5-methyl-3-phenethyl-5-phenyl-4,5-dihydroisoxazole | 1158557-96-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-methyl-3-phenethyl-5-phenyl-4,5-dihydroisoxazole
• 英文别名: 5-Methyl-3-phenethyl-5-phenyl-4,5-dihydroisoxazole (enantiomeric mix)；5-methyl-5-phenyl-3-(2-phenylethyl)-4H-1,2-oxazole
• CAS: 1158557-96-0
• 化学式: C₁₈H₁₉NO
• 分子量: 265.355
• InChiKey: VNXPGUGQXFYHAW-UHFFFAOYSA-N

物化性质

• 沸点：
  394.7±52.0 °C(predicted)
• 密度：
  1.05±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-3-phenethyl-5-phenyl-4,5-dihydroisoxazole 在 水 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以73%的产率得到5-hydroxy-1,5-diphenyl-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
• 作为产物：
  描述：

  (NE)-N-(3-苯基亚丙基)羟胺 、 2-苯基-1-丙烯 在 吡啶 、 sodium hypochlorite 作用下， 以 二氯甲烷 为溶剂， 以18%的产率得到5-methyl-3-phenethyl-5-phenyl-4,5-dihydroisoxazole
  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

• [EN] NOVEL 4,5-DIHYDROISOXAZOLES WITH ESTROGENIC ACTIVITY<br/>[FR] NOUVEAUX 4,5-DIHYDROISOXAZOLES AVEC UNE ACTIVITÉ OETROGÉNIQUE
  申请人：PULKKINEN JUHA

  公开号：WO2009066009A1

  公开（公告）日：2009-05-28

  This invention relates to novel 4,5-dihydroisoxazoles of formula (I), to their use as estrogen receptor modulators, and to methods of their preparation.

  该发明涉及新型的4,5-二氢异噁唑（I）的公式，以及它们作为雌激素受体调节剂的用途，以及它们的制备方法。
• [EN] NOVEL NON-STEROIDAL COMPOUNDS AS ANDROGEN RECEPTOR MODULATORS<br/>[FR] NOUVEAUX COMPOSÉS NON STÉROÏDES EN TANT QUE MODULATEURS D'UN RÉCEPTEUR DES ANDROGÈNES
  申请人：PULKKINEN JUHA

  公开号：WO2013057372A1

  公开（公告）日：2013-04-25

  This invention relates to novel 4,5-dihydroisoxazoles and 4,5-dihydro[1,2,4]-oxadiazoles of formula (I), to their use as androgenic or antiandrogenic agents or androgen receptor modulators, and to methods of their preparation.

  本发明涉及一种新型的4,5-二氢异噁唑和4,5-二氢[1,2,4]-噁二唑化合物，其化学式为(I)，以及它们作为雄激素或抗雄激素剂或雄激素受体调节剂的用途和它们的制备方法。
• NOVEL 4,5-DIHYDROISOXAZOLES WITH ESTROGENIC ACTIVITY
  申请人：Pulkkinen, Juha

  公开号：EP2222653A1

  公开（公告）日：2010-09-01
• US20140275186A1
  申请人：——

  公开号：US20140275186A1

  公开（公告）日：2014-09-18
• US9278942B2
  申请人：——

  公开号：US9278942B2

  公开（公告）日：2016-03-08