2-bromoethyl 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylate | 1279100-97-8

• 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-bromoethyl 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylate
• 英文别名: 2-Bromoethyl 1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylate
• CAS: 1279100-97-8
• 化学式: C₁₈H₁₄BrCl₂FO₂
• 分子量: 432.116
• InChiKey: BCEIUTLCJLZQGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromoethyl 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylate 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以73%的产率得到2-(nitrooxy)ethyl 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylate
  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：

  1-(4-溴-3-氟苯基)环丙烷-1-羧酸 在 草酰氯 、 四丁基溴化铵 、 palladium diacetate 、 sodium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 2-bromoethyl 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylate
  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