3-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-[[tert-butyl(dimethyl)silyl]oxy]-3-fluorophenyl)-1-naphthonitrile | 858946-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-[[tert-butyl(dimethyl)silyl]oxy]-3-fluorophenyl)-1-naphthonitrile
• 英文别名: 3-[Tert-butyl(dimethyl)silyl]oxy-7-[4-[tert-butyl(dimethyl)silyl]oxy-3-fluorophenyl]naphthalene-1-carbonitrile
• CAS: 858946-78-8
• 化学式: C₂₉H₃₈FNO₂Si₂
• 分子量: 507.796
• InChiKey: FZDIMXQKRDAOGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.29
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-[[tert-butyl(dimethyl)silyl]oxy]-3-fluorophenyl)-1-naphthonitrile 在 正丁基锂 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.92h， 生成 6-(3-Fluoro-4-hydroxy-phenyl)-4-vinyl-naphthalen-2-ol
  参考文献：
  名称：

  ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity

  摘要：

  The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.

  DOI：

  10.1021/jm058173s
• 作为产物：
  描述：

  7-羟基-1-萘甲腈 在 吡啶 、 咪唑 、 四(三苯基膦)钯 、 C₆H₅N*HCl 、 溴 、 sodium carbonate 、 溶剂黄146 、 copper(I) bromide 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 3-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-[[tert-butyl(dimethyl)silyl]oxy]-3-fluorophenyl)-1-naphthonitrile
  参考文献：
  名称：

  ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity

  摘要：

  The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.

  DOI：

  10.1021/jm058173s

文献信息

• ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity
  作者：Richard E. Mewshaw、Richard J. Edsall,、Cuijian Yang、Eric S. Manas、Zhang B. Xu、Ruth A. Henderson、James C. Keith,、Heather A. Harris

  DOI：10.1021/jm058173s

  日期：2005.6.1

  The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.