11β-(4-(2-azidoethoxy)phenyl)-estra-1,3,5-(10)-trien-3,17β-diol | 1236153-22-2

• 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-(4-(2-azidoethoxy)phenyl)-estra-1,3,5-(10)-trien-3,17β-diol
• 英文别名: (8S,9R,11S,13S,14S,17S)-11-(4-(2-azidoethoxy)phenyl)-7,8,9,11,12,13,14,15,16,17-decahydro-13-methyl-6H-cyclopenta[a]phenanthrene-3,17-diol；(8S,9R,11S,13S,14S,17S)-11-[4-(2-azidoethoxy)phenyl]-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS: 1236153-22-2
• 化学式: C₂₆H₃₁N₃O₃
• 分子量: 433.55
• InChiKey: DKTBMEZPYNZNPX-NPSPJNBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  64
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11β-(4-(2-azidoethoxy)phenyl)-estra-1,3,5-(10)-trien-3,17β-diol 、 [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[5-[[4-[(2,2-difluorocyclooct-3-yn-1-yl)methyl]benzoyl]amino]pentylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate 在 copper(ll) sulfate pentahydrate sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 24.0h， 以50.5%的产率得到[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[5-[[4-[[1-[2-[4-[(8S,9R,11S,13S,14S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-11-yl]phenoxy]ethyl]-4,4-difluoro-6,7,8,9-tetrahydro-5H-cycloocta[d]triazol-5-yl]methyl]benzoyl]amino]pentylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
  参考文献：
  名称：

  [EN] STEROIDAL ANTI-HORMONE HYBRIDS
  [FR] HYBRIDES ANTI-HORMONAUX STÉROÏDIENS

  摘要：

  披露了新颖的化合物和组合物，用于抑制雄激素和雌激素受体信号传导，抑制雄激素信号传导的方法，抑制雌激素信号传导的方法，抑制共调节蛋白与雄激素或雌激素受体之间相互作用的方法，以及治疗癌症的方法。

  公开号：

  WO2010085747A1
• 作为产物：
  描述：

  (5alpha,10alpha)-5,10-环氧-雌甾-9(11)-烯-3,17-二酮环3-(1,2-乙二基缩醛) 在 sodium tetrahydroborate 、 sodium azide 、 乙酰溴 、 碘 、 caesium carbonate 、 magnesium 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 51.75h， 生成 11β-(4-(2-azidoethoxy)phenyl)-estra-1,3,5-(10)-trien-3,17β-diol
  参考文献：
  名称：

  Synthesis of a spin-labeled anti-estrogen as a dynamic motion probe for the estrogen receptor ligand binding domain

  摘要：

  The preparation and characterization of a novel nitroxide spin probe based on a steroidal anti-estrogen is described. The probe 5 demonstrated very high binding affinity for both the alpha and beta isoforms of the estrogen receptor-ligand binding domain. EPR spectrometric studies demonstrate conformational constraints for the ligand, consistent with the nitroxyl moiety occupying a position just beyond the receptor-solvent interface. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.091

文献信息

• Synthesis and evaluation of 11β-(4-Substituted phenyl) estradiol analogs: Transition from estrogen receptor agonists to antagonists
  作者：Robert N. Hanson、Edward Hua、J. Adam Hendricks、David Labaree、Richard B. Hochberg

  DOI：10.1016/j.bmc.2012.04.041

  日期：2012.6

  Introduction As part of our program to develop estrogen receptor (ER) targeted imaging and therapeutic agents we chose to evaluate 11β-substituted estradiol analogs as a representative scaffold. Previous synthetic studies provided an entry into this class of compounds and other work indicated that 11β-(substituted aryl) estradiol analogs were potent antagonists of the ER. Little information existed

  介绍 作为我们开发雌激素受体 (ER) 靶向成像和治疗剂计划的一部分，我们选择评估 11β 取代的雌二醇类似物作为代表性支架。先前的合成研究提供了此类化合物的入门资料，其他工作表明 11β-（取代芳基）雌二醇类似物是 ER 的有效拮抗剂。关于 11β-芳基雌二醇类似物从激动到拮抗转变所涉及的具体结构特征或其作为药物缀合支架的潜力的信息很少。 方法 我们使用现有合成方法的改进制备并表征了一系列 11β-（4-取代苯基）雌二醇类似物。新化合物以及标准类固醇激动剂和拮抗剂作为 ERβ-LBD 的竞争性配体进行了评估。功能测定使用石川细胞中碱性磷酸酶的诱导来确定化合物作为 ER 激动剂或拮抗剂的效力。 结果 该合成策略成功生成了一系列化合物，其中4-取代基依次从羟基修饰为甲氧基再修饰为叠氮基乙氧基/ N , N-二甲基氨基乙氧基，最终修饰为典型的含1,4-萘醌部分。这些新化合物均对 ERα-LBD
• STEROIDAL ANTI-HORMONE HYBRIDS
  申请人：Hanson Robert N.

  公开号：US20120046461A1

  公开（公告）日：2012-02-23

  Disclosed are novel compounds and compositions for inhibition of androgen and estrogen receptor signaling, methods for inhibiting androgen signaling, methods for inhibiting estrogen signaling, methods for inhibiting the interaction between a co-regulatory protein and an androgen or estrogen receptor, and methods for treating cancer.

  本发明涉及一种新型化合物和组合物，用于抑制雄激素和雌激素受体信号传导，抑制雄激素信号的方法，抑制雌激素信号的方法，抑制共同调节蛋白与雄激素或雌激素受体的相互作用的方法，以及用于治疗癌症的方法。
• Synthesis and preliminary evaluation steroidal antiestrogen–geldanamycin conjugates
  作者：J. Adam Hendricks、Robert N. Hanson、Michael Amolins、John M. Mihelcic、Brian S. Blagg

  DOI：10.1016/j.bmcl.2013.03.116

  日期：2013.6

  Three novel steroidal antiestrogen-geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11 beta-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity. (C) 2013 Published by Elsevier Ltd.
• [EN] STEROIDAL ANTI-HORMONE HYBRIDS<br/>[FR] HYBRIDES ANTI-HORMONAUX STÉROÏDIENS
  申请人：UNIV NORTHEASTERN

  公开号：WO2010085747A1

  公开（公告）日：2010-07-29

  Disclosed are novel compounds and compositions for inhibition of androgen and estrogen receptor signaling, methods for inhibiting androgen signaling, methods for inhibiting estrogen signaling, methods for inhibiting the interaction between a co-regulatory protein and an androgen or estrogen receptor, and methods for treating cancer.

  披露了新颖的化合物和组合物，用于抑制雄激素和雌激素受体信号传导，抑制雄激素信号传导的方法，抑制雌激素信号传导的方法，抑制共调节蛋白与雄激素或雌激素受体之间相互作用的方法，以及治疗癌症的方法。
• Synthesis of a spin-labeled anti-estrogen as a dynamic motion probe for the estrogen receptor ligand binding domain
  作者：J. Adam Hendricks、Stefano V. Gullà、David E. Budil、Robert N. Hanson

  DOI：10.1016/j.bmcl.2011.12.091

  日期：2012.2

  The preparation and characterization of a novel nitroxide spin probe based on a steroidal anti-estrogen is described. The probe 5 demonstrated very high binding affinity for both the alpha and beta isoforms of the estrogen receptor-ligand binding domain. EPR spectrometric studies demonstrate conformational constraints for the ligand, consistent with the nitroxyl moiety occupying a position just beyond the receptor-solvent interface. (C) 2012 Elsevier Ltd. All rights reserved.