Tert-butyl-[1-[tert-butyl(dimethyl)silyl]oxy-2-(3-fluoro-4-phenylphenyl)ethenoxy]-dimethylsilane | 1279100-90-1

• 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: Tert-butyl-[1-[tert-butyl(dimethyl)silyl]oxy-2-(3-fluoro-4-phenylphenyl)ethenoxy]-dimethylsilane
• CAS: 1279100-90-1
• 化学式: C₂₆H₃₉FO₂Si₂
• 分子量: 458.764
• InChiKey: XMPXPYDFTSGWNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.83
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl-[1-[tert-butyl(dimethyl)silyl]oxy-2-(3-fluoro-4-phenylphenyl)ethenoxy]-dimethylsilane 在 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium tetrafluoroborate 作用下， 以 乙腈 为溶剂， 以38.2%的产率得到2-fluoro-2-(2-fluorobiphenyl-4-yl)acetic acid
  参考文献：
  名称：

  Inhibition of Amyloidogenesis by Nonsteroidal Anti-inflammatory Drugs and Their Hybrid Nitrates

  摘要：

  Poor blood-brain barrier penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer's disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogues were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (I) analogues were obtained with enhanced anti-inflammatory and antiamyloidogenic properties compared to I, however, esterification led to elevated A beta(1-42) levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate CHF5074. Although hybrid nitrates elevated A beta(1-42) at higher concentration, SALA activity was observed at low concentrations (<= 1 mu M): both A beta(1-42) and the ratio of A beta(1-42)/A beta(1-40) were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds, the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach toward a clinically useful SALA.

  DOI：

  10.1021/jm101450p
• 作为产物：
  描述：

  4-溴-3-氟甲苯 在 N-溴代丁二酰亚胺(NBS) 、 四丁基溴化铵 、 双氧水 、 palladium diacetate 、 sodium carbonate 、 potassium carbonate 、 lithium hexamethyldisilazane 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 3.0h， 生成 Tert-butyl-[1-[tert-butyl(dimethyl)silyl]oxy-2-(3-fluoro-4-phenylphenyl)ethenoxy]-dimethylsilane
  参考文献：
  名称：

  Inhibition of Amyloidogenesis by Nonsteroidal Anti-inflammatory Drugs and Their Hybrid Nitrates

  摘要：

  Poor blood-brain barrier penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer's disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogues were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (I) analogues were obtained with enhanced anti-inflammatory and antiamyloidogenic properties compared to I, however, esterification led to elevated A beta(1-42) levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate CHF5074. Although hybrid nitrates elevated A beta(1-42) at higher concentration, SALA activity was observed at low concentrations (<= 1 mu M): both A beta(1-42) and the ratio of A beta(1-42)/A beta(1-40) were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds, the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach toward a clinically useful SALA.

  DOI：

  10.1021/jm101450p

文献信息

• Inhibition of Amyloidogenesis by Nonsteroidal Anti-inflammatory Drugs and Their Hybrid Nitrates
  作者：Isaac T. Schiefer、Samer Abdul-Hay、Huali Wang、Michael Vanni、Zhihui Qin、Gregory R. J. Thatcher

  DOI：10.1021/jm101450p

  日期：2011.4.14

  Poor blood-brain barrier penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer's disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogues were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (I) analogues were obtained with enhanced anti-inflammatory and antiamyloidogenic properties compared to I, however, esterification led to elevated A beta(1-42) levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate CHF5074. Although hybrid nitrates elevated A beta(1-42) at higher concentration, SALA activity was observed at low concentrations (<= 1 mu M): both A beta(1-42) and the ratio of A beta(1-42)/A beta(1-40) were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds, the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach toward a clinically useful SALA.