4'-(tert-butyldimethylsilyloxy)biphenyl-4-carbaldehyde | 716344-19-3

• 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: 4'-(tert-butyldimethylsilyloxy)biphenyl-4-carbaldehyde
• 英文别名: 4'-(tert-butyl-dimethyl-silanyloxy)-biphenyl-4-carbaldehyde；4'-{[tert-butyl(dimethyl)silyl]oxy}-1,1'-biphenyl-4-carbaldehyde；4-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]benzaldehyde
• CAS: 716344-19-3
• 化学式: C₁₉H₂₄O₂Si
• 分子量: 312.484
• InChiKey: XRRMSCXSQBWAFH-UHFFFAOYSA-N

物化性质

• 沸点：
  386.2±35.0 °C(Predicted)
• 密度：
  1.012±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.55
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4'-(tert-butyldimethylsilyloxy)biphenyl-4-carbaldehyde 在 potassium fluoride 、 氢溴酸 作用下， 以 DMF (N,N-dimethyl-formamide) 、 水 为溶剂， 反应 2.5h， 以100%的产率得到4’-羟基(1,1’-联苯)-4-甲醛
  参考文献：
  名称：

  [EN] HYDROXY-BIPHENYL-CARBALDEHYDE OXIME DERIVATIVES AND THEIR USE AS ESTROGENIC AGENTS
  [FR] DERIVES D'OXIME HYDROXY-BIPHENYL-CARBALDEHYDE ET LEUR UTILISATION COMME AGENTS OESTROGENES

  摘要：

  公开号：

  WO2004099122A3
• 作为产物：
  描述：

  (4-溴苯氧基)叔丁基二甲基硅烷 在 四(三苯基膦)钯 正丁基锂 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 水 为溶剂， 反应 4.67h， 生成 4'-(tert-butyldimethylsilyloxy)biphenyl-4-carbaldehyde
  参考文献：
  名称：

  ERβ Ligands. Part 2: Synthesis and structure–activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivatives

  摘要：

  A series of biphenyl carbaldehyde oximes (6) was prepared and shown to have significant selectivity for the estrogen receptor-beta (ERbeta). The exploitation of the oxime moiety as a hydrogen bond donating group, which mimicked the C-ring of genistein makes these compounds unique. Molecular modeling studies showed the oxime moiety hydrogen bonding to the histidine residue, which was supported by the structure-activity relationships. The most potent compounds in this study had IC50 values in a radio-liaand binding assay of between 8-35 nM. Among the most selective compounds were 6i and 6s (49- and 31-fold ERbeta selective, respectively). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.028

文献信息

• Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17α-hydroxylase-17,20-lyase (CYP17)—Part II: Core rigidification and influence of substituents at the methylene bridge
  作者：Qingzhong Hu、Matthias Negri、Kerstin Jahn-Hoffmann、Yan Zhuang、Sureyya Olgen、Marc Bartels、Ursula Müller-Vieira、Thomas Lauterbach、Rolf W. Hartmann

  DOI：10.1016/j.bmc.2008.07.011

  日期：2008.8

  Thirty-five novel substituted imidazolyl methylene biphenyls have been synthesized as CYP17 inhibitors for the potential treatment of prostate cancer. Their activities have been tested with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against CYP11B1, CYP11B2, and hepatic CYP enzymes 3A4, 1A2, 2B6 and 2D6. The core rigidified compounds (30-35)

  已合成了35种新型取代的咪唑基亚甲基联苯作为CYP17抑制剂，可用于治疗前列腺癌。已经用在大肠杆菌中表达的重组人CYP17测试了它们的活性。测试了有前途的化合物对CYP11B1，CYP11B2和肝CYP酶3A4、1A2、2B6和2D6的选择性。核心刚性化合物（30-35）是最活跃的化合物，比酮康唑更有效，并达到阿比特龙的活性。但是，它们不是非常有选择性。在大鼠中进一步检查了血浆中睾丸激素水平和药代动力学特性的另一种更有效且更具选择性的抑制剂（化合物23，IC（50）= 345 nM）。相较于参考文献Abiraterone，体内有23种活性更高，显示更长的血浆半衰期（10小时）和更高的生物利用度。使用我们的CYP17同源蛋白模型，与选定化合物进行对接研究，以研究抑制剂与活性位点氨基酸残基之间的可能相互作用。
• Novel CYP17 inhibitors: Synthesis, biological evaluation, structure–activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls
  作者：Ulrike E. Hille、Qingzhong Hu、Carsten Vock、Matthias Negri、Marc Bartels、Ursula Müller-Vieira、Thomas Lauterbach、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2009.01.002

  日期：2009.7

  therapies, for example with GnRH analogues. However, steroidal drugs are known for side effects which are due to affinities for steroid receptors. Therefore we decided to synthesize non-steroidal compounds mimicking the natural CYP17 substrates pregnenolone and progesterone. The synthesis and biological evaluation of a series of 15 novel and highly active non-steroidal CYP17 inhibitors are reported. The compounds

  最近，类固醇CYP17抑制剂阿比特龙进入治疗雄激素依赖性前列腺癌的II期临床试验。由于17α-羟化酶-17,20-裂合酶（CYP17）催化雄激素生物合成的最后一步，对该靶标的抑制不仅会影响睾丸，还会影响肾上腺雄激素的形成。因此，CYP17抑制剂应优于现有疗法，例如使用GnRH类似物。然而，由于类固醇受体的亲和力，类固醇药物的副作用是已知的。因此，我们决定合成模拟天然CYP17底物孕烯醇酮和孕酮的非甾体化合物。报道了一系列15种新型和高活性非甾体CYP17抑制剂的合成和生物学评估。这些化合物是通过Suzuki交叉偶联制备的，用在大肠杆菌中表达的重组人CYP17检测了格氏反应和与咪唑的CDI辅助的S N t反应及其抑制活性。进一步测试了有前途的化合物对肝酶CYP3A4和糖皮质激素形成酶CYP11B1的选择性。事实证明所有化合物均为有效的CYP17抑制剂。活性最高的化合物7和8比酮康唑具有更高的活性，其活性可与阿比特龙媲美（IC
• Hydroxy-biphenyl-carbaldehyde oxime derivatives and their use as estrogenic agents
  申请人：Mewshaw Eric Richard

  公开号：US20050020676A1

  公开（公告）日：2005-01-27

  This invention provides estrogen receptor modulators having the structure: wherein R 1 to R 6 and R 8 are as defined in the specification; or a pharmaceutically acceptable salt thereof.

  本发明提供了具有以下结构的雌激素受体调节剂：其中R1至R6和R8的定义如规范中所述；或其药学上可接受的盐。
• Hydroxy-Biphenyl-Carbaldehyde Oxime Derivatives and Their Use As Estrogenic Agents
  申请人：Mewshaw Eric Richard

  公开号：US20080033049A1

  公开（公告）日：2008-02-07

  This invention provides estrogen receptor modulators having the structure: wherein R 1 to R 6 and R 8 are as defined in the specification; or a pharmaceutically acceptable salt thereof.

  该发明提供了具有以下结构的雌激素受体调节剂：其中R1至R6和R8如规范中定义；或其药用盐。
• [EN] HYDROXY-BIPHENYL-CARBALDEHYDE OXIME DERIVATIVES AND THEIR USE AS ESTROGENIC AGENTS<br/>[FR] DERIVES D'OXIME HYDROXY-BIPHENYL-CARBALDEHYDE ET LEUR UTILISATION COMME AGENTS OESTROGENES
  申请人：WYETH CORP

  公开号：WO2004099122A3

  公开（公告）日：2005-02-17