Methyl 2-[4-[9-bicyclo[3.3.1]nonanylidene-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]phenoxy]acetate | 1220520-23-9

• 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: Methyl 2-[4-[9-bicyclo[3.3.1]nonanylidene-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]phenoxy]acetate
• CAS: 1220520-23-9
• 化学式: C₃₁H₄₂O₄Si
• 分子量: 506.758
• InChiKey: ULQWTUMLWOTSPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.02
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 2-[4-[9-bicyclo[3.3.1]nonanylidene-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]phenoxy]acetate 在 potassium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以93%的产率得到2-[4-[9-Bicyclo[3.3.1]nonanylidene-(4-hydroxyphenyl)methyl]phenoxy]acetic acid
  参考文献：
  名称：

  Characterization of the Pharmacophore Properties of Novel Selective Estrogen Receptor Downregulators (SERDs)

  摘要：

  Selective estrogen receptor (ER) down-regulators (SERDs) reduce ER alpha protein levels as well as block ER activity and therefore are promising therapeutic agents for the treatment of hormone refractory breast cancer. Starting with the triarylethylene acrylic acid SERD 4, we have investigated how alterations in both the ligand core structure and the appended acrylic acid substituent affect SERD activity. The new ligands were based on high affinity, symmetrical cyclofenil or bicyclo[3.3.1]nonane core systems, and in these, the position of the carboxyl group was extended from the ligand core, either retaining the vinylic linkage of the substituent or replacing it with an ether linkage. Although most structural variants showed binding affinities for ER alpha and ER beta higher than that of 4, only the compounds preserving the acrylic acid side chain retained SERD activity, although they could possess varying core structures. Hence, the acrylic acid moiety of the ligand is crucial for SERD-like blockade of ER activities.

  DOI：

  10.1021/jm100047k
• 作为产物：
  描述：

  9-[(4-(tert-butyldimethylsilyloxy)phenyl)(4-hydroxyphenyl)methylene]bicyclo[3.3.1]nonane 、 溴乙酸甲酯 在 caesium carbonate 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 反应 24.0h， 以82%的产率得到Methyl 2-[4-[9-bicyclo[3.3.1]nonanylidene-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]phenoxy]acetate
  参考文献：
  名称：

  Characterization of the Pharmacophore Properties of Novel Selective Estrogen Receptor Downregulators (SERDs)

  摘要：

  Selective estrogen receptor (ER) down-regulators (SERDs) reduce ER alpha protein levels as well as block ER activity and therefore are promising therapeutic agents for the treatment of hormone refractory breast cancer. Starting with the triarylethylene acrylic acid SERD 4, we have investigated how alterations in both the ligand core structure and the appended acrylic acid substituent affect SERD activity. The new ligands were based on high affinity, symmetrical cyclofenil or bicyclo[3.3.1]nonane core systems, and in these, the position of the carboxyl group was extended from the ligand core, either retaining the vinylic linkage of the substituent or replacing it with an ether linkage. Although most structural variants showed binding affinities for ER alpha and ER beta higher than that of 4, only the compounds preserving the acrylic acid side chain retained SERD activity, although they could possess varying core structures. Hence, the acrylic acid moiety of the ligand is crucial for SERD-like blockade of ER activities.

  DOI：

  10.1021/jm100047k