5-hydroxy-6-(4-hydroxyphenyl)-1-phenyl-hexan-3-one | 1158956-62-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-hydroxy-6-(4-hydroxyphenyl)-1-phenyl-hexan-3-one
• 英文别名: 5-Hydroxy-6-(4-hydroxyphenyl)-1-phenylhexan-3-one
• CAS: 1158956-62-7
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: MVRWWRLEWTZBMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-(4-hydroxy-benzyl)-3-phenethyl-4,5-dihydro-isoxazole 在 水 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以99%的产率得到5-hydroxy-6-(4-hydroxyphenyl)-1-phenyl-hexan-3-one
  参考文献：
  名称：

  Synthesis and biological evaluation of phenolic 4,5-dihydroisoxazoles and 3-hydroxy ketones as estrogen receptor α and β agonists

  摘要：

  In this work, 52 diphenyl-4,5-dihydroisoxazoles and -3-hydroxy ketones were prepared and their estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) activities were explored in order to systematize and maximize their biological activity. The biological activity was firstly screened by using ERE reporter assay to find out how aromatic hydroxylation and methylation of the chiral centers of the compounds affect the ability of ER to mediate biological responses. For selected 19 compounds, the relative binding affinities (RBA, relative to 3,17 beta-estradiol) and ability to induce transcription of primary E2 target gene pS2 in human MCF-7 breast cancer cells were determined. In the reporter assay, many compounds showed even stronger activity than E2 and some of them showed RBA larger than 1%. The highest RBAs were determined for the enantiomers of 1-hydroxy-6-(4-hydroxy-phenyl)-1-phenyl-hexan-3-one (50a and 50b). Isomer 50a showed high binding affinity both to ER alpha (with RBA similar to 200%) and ERb (with RBA similar to 60%), while the RBAs of 50b were ca. 40% of those. Some of the other compounds (with RBA similar to 1-16%) showed also notable ERa binding selectivity. When four most promising ligands (50a, 50b, 45a, and 45b) were studied with respect to their ability to induce the transcription of primary E2 target gene pS2, the compounds acted as agonists or partial agonists. Computer modeling was used to predict receptor binding conformations and to rationalize the RBA differences of the compounds. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.007

文献信息

• NOVEL BETA-HYDROXYKETONES AND BETA-ALKOXYKETONES WITH ESTROGENIC ACTIVITY
  申请人：Pulkkinen, Juha

  公开号：EP2227449A1

  公开（公告）日：2010-09-15
• [EN] NOVEL BETA-HYDROXYKETONES AND BETA-ALKOXYKETONES WITH ESTROGENIC ACTIVITY<br/>[FR] NOUVELLES BÊTA-HYDROXYCÉTONES ET BÊTA-ALCOXYCÉTONES PRÉSENTANT UNE ACTIVITÉ OESTROGÉNIQUE
  申请人：PULKKINEN JUHA

  公开号：WO2009066008A1

  公开（公告）日：2009-05-28

  This invention relates to β-hydroxyketones and β-alkoxyketones of formula (I), to their use as estrogen receptor modulators, and to methods for their preparation.
• Synthesis and biological evaluation of phenolic 4,5-dihydroisoxazoles and 3-hydroxy ketones as estrogen receptor α and β agonists
  作者：Pekka K. Poutiainen、Tuomas A. Venäläinen、Mikael Peräkylä、Juha M. Matilainen、Sami Väisänen、Paavo Honkakoski、Reino Laatikainen、Juha T. Pulkkinen

  DOI：10.1016/j.bmc.2010.04.007

  日期：2010.5

  In this work, 52 diphenyl-4,5-dihydroisoxazoles and -3-hydroxy ketones were prepared and their estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) activities were explored in order to systematize and maximize their biological activity. The biological activity was firstly screened by using ERE reporter assay to find out how aromatic hydroxylation and methylation of the chiral centers of the compounds affect the ability of ER to mediate biological responses. For selected 19 compounds, the relative binding affinities (RBA, relative to 3,17 beta-estradiol) and ability to induce transcription of primary E2 target gene pS2 in human MCF-7 breast cancer cells were determined. In the reporter assay, many compounds showed even stronger activity than E2 and some of them showed RBA larger than 1%. The highest RBAs were determined for the enantiomers of 1-hydroxy-6-(4-hydroxy-phenyl)-1-phenyl-hexan-3-one (50a and 50b). Isomer 50a showed high binding affinity both to ER alpha (with RBA similar to 200%) and ERb (with RBA similar to 60%), while the RBAs of 50b were ca. 40% of those. Some of the other compounds (with RBA similar to 1-16%) showed also notable ERa binding selectivity. When four most promising ligands (50a, 50b, 45a, and 45b) were studied with respect to their ability to induce the transcription of primary E2 target gene pS2, the compounds acted as agonists or partial agonists. Computer modeling was used to predict receptor binding conformations and to rationalize the RBA differences of the compounds. (C) 2010 Elsevier Ltd. All rights reserved.