1-[4-[[4-[(2S)-2,3-dihydroxypropoxy]-3-methylphenyl]-diethylsilyl]-2-methylphenoxy]-3,3-dimethylbutan-2-one | 1427540-79-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[4-[[4-[(2S)-2,3-dihydroxypropoxy]-3-methylphenyl]-diethylsilyl]-2-methylphenoxy]-3,3-dimethylbutan-2-one
• CAS: 1427540-79-1
• 化学式: C₂₇H₄₀O₅Si
• 分子量: 472.697
• InChiKey: XRFCYQRGFVMHRQ-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[4-[[4-[(2S)-2,3-dihydroxypropoxy]-3-methylphenyl]-diethylsilyl]-2-methylphenoxy]-3,3-dimethylbutan-2-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以84.1%的产率得到(2S)-3-(4-(diethyl(4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl)silyl)-2-methylphenoxy)propane-1,2-diol
  参考文献：
  名称：

  Development of silicon-containing bis-phenol derivatives as androgen receptor antagonists: Selectivity switching by C/Si exchange

  摘要：

  We previously reported that bis-phenol derivatives, including LG190178 (3a), possess not only vitamin D receptor (VDR) agonistic activity, but also androgen receptor (AR) antagonistic activity. Here, we describe the design, synthesis and evaluation of silicon-containing bis-phenol derivatives, with the objective of obtaining increased selectivity toward VDR or AR. We found that replacement of the quaternary carbon in the his-phenol skeleton with silicon increased AR-antagonistic activity and reduced VDR-agonistic activity, that is, the AR selectivity of the silicon-containing compounds was higher than that of corresponding carbon compounds. To our knowledge, this is the first report of nuclear receptor (NR) selectivity switching by sila-substitution (C/Si exchange). Among the compounds synthesized, AR-selective ligand (S,R)-3b exhibited more potent anti-androgenic activity (IC50 = 0.072 mu M) than hydroxyflutamide, a well-known androgen antagonist (IC50 = 1.4 mu M), in SC-3 cell proliferation assay. These results suggest that sila-substitution is a useful approach for structural development of selective AR ligands. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.060
• 作为产物：
  描述：

  1-(4-(diethyl(4-hydroxy-3-methylphenyl)silyl)-2-methylphenoxy)-3,3-dimethylbutan-2-one 、 (S)-缩水甘油 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.5h， 以46.2%的产率得到1-[4-[[4-[(2S)-2,3-dihydroxypropoxy]-3-methylphenyl]-diethylsilyl]-2-methylphenoxy]-3,3-dimethylbutan-2-one
  参考文献：
  名称：

  Development of silicon-containing bis-phenol derivatives as androgen receptor antagonists: Selectivity switching by C/Si exchange

  摘要：

  We previously reported that bis-phenol derivatives, including LG190178 (3a), possess not only vitamin D receptor (VDR) agonistic activity, but also androgen receptor (AR) antagonistic activity. Here, we describe the design, synthesis and evaluation of silicon-containing bis-phenol derivatives, with the objective of obtaining increased selectivity toward VDR or AR. We found that replacement of the quaternary carbon in the his-phenol skeleton with silicon increased AR-antagonistic activity and reduced VDR-agonistic activity, that is, the AR selectivity of the silicon-containing compounds was higher than that of corresponding carbon compounds. To our knowledge, this is the first report of nuclear receptor (NR) selectivity switching by sila-substitution (C/Si exchange). Among the compounds synthesized, AR-selective ligand (S,R)-3b exhibited more potent anti-androgenic activity (IC50 = 0.072 mu M) than hydroxyflutamide, a well-known androgen antagonist (IC50 = 1.4 mu M), in SC-3 cell proliferation assay. These results suggest that sila-substitution is a useful approach for structural development of selective AR ligands. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.060

文献信息

• Development of silicon-containing bis-phenol derivatives as androgen receptor antagonists: Selectivity switching by C/Si exchange
  作者：Masaharu Nakamura、Makoto Makishima、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2013.01.060

  日期：2013.4

  We previously reported that bis-phenol derivatives, including LG190178 (3a), possess not only vitamin D receptor (VDR) agonistic activity, but also androgen receptor (AR) antagonistic activity. Here, we describe the design, synthesis and evaluation of silicon-containing bis-phenol derivatives, with the objective of obtaining increased selectivity toward VDR or AR. We found that replacement of the quaternary carbon in the his-phenol skeleton with silicon increased AR-antagonistic activity and reduced VDR-agonistic activity, that is, the AR selectivity of the silicon-containing compounds was higher than that of corresponding carbon compounds. To our knowledge, this is the first report of nuclear receptor (NR) selectivity switching by sila-substitution (C/Si exchange). Among the compounds synthesized, AR-selective ligand (S,R)-3b exhibited more potent anti-androgenic activity (IC50 = 0.072 mu M) than hydroxyflutamide, a well-known androgen antagonist (IC50 = 1.4 mu M), in SC-3 cell proliferation assay. These results suggest that sila-substitution is a useful approach for structural development of selective AR ligands. (C) 2013 Elsevier Ltd. All rights reserved.