(±)-methyl 2-[4-nitro-3-(trifluoromethyl)phenyl]propanoate | 93742-93-9

• 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: (±)-methyl 2-[4-nitro-3-(trifluoromethyl)phenyl]propanoate
• 英文别名: methyl 2-(4-nitro-3-trifluoromethylbenzene)propionate；Methyl 2-[4-nitro-3-(trifluoromethyl)phenyl]propanoate
• CAS: 93742-93-9
• 化学式: C₁₁H₁₀F₃NO₄
• 分子量: 277.2
• InChiKey: OPNLBVIKDXAQMT-UHFFFAOYSA-N

物化性质

• 沸点：
  303.1±42.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (±)-methyl 2-[4-nitro-3-(trifluoromethyl)phenyl]propanoate 在 盐酸 、 palladium 10% on activated carbon 、 甲酸铵 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 4.5h， 生成 (±)-methyl 2-[4-iodo-3-(trifluoromethyl)phenyl]propanoate
  参考文献：
  名称：

  Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.12.036
• 作为产物：
  描述：

  2-硝基-Alpha,Alpha,Alpha-三氟甲苯 在 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 (±)-methyl 2-[4-nitro-3-(trifluoromethyl)phenyl]propanoate
  参考文献：
  名称：

  Nucleophilic substitution process

  摘要：

  硝基芳基乙酸酯是通过在惰性溶剂中，在碱的存在下，将带有硝基的芳环上没有卤素的硝基芳香化合物与α，α-二取代的乙酸酯反应，使酯在硝基芳香化合物的未取代环碳上发生亲核取代反应，期间α-取代基作为离去基团。硝基苯乙酸及其酯是合成药物的有用中间体。

  公开号：

  US04476315A1

文献信息

• US4476315A
  申请人：——

  公开号：US4476315A

  公开（公告）日：1984-10-09
• 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.
• Nucleophilic substitution process
  申请人：Ethyl Corporation

  公开号：US04476315A1

  公开（公告）日：1984-10-09

  Nitroarylacetic acid esters are prepared by reacting a nitroaromatic compound which is devoid of halogen on the aromatic ring carrying a nitro group with an alpha,alpha-disubstituted acetic acid ester in an inert solvent and in the presence of a base so that the ester undergoes a nucleophilic substitution on an unsubstituted ring carbon of the nitroaromatic compound during which an alpha-substituent functions as a leaving group. Nitrobenzene acetic acids and their esters are useful intermediates for the synthesis of pharmaceuticals.

  硝基芳基乙酸酯是通过在惰性溶剂中，在碱的存在下，将带有硝基的芳环上没有卤素的硝基芳香化合物与α，α-二取代的乙酸酯反应，使酯在硝基芳香化合物的未取代环碳上发生亲核取代反应，期间α-取代基作为离去基团。硝基苯乙酸及其酯是合成药物的有用中间体。