2-(3-fluoro-4-iodophenyl)propanoic acid | 749917-25-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(3-fluoro-4-iodophenyl)propanoic acid
• 英文别名: 2-(3-fluoro-4-iodophenyl)propionic acid
• CAS: 749917-25-7
• 化学式: C₉H₈FIO₂
• 分子量: 294.064
• InChiKey: LWVDGOUORVCLSO-UHFFFAOYSA-N

物化性质

• 沸点：
  330.4±32.0 °C(Predicted)
• 密度：
  1.833±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-fluoro-4-iodophenyl)propanoic acid 在 吡啶 、 四(三苯基膦)钯 、 草酰氯 、 氨 、 sodium carbonate 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 2-(2-fluoro-4'-trifluoromethylbiphenyl-4-yl)propionitrile
  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：

  2-[(3-氟-4-硝基苯基)甲基]丙二酸二乙基酯 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 100.0 ℃ 、300.01 kPa 条件下， 反应 21.5h， 生成 2-(3-fluoro-4-iodophenyl)propanoic acid
  参考文献：
  名称：

  Development of Biaryl-Containing Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors for Reversing AKR1C3-Mediated Drug Resistance in Cancer Treatment

  摘要：

  DOI：

  10.1021/acs.jmedchem.3c00213

文献信息

• Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies
  作者：Marco Migliore、Damien Habrant、Oscar Sasso、Clara Albani、Sine Mandrup Bertozzi、Andrea Armirotti、Daniele Piomelli、Rita Scarpelli

  DOI：10.1016/j.ejmech.2015.12.036

  日期：2016.2

  Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.
• [EN] 1-PHENYL-2- MONOALKYL CARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] DERIVES D'ACIDE 1-PHENYL-2-MONOALKYL-CARBOXYLIQUE POUR LE TRAITEMENT DE MALADIES NEURODEGENERATIVES
  申请人：CHIESI FARMA SPA

  公开号：WO2004073705A1

  公开（公告）日：2004-09-02

  Novel 1-phenyl-2-monoalkylcarboxylic derivatives, the process for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer’s disease.