17-(3-hydroxy-1-methylpropyl)-3-(phenylmethoxy)-estra-1,3,5(10),16-tetraene | 533925-73-4

• 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: 17-(3-hydroxy-1-methylpropyl)-3-(phenylmethoxy)-estra-1,3,5(10),16-tetraene
• 英文别名: (20S)-3-(phenylmethoxy)-19,24-dinorchola-1,3,5(10),16-tetraen-23-ol；(3S)-3-[(8S,9S,13S,14S)-13-methyl-3-phenylmethoxy-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl]butan-1-ol
• CAS: 533925-73-4
• 化学式: C₂₉H₃₆O₂
• 分子量: 416.604
• InChiKey: ZJBMPCVIIKHAAP-KXZNEODKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17-(3-hydroxy-1-methylpropyl)-3-(phenylmethoxy)-estra-1,3,5(10),16-tetraene 在 烯丙基溴化镁 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 25.25h， 生成 (20S)-3-benzyloxy-19,26(27)-dinorchola-1,3,5(10),16,23E-pentaen-25-oic acid methyl ester
  参考文献：
  名称：

  Regio- and Stereoselective Ruthenium-Catalyzed Hydrovinylation of 1,3-Dienes:  Application to the Generation of a 20(S) Steroidal Side Chain

  摘要：

  The addition of ethylene to 1,3-dienes and 1-vinylcycloalkenes, catalyzed by two ruthenium complexes, proceeds in a regioselective fashion to afford 3-methyl-1,4-dienes as products. For a steroidal-based 1-vinylcycloalkene, the addition is stereospecific, giving a product with a 20(S) configuration.

  DOI：

  10.1021/ol030031+
• 作为产物：
  描述：

  17-(1-methyl-2-propenyl)-3-(phenylmethoxy)-estra-1,3,5(10),16-tetraene 在 氢氧化钾 、 双氧水 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 生成 17-(3-hydroxy-1-methylpropyl)-3-(phenylmethoxy)-estra-1,3,5(10),16-tetraene
  参考文献：
  名称：

  Regio- and Stereoselective Ruthenium-Catalyzed Hydrovinylation of 1,3-Dienes:  Application to the Generation of a 20(S) Steroidal Side Chain

  摘要：

  The addition of ethylene to 1,3-dienes and 1-vinylcycloalkenes, catalyzed by two ruthenium complexes, proceeds in a regioselective fashion to afford 3-methyl-1,4-dienes as products. For a steroidal-based 1-vinylcycloalkene, the addition is stereospecific, giving a product with a 20(S) configuration.

  DOI：

  10.1021/ol030031+

文献信息

• Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: A combined synthesis, binding and docking study
  作者：Christopher McCullough、Terrence S. Neumann、Jayapal Reddy Gone、Zhengjie He、Christian Herrild、Julie Wondergem (nee Lukesh)、Rajesh K. Pandey、William A. Donaldson、Daniel S. Sem

  DOI：10.1016/j.bmc.2013.11.024

  日期：2014.1

  Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds

  合成了各种雌激素类似物，并使用荧光偏振置换试验测试其与人 ERα 的结合。还使用对接计算预测了结合亲和力和方向。对接能够准确预测雌二醇的相对结合亲和力和方向，但前提是存在桥接 Arg394/Glu353 的紧密结合的水分子。二羟基化合物有时会以两个方向结合，这两个方向在其羟基的相对位置方面是相反的。预测二羟基化合物与其脂肪族羟基结合，与 ERα 中的 His524 相互作用。一种基于非甾体的二羟基化合物对 ERβ 的特异性是 ERα 的 1000 倍，并且对激动剂 ERβ 的特异性是拮抗剂活性的 25 倍。对接预测表明，这种特异性可能是由于脂肪族羟基与 ERβ 激动剂形式的 His475 与拮抗剂形式的 Thr299 的相互作用。但是，并非所有化合物都需要存在这种脂肪族羟基，因为单羟基（酚类）化合物通过与 ERα Arg394/Glu353/水三元组的羟基氢键相互作用以及范德华相互作用以高亲和力结合
• [EN] SUBSTITUTED (4'-HYDROXYPHENYL)CYCLOALKANE COMPOUNDS AND USES THEREOF AS SELECTIVE AGONISTS OF THE ESTROGEN RECEPTOR BETA ISOFORM<br/>[FR] COMPOSÉS SUBSTITUÉS DE (4'-HYDROXYPHENYL)CYCLOALKANE ET LEURS UTILISATIONS EN TANT QU'AGONISTES SÉLECTIFS DE L'ISOFORME BÊTA DU RÉCEPTEUR D'ŒSTROGÈNES
  申请人：UNIV MARQUETTE

  公开号：WO2015077611A1

  公开（公告）日：2015-05-28

  Disclosed are substituted (4'-hydroxylphenyl)cycloalkane compounds and there use as selective agonists of the estrogen receptor beta isoform (ΕΚβ). The disclosed compounds may be formulated as pharmaceutical compositions and administered to treat diseases associated with ERβ activity, such as proliferative diseases and disorders and/or psychiatric diseases or disorders.

  本文披露了替代的(4'-羟基苯基)环烷化合物及其作为雌激素受体β异构体（ERβ）的选择性激动剂的用途。所披露的化合物可以制成药物组合物，并用于治疗与ERβ活性相关的疾病，如增生性疾病和紊乱以及精神疾病或紊乱。
• Substituted (4'-hydroxyphenyl)cyclohexane compounds and uses thereof as selective agonists of the estrogen receptor beta isoform
  申请人：Marquette University

  公开号：US10570077B2

  公开（公告）日：2020-02-25

  Disclosed are substituted (4′-hydroxylphenyl)cycloalkane compounds and there use as selective agonists of the estrogen receptor beta isoform (ERβ). The disclosed compounds may be formulated as pharmaceutical compositions and administered to treat diseases associated with ER activity, such as proliferative diseases and disorders and/or psychiatric diseases or disorders.

  公开了取代的（4′-羟基苯基）环烷烃化合物及其作为雌激素受体β异构体（ERβ）选择性激动剂的用途。所公开的化合物可配制成药物组合物，用于治疗与ER活性相关的疾病，如增殖性疾病和紊乱和/或精神疾病或紊乱。
• Ligand Tuning in Asymmetric Hydrovinylation of 1,3-Dienes: A Stereoselective Route to Either Steroid-C₂₀ (<i>S</i>) or -C₂₀ (<i>R</i>) Derivatives
  作者：Biswajit Saha、Craig R. Smith、T. V. RajanBabu

  DOI：10.1021/ja711475f

  日期：2008.7.1

  1,3-Dienes derived from steroidal D-ring C(17)-ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2- or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands, it is possible to synthesize either the C(20) (R)- or (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Because the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.
• SUBSTITUTED (4'-HYDROXYPHENYL)CYCLOAKLKANE COMPOUNDS AND USES THEREOF AS SELECTIVE AGONISTS OF THE ESTROGEN RECEPTOR BETA ISOFORM
  申请人：Marquette University

  公开号：US20160340279A1

  公开（公告）日：2016-11-24

  Disclosed are substituted (4′-hydroxylphenyl)cycloalkane compounds and there use as selective agonists of the estrogen receptor beta isoform (ERβ). The disclosed compounds may be formulated as pharmaceutical compositions and administered to treat diseases associated with ER activity, such as proliferative diseases and disorders and/or psychiatric diseases or disorders.