17α-phenylestradiol | 128075-88-7

• 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: 17α-phenylestradiol
• 英文别名: 17alpha-Phenylestradiol；(8R,9S,13S,14S,17S)-13-methyl-17-phenyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
• CAS: 128075-88-7
• 化学式: C₂₄H₂₈O₂
• 分子量: 348.485
• InChiKey: VSIMDGDJOGYVHX-URYYLNOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 碘代三甲硅烷 作用下， 以 四氢呋喃 、 乙醚 、 苯 为溶剂， 反应 3.0h， 生成 17α-phenylestradiol
  参考文献：
  名称：

  Syntheses and affinities of novel organometallic-labeled estradiol derivatives: a structure-affinity relationship

  摘要：

  Two series of novel estradiol derivatives, including cationic species, labeled with organometallic fragments Cr(CO)3, Cp*Ru+, or Cp*Rh2+ [Cp* = eta-5-C5(CH3)5] either in the 17-alpha-position or on the A-ring were synthesized, and their relative binding affinities (RBA) for the estradiol receptor were determined. The Ru(II) and the Rh(III) cationic derivatives were obtained as stable salts with the following counter anions (BF4-, PF6-, CF3SO3-). The satisfactory RBA values obtained for most complexes belonging to the 17-alpha series confirm that this position tolerates the presence of bulky neutral species. For instance, complex 4, in which the organometallic fragment Cr(CO)3 Was attached to the phenyl ring of the 17-alpha-phenylethynyl fragment, exhibited an RBA value of 24%, very similar to that of the uncomplexed estrogen derivative 3. Surprisingly, the analogous cationic species 6 had no affinity for the estradiol receptor. This unprecedented result shows that the hormone binding site of the estrogen receptor does not tolerate the presence of a positive charge in the 17-alpha-position of the steroid. On the other hand, the alpha-face of the A-ring of estradiol did tolerate positively charged organometallic fragments bearing bulky substituents althoug the RBA value tended to decrease with increasing charge. The counterion in these cationic derivatives also affected binding affinity. For instance, the Ru(II) species 7a containing an CF3SO3- ion exhibited a reasonable RBA value (5.8%) compared to analogous species 13 with a PF6- ion (RBA of only 0.1%). Moreover, the triflate counteranion preserved the phenolic form of the A-ring of the estrogen derivative whereas the PF6- derivative was unstable and rapidly converted into the dienonylic form in buffer. The compared RBAs of the neutral and cationic species illustrate the preferences of the receptor hormone binding site in accepting or rejecting species of hydrophobic or hydrophilic character.

  DOI：

  10.1021/jm00095a006

文献信息

• 17α -Substituted analogs of estradiol for the development of fluorescent estrogen receptor ligands
  作者：Mohammad Salman、B.R. Reddy、Pete Delgado、Philip L. Stotter、Letitia C. Fulcher、Gary C. Chamness

  DOI：10.1016/0039-128x(91)90070-c

  日期：1991.7

  literature precedent and on our earlier work with small 17 alpha side chains. In this report, we describe syntheses and estrogen receptor binding affinities of 19 analogs of estradiol substituted in the 17 alpha position with larger side chains (of six to 11 carbons), some of which may be synthetically modified to link a fluorophore. These analogs were synthesized either by nucleophilic cleavage of estrone-17

  为了成功开发出高亲和力荧光团-雌二醇偶联物，荧光团必须连接到雌二醇分子上对其与受体结合干扰最小的位置。基于文献先例和我们早期使用小 17 α 侧链的工作，我们专注于 17 α 取代基作为荧光团连接的模型。在本报告中，我们描述了 19 种雌二醇类似物的合成和雌激素受体结合亲和力，它们在 17 α 位取代了较大的侧链（6 到 11 个碳），其中一些可能经过合成修饰以连接荧光团。这些类似物是通过雌酮-17 β-环氧乙烷 3-苄基醚的亲核裂解和随后的脱苄基（4 到 18），通过炔烃（21 到 24）的交叉偶联合成的，通过 17 α-乙炔雌二醇 3,17-双（四氢吡喃基醚）的烷基化和随后的酸性水解（25 至 28），或通过将雌酮与适当的芳基/炔基锂试剂（29、30 和 32）或与苄基溴化镁（ 31)。使用标准竞争测定法测定这些新合成的类似物对雌激素受体（大鼠子宫）的相对结合亲和力。结果表明，侧链中迁
• Structure−Activity Relationships of 17α-Derivatives of Estradiol as Inhibitors of Steroid Sulfatase
  作者：Roch P. Boivin、Van Luu-The、Roger Lachance、Fernand Labrie、Donald Poirier

  DOI：10.1021/jm0001166

  日期：2000.11.1

  inhibit steroid sulfatase activity may be a rewarding approach to the treatment of androgeno-sensitive and estrogeno-sensitive diseases. In the present study, we report the chemical synthesis and biological evaluation of a new family of steroid sulfatase inhibitors. The inhibitors were designed by adding an alkyl, a phenyl, a benzyl, or a benzyl substituted at position 17alpha of estradiol (E(2)), a C18-steroid

