程序从11β-乙烯基雌酮3-乙酸酯（4）开始以五步法制备目标化合物9，总产率为43％。通过X射线晶体学确定了11个β-乙烯基部分的立体化学。评价了最终产物和几种类似物，即11β-乙基-，-乙烯基-和（羟乙基）雌二醇（11、5和12）的雌激素受体结合亲和力。结果表明目标化合物和几种11个β-取代的类似物的相对结合亲和力大于雌二醇及其16个α-氟化衍生物。制备目标化合物9的方式适合与18F结合使用。

  DOI：

  10.1021/jm00174a010

文献信息

• 11beta-short chain substituted estradiol analogs and their use in the treatment of menopausal symptoms and estrogen sensitive cancer
  申请人：YALE UNIVERSITY

  公开号：US20040142915A1

  公开（公告）日：2004-07-22

  The present invention relates to novel 11-&bgr; estradiol ester compounds and their use as locally active estrogens in the treatment of the symptomology of menopause and to treat estrogen sensitive cancers, including breast cancer.

  本发明涉及新型11-β雌二醇酯化合物及其作为局部活性雌激素在治疗更年期症状和治疗雌激素敏感性癌症，包括乳腺癌中的用途。
• Selective nuclear receptor-targeted systems for delivery of cytotoxins to cancer cells for targeted photodynamic therapy
  申请人：——

  公开号：US20030220313A1

  公开（公告）日：2003-11-27

  An estrogen/antiestrogen-porphyrin conjugate, their composition and methods for their use are claimed. The active compounds of the invention are conjugates consisting of an estrogen or anti estrogen portion, tether or linker portion and a porphyrin portion. The method of invention exploits an active process that involves strong and specific interactions between nuclear receptor and its cognate ligand.

  一种雌激素/抗雌激素-卟啉共轭物、其组成和使用方法被声明。该发明的活性化合物是由雌激素或抗雌激素部分、连接或链节部分和卟啉部分构成的共轭物。该发明的方法利用一个涉及核受体及其同源配体之间强烈和特异相互作用的活性过程。
• Estradiol derivatives bearing sulfur-containing substituents at the 11β or 7α positions: versatile reagents for the preparation of estrogen conjugates
  作者：Daniela Spera、Gustavo Cabrera、Rita Fiaschi、Kathryn E Carlson、John A Katzenellenbogen、Elio Napolitano

  DOI：10.1016/j.bmc.2004.06.017

  日期：2004.8

  Estradiol derivatives bearing HS-, HSCH(2)-, HSCH(2)CH(2)-, MeS-, MeSCH(2)-, MeSCH(2)CH(2)-, or PhCH(2)SCH(2)CH(2)-groups at the 11beta position or an HS-group at the 7alpha position have been synthesized, and their binding affinity to the estrogen receptor (ER) determined. Nearly all of these substituted estrogens retain high binding affinity, and at the 11beta position, the sulfur atom has an effect

  带有HS-，HSCH（2）-，HSCH（2）CH（2）-，MeS-，MeSCH（2）-，MeSCH（2）CH（2）-或PhCH（2）SCH（2）的雌二醇衍生物已合成11beta位置的CH（2）-基或7alpha位置的HS-基，并确定了它们对雌激素受体（ER）的结合亲和力。几乎所有这些取代的雌激素都保持较高的结合亲和力，并且在11beta位置，硫原子对ER的结合作用类似于碳原子。这些硫醇衍生物是用于制备多种雌二醇缀合物的有前途的中间体。尤其是，甲基硫化物可能会发展成（11）C标记的药物，用于通过正电子发射断层显像对ER阳性肿瘤进行成像。
• Synthesis of 1,11β-ethanoestra-1,3,5(10)-triene-3,17β-diol: a novel bridged steroid derivative
  作者：Elio Napolitano、Rita Fiaschi、Robert Hanson

  DOI：10.1039/c39890001330

  日期：——

  The generation of an electrophilic centre on the 11β-(2-hydroxyethyl) estradiol 3,17β-bis(benzyl ether)(2) leads in two steps to the corresponding 1,11β-ethano-estradiol in a 61% overall yield.

  在11β-（2-羟乙基）雌二醇3,17β-双（苄基醚）（2）上形成亲电子中心，可分两个步骤生成相应的1,11β-乙-雌二醇，总产率为61％。
• Synthesis and estrogen receptor binding of novel 11.beta.-substituted estra-1,3,5(10)-triene-3,17.beta.-diols
  作者：Robert N. Hanson、Elio Napolitano、Rita Fiaschi、Kay D. Onan

  DOI：10.1021/jm00174a010

  日期：1990.12

  beta-vinyl moiety was established by X-ray crystallography. The final product and several analogues, 11 beta-ethyl-, -vinyl-, and (hydroxyethyl)estradiols (11, 5, and 12), were evaluated for their estrogen receptor binding affinity. The results indicate that the target compound and several 11 beta-substituted analogues possess relative binding affinities greater than of estradiol and its 16 alpha-fluorinated

  作为开发用于核医学的雌激素放射性配体的计划的一部分，进行了一项研究，以研究取代基对假定放射化学物质的受体亲和力的影响。在这项研究中，设计了一种针对11β-（氟乙基）取代基引入的合成策略。通过五步程序从11β-乙烯基雌酮3-乙酸酯（4）开始以五步法制备目标化合物9，总产率为43％。通过X射线晶体学确定了11个β-乙烯基部分的立体化学。评价了最终产物和几种类似物，即11β-乙基-，-乙烯基-和（羟乙基）雌二醇（11、5和12）的雌激素受体结合亲和力。结果表明目标化合物和几种11个β-取代的类似物的相对结合亲和力大于雌二醇及其16个α-氟化衍生物。制备目标化合物9的方式适合与18F结合使用。