3,17β-bis(benzyloxy)-11α-hydroxymethylestra-1,3,5(10)-triene | 534572-55-9

• 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)-11α-hydroxymethylestra-1,3,5(10)-triene
• 英文别名: 3,17β-dibenzyloxy-11β-hydroxymethylestra-1,3,5(10)-triene；[(8S,9R,11S,13S,14S,17S)-13-methyl-3,17-bis(phenylmethoxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-11-yl]methanol
• CAS: 534572-55-9
• 化学式: C₃₃H₃₈O₃
• 分子量: 482.663
• InChiKey: PKVLURJIOSVCPT-FEYUTSBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 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：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,17β-bis(benzyloxy)-11α-hydroxymethylestra-1,3,5(10)-triene 在 palladium on activated charcoal 氢气 、 potassium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 72.5h， 生成 11β-butoxymethylestra-1,3,5(10)-triene-3,17β-diol
  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：

  雌二醇 在 锂硼氢 、 草酰氯 、 sodium hydride 、 二甲基亚砜 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 儿萘酚硼烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 112.0h， 生成 3,17β-bis(benzyloxy)-11α-hydroxymethylestra-1,3,5(10)-triene
  参考文献：
  名称：

  Synthesis and evaluation of radioiodinated estrogens for diagnosis and therapy of male urogenital tumours

  摘要：

  我们发现了一种新的雌激素受体（ER）靶向配体，它具有皮摩尔亲和力，可作为放射性碘的载体。这种配体是治疗ER+男性肿瘤的潜在放射治疗药物。

  DOI：

  10.1039/d3ob00114h

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。
• Synthesis and Evaluation of B-, C-, and D-Ring-Substituted Estradiol Carboxylic Acid Esters as Locally Active Estrogens
  作者：David C. Labaree、Jing-xin Zhang、Heather A. Harris、Craig O'Connor、Toni Y. Reynolds、Richard B. Hochberg

  DOI：10.1021/jm0204340

  日期：2003.5.1

  great influence on hormonal activity and esterase hydrolysis. Formate esters at 7alpha and 15alpha were good estrogens, but lengthening the chain to acetate dramatically decreased hormonal activity. However, the 7alpha-formate esters were not enzymatically hydrolyzed. At 11beta, the acetate (methyl ester) was an effective estrogen, but increasing the chain length to propionate dramatically reduced hormonal

  我们合成了雌二醇的衍生物，这些衍生物经过结构修饰以用作“软”雌激素，并在人体的地理有限区域内发挥作用。没有全身作用的雌激素。我们以前已经显示了用16alpha取代的雌二醇类似物在类固醇环附近羧基化，既不与雌激素受体结合，也不激活雌激素反应性基因。但是，当羧酸被掩盖为酯时，它们会与受体结合并刺激雌激素反应。通过非特异性酯酶的酶促水解可以使这些雌激素失活，从而限制了它们的作用范围。在这里，我们描述了我们的持续研究，旨在通过在7α-，11β-，在甾体核中的15α-位和雌激素受体容纳大的取代基的位置。测试了这些化合物的雌激素受体结合（雌激素受体α和β），在培养的石川细胞中刺激雌激素敏感基因以及作为酶促水解的底物。在体内试验中测试了可能的候选药物的全身和局部雌激素作用。生物学研究表明，无论连接点如何，所有短链羧酸C-1至C-3均无激素作用，而许多酯则具有雌激素作用。类固醇核上的位点对激素活性和酯酶水
• 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。
• Nonpolar and Short Side Chain Groups at C-11β of Estradiol Result in Antiestrogens
  作者：Jing-xin Zhang、David C. Labaree、Richard B. Hochberg

  DOI：10.1021/jm049352x

  日期：2005.3.1

  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.
• Synthesis and evaluation of radioiodinated estrogens for diagnosis and therapy of male urogenital tumours
  作者：Feodor Braun、Marcel Jaschinski、Philipp Täger、Verena Marmann、Melanie von Brandenstein、Barbara Köditz、Thomas Fischer、Sergio Muñoz-Vázquez、Beate Zimmermanns、Markus Dietlein、Ferdinand Sudbrock、Phillip Krapf、Dietmar Fischer、Axel Heidenreich、Alexander Drzezga、Stefan Kirsch、Markus Pietsch、Klaus Schomäcker

  DOI：10.1039/d3ob00114h

  日期：——

  We identified a new estrogen receptor (ER)-targeting ligand with picomolar affinity serving as vehicle for radioiodines. This ligand is a potential radiotheranostics for ER⁺ male tumours.

  我们发现了一种新的雌激素受体（ER）靶向配体，它具有皮摩尔亲和力，可作为放射性碘的载体。这种配体是治疗ER+男性肿瘤的潜在放射治疗药物。