bis(3-methyl-4-(3,3-dimethyl-2-oxobutoxy)phenyl)diethylsilane | 1174552-98-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: bis(3-methyl-4-(3,3-dimethyl-2-oxobutoxy)phenyl)diethylsilane
• 英文别名: 1-[4-[[4-(3,3-Dimethyl-2-oxobutoxy)-3-methylphenyl]-diethylsilyl]-2-methylphenoxy]-3,3-dimethylbutan-2-one
• CAS: 1174552-98-7
• 化学式: C₃₀H₄₄O₄Si
• 分子量: 496.762
• InChiKey: WEUQGGPXEFMBPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.89
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-2-甲基苯酚 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.0h， 生成 bis(3-methyl-4-(3,3-dimethyl-2-oxobutoxy)phenyl)diethylsilane
  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

• Discovery of diphenylmethane analogs as anti-bovine diarrhea viral agents
  作者：Shinnosuke Hosoda、Hiroshi Aoyama、Yukinori Goto、Mohammed T.A. Salim、Mika Okamoto、Mariko Hashimoto、Masanori Baba、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2009.04.137

  日期：2009.6

  Based on antiviral screening of our diphenylmethane derivatives prepared as steroid substitutes, we identified a 1,1-diphenylcyclobutane analog (9) and two diethyldiphenylsilane analogs (12 and 13) as superior lead compounds with potent anti-bovine viral diarrhea virus (BVDV) activity, having 50% effective concentration (EC50: based on reduction of BVDV replication-induced cell destruction) and 50% cytotoxic concentration (CC50: based on reduction of viable cell number) values of 6.2-8.4 mu M and >100 mu M, respectively, in Madin-Darby bovine kidney (MDBK) cells infected with BVDV. (C) 2009 Elsevier Ltd. All rights reserved.
• 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.