2-Ethyl-2-(2-fluoro-biphenyl-4-yl)-butyric acid | 866235-92-9

• 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: 2-Ethyl-2-(2-fluoro-biphenyl-4-yl)-butyric acid
• 英文别名: 2-ethyl-2-(3-fluoro-4-phenylphenyl)butanoic acid
• CAS: 866235-92-9
• 化学式: C₁₈H₁₉FO₂
• 分子量: 286.346
• InChiKey: AWNQOTCRVVFDHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 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 、 sodium hydroxide 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 11.0h， 生成 2-Ethyl-2-(2-fluoro-biphenyl-4-yl)-butyric 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

文献信息

• PHARMACEUTICAL COMPOSITION AND METHOD
  申请人：Slade Rachel M.

  公开号：US20090155903A1

  公开（公告）日：2009-06-18

  The invention provides compounds, pharmaceutical compositions and methods for the therapeutic treatment and prevention of neurodegenerative disorder and other Aβ 42 -related diseases and disorders.

  该发明提供了化合物、制药组合物和方法，用于治疗和预防神经退行性疾病和其他与Aβ42相关的疾病和障碍。
• [EN] COMPOUNDS FOR NEURODEGENERATIVE DISORDERS<br/>[FR] COMPOSES DESTINES AUX TROUBLES NEURODEGENERATIFS
  申请人：MYRIAD GENETICS INC

  公开号：WO2005092062A2

  公开（公告）日：2005-10-06

  The invention provides compounds, pharmaceutical compositions and methods for the therapeutic treatment and prevention of neurodegenerative disorders and other Aβ42-related diseases and disorders.
• 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.