2-methyl-2-(3-phenoxyphenyl)propanoic acid | 222191-15-3

• 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-methyl-2-(3-phenoxyphenyl)propanoic acid
• 英文别名: 2-Methyl-2-(3-phenoxy-phenyl)-propionic acid
• CAS: 222191-15-3
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: ITWDGOLFVXYKNJ-UHFFFAOYSA-N

物化性质

• 沸点：
  389.9±25.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 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：
  3

反应信息

• 作为产物：
  描述：

  3-(4-苯氧基苯基)丙酸 在 N,N-二甲基丙烯基脲 、 硫酸 、 potassium trimethylsilonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 2-methyl-2-(3-phenoxyphenyl)propanoic acid
  参考文献：
  名称：

  The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer’s disease modifying agent

  摘要：

  The subtle modification of a selection of A beta(42) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining A beta(42) inhibition. Methylflurbiprofen 6 exhibited similar in vitro A beta(42) inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.033

文献信息

• Unexpected formation of 3,3a,4,7a-tetrahydrobenzofuran-2,5-diones as well as arene carboxylic acids upon formal double exo nucleophilic addition of R1R2C−COO− to anisolechromium tricarbonyl complexes
  作者：Moncef Bellassoued、Evelyne Chelain、Jérôme Collot、Henri Rudler、Jacqueline Vaissermann

  DOI：10.1039/a808072k

  日期：——

  Bis(trimethylsily)ketene acetals of the general structure 2 (R1 = H, Me, R2 = Me, Et, Pri, CMe=CH2) react at –78 °C in the presence of ButOK with a series of arenechromium tricarbonyl complexes 3 to give as expected, after oxidation with I2 followed by silica gel chromatography, arylcarboxylic acids 7. In the case of anisolechromium tricarbonyl 8, besides the m-methoxyarylcarboxylic acids, tetrahydrobenzofuran-2,5-diones 11, are formed as the result of a double nucleophilic addition.

  一般结构为 2（R1 = H、Me，R2 = Me、Et、Pri，CMe=CH2）的双（三甲基硅基）乙烯乙醛在â78 °C下，在 ButOK 的存在下与一系列异铬三羰基络合物 3 发生反应，在用 I2 氧化后，通过硅胶色谱法得到芳基羧酸 7。在异olechromium tricarbonyl 8 的情况下，除了间甲氧基芳基羧酸外，还形成了四氢苯并呋喃-2,5-二酮 11，这是双重亲核加成的结果。
• 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。
• Geminallyl di-substituted nsaid derivatives as abeta 42 lowering agents
  申请人：Munoz Benito

  公开号：US20060063937A1

  公开（公告）日：2006-03-23

  The present invention encompasses compounds of Formula I (I) or pharmaceutically acceptable salts thereof, wherein A is the base molecule of a propionic acid or acetic acid NSAID, or a derivative thereof, X is —CO 2 H, 1H-tetrazol-5-yl or 2H-tetrazol-5-yl and R 1 and R 2 are each independently selected from the group consisting of: C 1-6 alkyl and C 3-6 cycloalkyl, as well as pharmaceutical composition comprising said compounds and methods of using said compounds. The compounds of the present invention lower the level of Aβ 42 and are therefore useful for preventing, delaying or reversing the progression of Alzheimer s Disease.

  本发明涵盖公式I（I）的化合物或其药学上可接受的盐，其中A是丙酸或乙酸非甾体抗炎药的基本分子或其衍生物，X为-CO2H，1H-四唑-5-基或2H-四唑-5-基，R1和R2各自独立地选自以下组：C1-6烷基和C3-6环烷基，以及包括所述化合物的制药组合物和使用所述化合物的方法。本发明的化合物降低Aβ42的水平，因此有助于预防、延缓或逆转阿尔茨海默病的进展。
• 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。
• Geminally di-substituted NSAID derivatives as Aβ42 lowering agents
  申请人：Merck + Co., Inc.

  公开号：US07332516B2

  公开（公告）日：2008-02-19

  The present invention encompasses compounds of Formula I (I) or pharmaceutically acceptable salts thereof, wherein A is the base molecule of a propionic acid or acetic acid NSAID, or a derivative thereof, X is —CO2H, 1H-tetrazol-5-yl or 2H-tetrazol-5-yl and R1 and R2 are each independently selected from the group consisting of: C1-6alkyl and C3-6cycloalkyl, as well as pharmaceutical composition comprising said compounds and methods of using said compounds. The compounds of the present invention lower the level of Aβ42 and are therefore useful for preventing, delaying or reversing the progression of Alzheimer's Disease.

  本发明涵盖了式I（I）的化合物或其药学上可接受的盐，其中A是丙酸或乙酸NSAID的基本分子或其衍生物，X是-CO2H，1H-四唑-5-基或2H-四唑-5-基，R1和R2各自独立地选自以下群体：C1-6烷基和C3-6环烷基，以及包括所述化合物的制药组合物和使用所述化合物的方法。本发明的化合物降低Aβ42的水平，因此对于预防、延缓或逆转阿尔茨海默病的进展是有用的。