4’-甲氧基氟比洛芬 | 41635-83-0

• 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: 4’-甲氧基氟比洛芬
• 中文别名: 4'-甲氧基氟比洛芬
• 英文名称: 2-(2-fluoro-4'-methoxy-4-biphenylyl)propionic acid
• 英文别名: 2-[3-fluoro-4-(4-methoxyphenyl)phenyl]propanoic Acid
• CAS: 41635-83-0
• 化学式: C₁₆H₁₅FO₃
• 分子量: 274.292
• InChiKey: ADNQRQZIGOHTSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4’-甲氧基氟比洛芬 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 生成 4'-羟基氟比洛芬
  参考文献：
  名称：

  DE2329125

  摘要：

  公开号：
• 作为产物：
  描述：

  2-[(3-氟-4-硝基苯基)甲基]丙二酸二乙基酯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 四(三苯基膦)钯 、 氢气 、 sodium carbonate 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 12.0h， 生成 4’-甲氧基氟比洛芬
  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

文献信息

• Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C–Cl site
  作者：Zicong Chen、Changxue Gu、On Ying Yuen、Chau Ming So

  DOI：10.1039/d1sc06701j

  日期：——

  study described palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates in the Ar–Cl bond. The Pd/SelectPhos system showed excellent chemoselectivity toward the Ar–Cl bond in the presence of the Ar–OTf bond with a broad substrate scope and excellent product yields. The electronic and steric hindrance offered by the –PR2 group of the ligand with the C2-alkyl

  本研究描述了在 Ar-Cl 键中用三氟甲磺酸氯芳基酯对羰基化合物进行钯催化的化学选择性直接 α-芳基化。在 Ar-OTf 键存在的情况下，Pd/SelectPhos 系统对 Ar-Cl 键表现出优异的化学选择性，具有广泛的底物范围和优异的产物产率。发现由C2-烷基配体的-PR 2基团提供的电子和空间位阻是影响α-芳基化反应的反应性和化学选择性的关键因素。化学发散方法也成功地用于氟比洛芬及其衍生物（例如，-OMe 和-F）的合成。
• 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。
• Novel thiazole derivatives
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0511021A1

  公开（公告）日：1992-10-28

  A novel thiazole derivative of formula [1] or a pharmaceutically acceptable salt thereof: wherein A is a singe bond, straight-chained or branched-chained lower alkylene or straight-chained or branched lower alkenylene, B is a single bond or -CO-; R¹ is carboxy or -CON(R⁷)OR⁸ (R⁷ and R⁸ are the same or different and each is hydrogen or lower alkyl); R² is lower alkyl; R³ and R⁴ are the same or different and each is hydrogen, lower alkyl or lower alkoxycarbonyl; R⁵ is hydrogen or halogen; and R⁶ is hydrogen, halogen, lower alkyl, hydroxy, lower alkoxy, thiol, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, nitro, amino, substituted amino, cyano, carboxy or acyl. The compounds of the present invention are useful as therapeutic or preventive drugs for autoimmune diseases and inflammatory diseases.

  式[1]的新型噻唑衍生物或其药学上可接受的盐： 其中 A 为单键、直链或支链低级亚烷基或直链或支链低级烯基，B 为单键或-CO-；R¹ 为羧基或-CON(R⁷)OR⁸ (R⁷ 和 R⁸ 相同或不同，且各自为氢或低级烷基)；R² 为低级烷基；R³和R⁴相同或不同，且各自为氢、低级烷基或低级烷氧基羰基；R⁵为氢或卤素；以及R⁶为氢、卤素、低级烷基、羟基、低级烷氧基、硫醇、低级烷硫基、低级烷基亚磺酰基、低级烷基磺酰基、硝基、氨基、取代氨基、氰基、羧基或酰基。 本发明的化合物可作为治疗或预防自身免疫性疾病和炎症性疾病的药物。
• EP1603548A4
  申请人：——

  公开号：EP1603548A4

  公开（公告）日：2007-10-10
• METHOD AND COMPOSITION FOR TREATING NEURODEGENERATIVE DISORDERS
  申请人：MYRIAD GENETICS, INC.

  公开号：EP1603548A2

  公开（公告）日：2005-12-14