17α-(hydroxypropargyl)-3,17β-estradiol | 4140-25-4

• 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: 17α-(hydroxypropargyl)-3,17β-estradiol
• 英文别名: (8R,9S,13S,14S,17S)-17-(3-hydroxyprop-1-ynyl)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol
• CAS: 4140-25-4
• 化学式: C₂₁H₂₆O₃
• 分子量: 326.436
• InChiKey: KPQSURCKSFDYIS-MJCUULBUSA-N

物化性质

• 熔点：
  218-220 °C
• 沸点：
  540.6±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17α-(hydroxypropargyl)-3,17β-estradiol 在 四溴化碳 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以65%的产率得到17alpha-(Bromopropargyl)-3,17beta-estradiol
  参考文献：
  名称：

  Synthesis and biological evaluation of novel daunorubicin-estrogen conjugates

  摘要：

  The synthesis of two novel daunorubicin-estro-en conjugates with a steroidal and a non-steroidal ligand was undertaken in an attempt to target the cytotoxicity of anthracycline to estrogen-receptor positive cells. These conjugates (3 and 4), in contrast to their corresponding ligands, displayed weak binding affinities of 0.079 and 0.851 for the estrogen receptor. Conjugate 3 was consistently more cytotoxic than 4, which however showed some selectivity to estrogen receptor positive cell lines. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00110-6
• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.84h， 生成 17α-(hydroxypropargyl)-3,17β-estradiol
  参考文献：
  名称：

  Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone-Receptor Affinity of Several Organometallic Groups at the 17 Position

  摘要：

  In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17alpha position, modification of 17beta-estradiol at this position was carried out by using the organometallic groups -CdropC-(eta(5)-C5H4)RuCp, CH2-(eta(5)-C5H4)RuCp, -CdropC-(eta(5)-C5H4)-W(CO)(3)(Me), -(CdropCCHO)Co-2(CO)(6), and -(CdropCCH(2)OH)CO2(CO)(6). The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced. (RBA = 1%) for a substituent such as -CH2-(eta(5)-C5H4)-RuCp, in which the spacer is reduced to a single flexible sp(3) carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.

  DOI：

  10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m

文献信息

• Protein-Degrading Enediynes:  Library Screening of Bergman Cycloaromatization Products
  作者：Graham B. Jones、Justin M. Wright、George Hynd、Justin K. Wyatt、Molly Yancisin、Myles A. Brown

  DOI：10.1021/ol005926q

  日期：2000.6.1

  A screening method based on Bergman cycloaromatization products was applied to a compact library of estrogenic-enediyne hybrids, An enediyne candidate identified from the screen was subsequently synthesized, and it induced temperature- and concentration-dependent degradation of human estrogen receptor a upon cycloaromatization.
• High affinity 17α-substituted estradiol derivatives: Synthesis and evaluation of estrogen receptor agonist activity
  作者：Konstantinos M. Kasiotis、Christina Mendorou、Serkos A. Haroutounian、Michael N. Alexis

  DOI：10.1016/j.steroids.2005.10.004

  日期：2006.3

  We synthesized four derivatives of 17 beta-estradiol (E2) with an azide substitution on a 17 alpha-side chain of varying length, namely 17 alpha-(azidopropargyl)-3,17 beta-estradiol (5), its 17 beta-azido derivative (diazide 7), 17 alpha-(5-azido-pent-1-ynyl)-3,17 beta-estradiol (6) and 17 alpha-(azidopentyn-2-yl)-3,17 beta-estradiol (10). While most of the derivatives had low (7) or marginal (6 and 10) relative binding affinity (RBA) for both types of estrogen receptor (ER alpha and ER beta), the RBA alpha and RBAP of 5 were practically identical to those of E2. The estrogenic activity of the derivatives was assessed using estrogen-responsive breast (MCF-7) and endometrial cancer (Ishikawa) cells. While 5 was a potent and effective inducer of alkaline phosphatase in Ishikawa cells and 7 was less potent but as effective as 5,6 was marginally active and 10 was totally inactive in this respect. In the presence of 0.1 nM E2, however, 6 exhibited some ER antagonist activity at the highest concentration tested (1 mu M). Similar results were obtained as regards the potency and efficacy of stimulation of MCF-7 cell proliferation and induction of luciferase gene expression in MCF-7:D5L cells, a clone stably transfected with an estrogen-responsive form of the gene. These data suggest that, while 5, 6, 7 and 10 interact with either type of ER in isolation, only 5 and 7 exhibit substantial ER agonist activity in the different estrogen-target cells examined, which could provide for photoaffinity labelling of the receptor in the cell as well as in isolation. (c) 2005 Elsevier Inc. All rights reserved.
• Synthesis and biological evaluation of novel daunorubicin-estrogen conjugates
  作者：K Kasiotis

  DOI：10.1016/s0039-128x(01)00110-6

  日期：2001.10

  The synthesis of two novel daunorubicin-estro-en conjugates with a steroidal and a non-steroidal ligand was undertaken in an attempt to target the cytotoxicity of anthracycline to estrogen-receptor positive cells. These conjugates (3 and 4), in contrast to their corresponding ligands, displayed weak binding affinities of 0.079 and 0.851 for the estrogen receptor. Conjugate 3 was consistently more cytotoxic than 4, which however showed some selectivity to estrogen receptor positive cell lines. (C) 2001 Elsevier Science Inc. All rights reserved.
• Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone-Receptor Affinity of Several Organometallic Groups at the 17 Position
  作者：Siden Top、Hassane El Hafa、Anne Vessières、Michel Huché、Jacqueline Vaissermann、Gérard Jaouen

  DOI：10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m

  日期：2002.11.15

  In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17alpha position, modification of 17beta-estradiol at this position was carried out by using the organometallic groups -CdropC-(eta(5)-C5H4)RuCp, CH2-(eta(5)-C5H4)RuCp, -CdropC-(eta(5)-C5H4)-W(CO)(3)(Me), -(CdropCCHO)Co-2(CO)(6), and -(CdropCCH(2)OH)CO2(CO)(6). The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced. (RBA = 1%) for a substituent such as -CH2-(eta(5)-C5H4)-RuCp, in which the spacer is reduced to a single flexible sp(3) carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.