methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate | 1557065-61-8

• 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-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate
• 英文别名: Methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate
• CAS: 1557065-61-8
• 化学式: C₁₆H₁₅FO₃
• 分子量: 274.292
• InChiKey: RWHHORKGLKJYCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate 在 盐酸 、 4-二甲氨基吡啶 、 水 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 63.0h， 生成 2-[4-[3-(benzylcarbamoyloxy)phenyl]-3-fluoro-phenyl]propanoic acid
  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：

  (±)-methyl 2-(4-nitro-3-fluorophenyl)propanoate 在 盐酸 、 palladium 10% on activated carbon 、 甲酸铵 、 palladium diacetate 、 potassium carbonate 、 sodium nitrite 作用下， 以 甲醇 、 乙二醇甲醚 、 水 为溶剂， 反应 18.5h， 生成 methyl 2-[3-fluoro-4-(3-hydroxyphenyl)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
• 作为试剂：
  描述：

  、 methyl 2-(3-fluoro-4-iodo-phenyl)propanoate 、 3-羟基苯硼酸 在 methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate 、 乙酸乙酯 作用下， 以to afford the title compound as a white oil (2.46 g, 84%)的产率得到methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate
  参考文献：
  名称：

  MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF

  摘要：

  多靶点抑制剂，包括脂肪酸酰胺水解酶（FAAH）、环氧合酶-1（COX-1）和/或环氧合酶-2（COX-2），其在取代联苯核心的A环的间位或邻位具有特定的氨基甲酸酯基团，并且在联苯核心的B环的邻位具有卤素。此外，还涉及多靶点抑制剂的治疗应用，特别是在癌症的预防和治疗方面。

  公开号：

  US20150203447A1

文献信息

• [EN] MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF<br/>[FR] INHIBITEURS DE FAAH ET DE COX MULTICIBLES ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：FOND ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：WO2014023325A1

  公开（公告）日：2014-02-13

  The invention provides novel multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted biphenyl core and having an halogen in the ortho position of the B ring of the biphenyl core. The invention concerns also with therapeutical application of the multitarget inhibitors in particular in the prevention and treatment of cancer.

  这项发明提供了新型的多靶点酶抑制剂，针对脂肪酸酰胺水解酶（FAAH）、环氧合酶-1（COX-1）和/或环氧合酶-2（COX-2），在取代联苯核心的A环的间位或邻位具有特定的氨甲酸酯基团，并在B环的邻位具有卤素。该发明还涉及这些多靶点抑制剂在特定的癌症预防和治疗中的治疗应用。
• US9630914B2
  申请人：——

  公开号：US9630914B2

  公开（公告）日：2017-04-25