2-(2-fluoro-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)propionic acid | 749269-75-8

• 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-(2-fluoro-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)propionic acid
• 英文别名: 2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)-propionic acid；2-(2-Fluoro-4'-trifluoromethylbiphenyl-4-yl)propionic acid；2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]propanoic acid
• CAS: 749269-75-8
• 化学式: C₁₆H₁₂F₄O₂
• 分子量: 312.264
• InChiKey: PAQRNRXJRSCEOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  2-(2-fluoro-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)propionic acid 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]-N-methylsulfonylpropanamide
  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：

  在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以48%的产率得到2-(2-fluoro-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)propionic acid
  参考文献：
  名称：

  AKR1C3抑制剂或其可药用的盐、其制备方法 及用途

  摘要：

  本发明公开了AKR1C3抑制剂或其可药用的盐、其制备方法及用途，以非甾体抗炎药氟比洛芬作为先导化合物进行结构的优化，公开了如式(I)的联苯类AKR1C3抑制剂及其制备方法，靶标活性测试证明，本发明的化合物具有可明显抑制AKR1C3的活性，可作为进一步开发为通过抑制醛酮还原酶AKR1C3来治疗和/或预防疾病的药物，为肿瘤耐药相关机制学研究奠定分子基础。

  公开号：

  CN110590548B

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。
• 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。
• 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：US08314268B2

  公开（公告）日：2012-11-20

  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及其在治疗和/或预防神经退行性疾病如阿尔茨海默病中的应用。
• [EN] AKR1C3 INHIBITOR OR PHARMACEUTICALLY ACCEPTABLE SALT OF SAME, PREPARATION METHOD FOR SAME, AND USES THEREOF<br/>[FR] INHIBITEUR DE AKR1C3 OU UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, PROCÉDÉ DE PRÉPARATION CORRESPONDANT ET UTILISATIONS ASSOCIÉES<br/>[ZH] AKR1C3抑制剂或其可药用的盐、其制备方法及用途
  申请人：UNIV CHINA PHARMA

  公开号：WO2021042411A1

  公开（公告）日：2021-03-11

  本发明公开了AKR1C3抑制剂或其可药用的盐、其制备方法及用途，以非甾体抗炎药氟比洛芬作为先导化合物进行结构的优化，公开了如 (I) 的联苯类AKR1C3抑制剂及其制备方法，靶标活性测试证明，本发明的化合物具有可明显抑制AKR1C3的活性，可作为进一步开发为通过抑制醛酮还原酶AKR1C3来治疗和/或预防疾病的药物，为肿瘤耐药相关机制学研究奠定分子基础。