1-(2-fluoro-4'-hydroxybiphenyl-4-yl)cyclopropanecarboxylic acid | 749269-80-5

• 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: 1-(2-fluoro-4'-hydroxybiphenyl-4-yl)cyclopropanecarboxylic acid
• 英文别名: CHF 5070；1-(2-fluoro-4'-hydroxybiphenyl-4-yl)-cyclopropanecarboxylic acid；1-(2-Fluoro-4'-hydroxy-biphenyl-4-yl)-cyclopropanecarboxylic acid；1-[3-fluoro-4-(4-hydroxyphenyl)phenyl]cyclopropane-1-carboxylic acid
• CAS: 749269-80-5
• 化学式: C₁₆H₁₃FO₃
• 分子量: 272.276
• InChiKey: BHYFPOMNUGVUDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-fluoro-4'-hydroxybiphenyl-4-yl)cyclopropanecarboxylic acid 在 硫酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid_1-42 Secretion

  摘要：

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

  DOI：

  10.1021/jm0502541
• 作为产物：
  描述：

  potassium carbonate 、 1-(4-溴-3-氟苯基)环丙烷-1-羧酸 、 Hydroperoxy(phenyl)borinic acid 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 氮气 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 1-(2-fluoro-4'-hydroxybiphenyl-4-yl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  Derivatives of 1-phenylalkanecarboxylic acids for the treatment of neurodegenerative diseases

  摘要：

  本发明涉及1-苯基脂肪酸衍生物、其制药组合物、其制备方法以及它们用于治疗和/或预防神经退行性疾病如阿尔茨海默病的用途。

  公开号：

  US07531692B2

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。
• Derivatives of 1-Phenylalkanecarboxylic Acids for the Treatment of Neurodegenerative Diseases
  申请人：Raveglia Luca

  公开号：US20080096968A1

  公开（公告）日：2008-04-24

  The present invention concerns novel derivatives of 1-phenylalkanecarboxylic acids, pharmaceutical compositions thereof, a process for their preparation and their use for the treatment and/or prevention of neurodegenerative diseases such as Alzheimer' s disease.

  本发明涉及1-苯基脂肪酸衍生物的新颖衍生物，其制药组合物，其制备方法以及其用于治疗和/或预防神经退行性疾病，如阿尔茨海默病的用途。
• 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。