1-[3-氟-4-[4-(三氟甲基)苯基]苯基]环丙烷-1-羧酸 | 749269-77-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-[3-氟-4-[4-(三氟甲基)苯基]苯基]环丙烷-1-羧酸
• 英文名称: 1-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)cyclopropanecarboxylic acid
• 英文别名: Cyclopropanecarboxylic acid, 1-(2-fluoro-4'-(trifluoromethyl)(1,1'-biphenyl)-4-yl)-；1-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]cyclopropane-1-carboxylic acid
• CAS: 749269-77-0
• 化学式: C₁₇H₁₂F₄O₂
• 分子量: 324.275
• InChiKey: STSYUQWYKFKDNG-UHFFFAOYSA-N

物化性质

• 沸点：
  405.8±45.0 °C(Predicted)
• 密度：
  1.403±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[3-氟-4-[4-(三氟甲基)苯基]苯基]环丙烷-1-羧酸 在 草酰氯 、 silver nitrate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.0h， 生成 2-(nitrooxy)ethyl 1-(2-fluoro-4'-(trifluoromethyl)biphenyl-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：

  4-溴-3-氟甲苯 在 N-溴代丁二酰亚胺(NBS) 、 四丁基溴化铵 、 palladium diacetate 、 sodium carbonate 、 sodium hydroxide 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 水 、 甲苯 为溶剂， 反应 15.0h， 生成 1-[3-氟-4-[4-(三氟甲基)苯基]苯基]环丙烷-1-羧酸
  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

• [EN] 1-PHENYLALKANECARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] DERIVES D'ACIDE 1-PHENYLALCANE-CARBOXYLIQUE POUR LE TRAITEMENT DE MALADIES NEURODEGENERATIVES
  申请人：CHIESI FARMA SPA

  公开号：WO2004074232A1

  公开（公告）日：2004-09-02

  1-Phenylalkanecarboxylic acid derivatives, the processes for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer's disease.

  1-苯基烷基羧酸衍生物，其制备方法以及用于治疗和/或预防如阿尔茨海默病等神经退行性疾病的使用方法。
• Method and composition for treating neurodegenerative disorders
  申请人：Hobden Adrian

  公开号：US20050288375A1

  公开（公告）日：2005-12-29

  The invention provides compositions and methods for treating neurodegenerative disorders. A method of the invention involves administering to an individual in need of treatment a composition having an R-NSAID and an NMDA antagonist. Another method of the invention involves administering to an individual in need of treatment a composition having at least two compounds that are capable of interacting with CYP2C9, wherein at least one of said compounds is an Aβ 42 lowering agent. The methods and compositions of the invention are useful for treating and preventing neurodegenerative disorders like Alzheimer's disease, dementia, mild cognitive impairment.

  本发明提供了用于治疗神经退行性疾病的组合物和方法。该发明的一种方法涉及向需要治疗的个体施用具有R-NSAID和NMDA拮抗剂的组合物。该发明的另一种方法涉及向需要治疗的个体施用至少两种能够与CYP2C9相互作用的化合物的组合物，其中至少一种化合物是Aβ42降低剂。该发明的方法和组合物对于治疗和预防像阿尔茨海默病、痴呆症、轻度认知障碍等神经退行性疾病非常有用。
• Pharmaceutical Composition And Method For Treating Neurodegenerative Disorders
  申请人：Hobden Adrian

  公开号：US20070232656A1

  公开（公告）日：2007-10-04

  The invention provides compositions and methods for treating neurodegenerative disorders. The method of the invention involves administering to an individual in need of treatment a composition having an acetylcholine esterase inhibitor and another therapeutic agent. The methods and compositions of the invention are useful for treating and preventing neurodegenerative disorders like Alzheimer's disease, dementia, and mild cognitive impairment.

  本发明提供了治疗神经退行性疾病的组合物和方法。本发明的方法涉及向需要治疗的个体施用一种含有乙酰胆碱酯酶抑制剂和另一种治疗剂的组合物。本发明的方法和组合物对于治疗和预防阿尔茨海默病、痴呆和轻度认知障碍等神经退行性疾病是有用的。
• 1-Phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases
  申请人：Raveglia Luca

  公开号：US20070060752A1

  公开（公告）日：2007-03-15

  1-Phenylalkanecarboxylic acid derivatives, the processes for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer's disease.

  1-苯基烷基羧酸衍生物的制备方法、其在治疗和/或预防神经退行性疾病如阿尔茨海默病中的应用。
• 1-PHENYLALKANECARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：RAVEGLIA Luca

  公开号：US20100099768A1

  公开（公告）日：2010-04-22

  1-Phenylalkanecarboxylic acid derivatives, the processes for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer's disease.

  1-苯基烷基羧酸衍生物，其制备方法以及在治疗和/或预防神经退行性疾病如阿尔茨海默病中的用途。