(±)-methyl 2-(4-acetamidophenyl)propanoate | 71589-45-2

• 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-acetamidophenyl)propanoate
• 英文别名: methyl 2-(4-acetamidophenyl)propanoate；(+/-)-2-(4-acetylamino-phenyl)-propionic acid methyl ester；(+/-)-2-(4-Acetylamino-phenyl)-propionsaeure-methylester
• CAS: 71589-45-2
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: NIRSEKGTZNUZSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (±)-methyl 2-(4-acetamidophenyl)propanoate 在 盐酸 、 硫酸 、 硝酸 、 乙酸酐 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (±)-methyl 2-(4-iodo-3-nitrophenyl)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-(4-硝基苯基)丙酸甲酯 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 反应 1.0h， 生成 (±)-methyl 2-(4-acetamidophenyl)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

文献信息

• Site-Selective Catalytic Carboxylation of Unsaturated Hydrocarbons with CO₂ and Water
  作者：Morgane Gaydou、Toni Moragas、Francisco Juliá-Hernández、Ruben Martin

  DOI：10.1021/jacs.7b07637

  日期：2017.9.6

  A catalytic protocol that reliably predicts and controls the site-selective incorporation of CO2 to a wide range of unsaturated hydrocarbons utilizing water as formal hydride source is described. This platform unlocks an opportunity to catalytically repurpose three abundant, orthogonal feedstocks under mild conditions.

  描述了一种催化协议，该协议利用水作为正式氢化物源可靠地预测和控制 CO2 的位点选择性掺入到各种不饱和烃中。该平台为在温和条件下催化重新利用三种丰富的正交原料提供了机会。
• Process for preparing alpha-aromatic group substituted alkanoic acids or esters thereof
  申请人：SYNTEX PHARMACEUTICALS INTERNATIONAL LIMITED

  公开号：EP0048136A2

  公开（公告）日：1982-03-24

  A process for preparing an alpha-aromatic group substituted alkanoic acid or its ester of the general formula wherein Ar represents an aromatic group and R' represents a hydrogen atom or a saturated aliphatic group, or Ar and R1 may form a condensed ring together with the carbon atom to which they are bonded; and R2 represents a hydrogen atom, an alkyl group, or a hydroxyalkyl group. characterized in that an alpha-sulfonyloxyketone acetal of the general formula wherein R3 and R4, independently from each other, represent an alkyl group, or taken together, represent an alkylene group; R5 represents a substituted or unsubstituted alkyl group or an aromatic group; and Ar and R1 are as defined above, is hydrolyzed, or treated with an agent having affinity for oxygen: and novel intermediate compounds of the general formula (II) used in aforesaid process.

  一种通式为α-芳香族取代的烷酸或其酯的制备方法 其中 Ar 代表芳香族基团，R'代表氢原子或饱和脂肪族基团，或 Ar 和 R1 可与它们所键合的碳原子一起形成缩合环；R2 代表氢原子、烷基或羟烷基。 其特征在于通式的α-磺酰氧基酮缩醛 其中 R3 和 R4 独立地代表一个烷基，或合在一起代表一个亚烷基；R5 代表一个取代或未取代的烷基或芳香基；Ar 和 R1 如上所定义。
• Optically active 1-aromatic-group-substituted-1-alkanones and methods for their manufacture
  申请人：SYNTEX PHARMACEUTICALS INTERNATIONAL LIMITED

  公开号：EP0067698A2

  公开（公告）日：1982-12-22

  A manufacturing method is described for the preparation of optically active 1-aromatic-group-substituted-l-alkanones of the formula wherein Ar is an atomic group, X is hydrogen or sulfonyloxy and R is a saturated aliphatic group. An optically active alkane acid halide of the formula wherein Y is halogen, is allowed to react with an aromatic compound in the presence of a Lewis acid. The optically active 1-aromatic-group-substituted-1-alkanones are useful intermediates in the preparation of optically active alpha-arylalkanoic acids, which are useful as pharmaceutical, e.g. anti-inflammatory, analgesic and anti-pyretic, agents and as insecticidal agents.

  本发明描述了一种制备光学活性 1-芳香族基团取代-l-烷酮的生产方法，其式为 其中 Ar 为原子团，X 为氢或磺酰氧基，R 为饱和脂肪族。式中 Y 为卤素的光学活性烷酸卤化物 式中 Y 为卤素，在路易斯酸存在下与芳香族化合物反应。具有光学活性的 1-芳香基取代-1-烷酮是制备具有光学活性的 α-芳基烷酸的有用中间体，可用作药物，如消炎、镇痛、解热和杀虫剂。
• Alpha-hydroxyketone acetals
  申请人：SYNTEX PHARMACEUTICALS INTERNATIONAL LIMITED

  公开号：EP0151702A2

  公开（公告）日：1985-08-21

  Alpha-hydroxyketone acetals of the formula: wherein Ar represents an aromatic group, R1 represents a hydrogen atom or a saturated aliphatic group, or Ar and R' form a condensed ring together with the carbon atom to which they are bonded, and R3 and R4 independently represent alkyl groups or together represent an alkylene group, subject to the proviso that Ar does not represent phenyl or 4-chlorophenyl when R' is a hydrogen atom. The acetals (VI) can be converted into alpha-sulfonyloxyketone acetals and thence into alpha-aromatic group substituted alkanoic acids or esters.

  式中：Ar 代表芳香族基团，R1 代表氢原子或饱和脂肪族基团，或 Ar 和 R' 与其键合的碳原子一起形成缩合环，R3 和 R4 独立地代表烷基或一起代表亚烷基，但 R' 为氢原子时，Ar 不代表苯基或 4-氯苯基。 缩醛 (VI) 可转化为α-磺酰氧基酮缩醛，然后转化为α-芳香族基团取代的烷酸或酯。
• TSUCHIHASHI, GEN-ICHI;KITAJIMA, KOJI;MITAMURA, SHUICHI, TETRAHEDRON LETT., 1981, 22, N 43, 4305-4308
  作者：TSUCHIHASHI, GEN-ICHI、KITAJIMA, KOJI、MITAMURA, SHUICHI

  DOI：——

  日期：——