  类固醇硫酸酯酶或甾基硫酸酯酶是广泛分布在人体组织中的微粒体酶，其催化硫酸化的3-羟基类固醇水解为相应的游离活性3-羟基类固醇。由于雄激素和雌激素可能是从血液中可用的脱氢表雄酮硫酸盐（DHEAS）和硫酸雌酮（E（1）S）开始在癌细胞内合成的，因此使用抑制类固醇硫酸酯酶活性的治疗剂可能是一种有益的方法。雄激素敏感性和雌激素敏感性疾病的治疗。在本研究中，我们报告了甾族硫酸酯酶抑制剂新家族的化学合成和生物学评估。通过添加在C18类固醇的雌二醇（E（2））的17α位上取代的烷基，苯基，苄基或苄基来设计抑制剂 使用均质的JEG-3细胞或转染到HEK-293细胞中的类固醇硫酸酯酶进行酶分析。我们观察到，疏水取代基可强烈抑制类固醇硫酸酯酶，而亲水取代基则较弱。尽管在17α-位的疏水基团增加了抑制活性，但位阻因素却起到了相反的作用。如17alpha-decyl-E（2）和17alpha-dodecyl-E（
• 11.beta.-Substituted Estradiol Derivatives, Potential High-Affinity Carbon-11-Labeled Probes for the Estrogen Receptor: A Structure-Affinity Relationship Study
  作者：Elio Napolitano、Rita Fiaschi、Kathryn E. Carlson、John A. Katzenellenbogen

  DOI：10.1021/jm00003a005

  日期：1995.2

  In view of their possible development as carbon-11-labeled receptor-based radiotracers for imaging estrogen-responsive breast tumors, we have synthesized a series of estradiols (1), estriols (2), 11 beta-ethylestradiols (3), 11 beta-ethylestriols (4), 11 beta-methoxyestradiols (5), and 11 beta-methoxyestriols (6), differing in the type of substituent R present at the 17 alpha-position (a, -H; b, -CH3; c, -C=CH; d, -C=CCH3; e, -Ph; f, -CH=CHMe cis), and measured their binding affinity for the estrogen receptor relative to estradiol(RBA): As expected, all the derivatives having an 11 beta-ethyl substituent have good binding properties (3a-d, 4a-d, RBA (25 degrees C): 109-3000%), and among them there are several promising candidates for carbon-11 labeling. Moxestrol (RBA (25 degrees C) = 185%) and its corresponding estriol derivative (4c, RBA (25 degrees C) = 20%) were the analogs having the highest affinity in the 11 beta-methoxyestradiol (5a-f) and 11 beta-methoxyestriol (6a-e) series, respectively; other analogs (R = Me, C=CMe, Ph, or cis-CH=CHMe) had uniformly lower RBA values.
• Syntheses and affinities of novel organometallic-labeled estradiol derivatives: a structure-affinity relationship
  作者：Hani El Amouri、Anne Vessieres、Dominique Vichard、Siden Top、Michel Gruselle、Gerard Jaouen

  DOI：10.1021/jm00095a006

  日期：1992.8

  Two series of novel estradiol derivatives, including cationic species, labeled with organometallic fragments Cr(CO)3, Cp*Ru+, or Cp*Rh2+ [Cp* = eta-5-C5(CH3)5] either in the 17-alpha-position or on the A-ring were synthesized, and their relative binding affinities (RBA) for the estradiol receptor were determined. The Ru(II) and the Rh(III) cationic derivatives were obtained as stable salts with the following counter anions (BF4-, PF6-, CF3SO3-). The satisfactory RBA values obtained for most complexes belonging to the 17-alpha series confirm that this position tolerates the presence of bulky neutral species. For instance, complex 4, in which the organometallic fragment Cr(CO)3 Was attached to the phenyl ring of the 17-alpha-phenylethynyl fragment, exhibited an RBA value of 24%, very similar to that of the uncomplexed estrogen derivative 3. Surprisingly, the analogous cationic species 6 had no affinity for the estradiol receptor. This unprecedented result shows that the hormone binding site of the estrogen receptor does not tolerate the presence of a positive charge in the 17-alpha-position of the steroid. On the other hand, the alpha-face of the A-ring of estradiol did tolerate positively charged organometallic fragments bearing bulky substituents althoug the RBA value tended to decrease with increasing charge. The counterion in these cationic derivatives also affected binding affinity. For instance, the Ru(II) species 7a containing an CF3SO3- ion exhibited a reasonable RBA value (5.8%) compared to analogous species 13 with a PF6- ion (RBA of only 0.1%). Moreover, the triflate counteranion preserved the phenolic form of the A-ring of the estrogen derivative whereas the PF6- derivative was unstable and rapidly converted into the dienonylic form in buffer. The compared RBAs of the neutral and cationic species illustrate the preferences of the receptor hormone binding site in accepting or rejecting species of hydrophobic or hydrophilic character.