(±)-methyl 2-[4-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluorophenyl]propanoate

• 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-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluorophenyl]propanoate
• 英文别名: methyl 2-[4-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluoro-phenyl]propanoate；methyl 2-[4-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluorophenyl]propanoate
• 化学式: C₂₃H₂₆FNO₄
• 分子量: 399.462
• InChiKey: JQGLJGXWAKZKIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.19
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (±)-methyl 2-[4-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluorophenyl]propanoate 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以26%的产率得到2-[4-[3-(cyclohexyl-carbamoyloxy)phenyl]-3-fluoro-phenyl]propanoic acid
  参考文献：
  名称：

  [EN] MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF
  [FR] INHIBITEURS DE FAAH ET DE COX MULTICIBLES ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  该发明提供了一种新型的多靶点抑制剂，用于抑制酶脂肪酸酰胺水解酶（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碳酸酯基团，并且在联苯核心的B环的邻位具有卤素。该发明还涉及多靶点抑制剂在特定情况下用于预防和治疗癌症的治疗应用。

  公开号：

  WO2014023643A1
• 作为产物：
  描述：

  methyl 2-(3-fluoro-4-iodo-phenyl)propanoate 在 4-二甲氨基吡啶 、 palladium diacetate 、 potassium carbonate 作用下， 以 乙二醇甲醚 、 水 、 乙腈 为溶剂， 反应 30.0h， 生成 (±)-methyl 2-[4-[3-(cyclohexylcarbamoyloxy)phenyl]-3-fluorophenyl]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

• MULTITARGET FAAH AND COX INHIBITORS AND THERAPEUTICAL USES THEREOF
  申请人：FONDAZIONE INSTITUTO ITALIANO DI TECHNOLOGIA

  公开号：US20150203447A1

  公开（公告）日：2015-07-23

  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. Also concerns the therapeutical application of the multitarget inhibitors, in particular, in the prevention and treatment of cancer.

  多靶点抑制剂对酶脂肪酰胺水解酶（FAAH）、环氧合酶-1（COX-1）和/或环氧合酶-2（COX-2）具有特定的羧酸酯基团，位于取代联苯核的A环的间位或邻位，并且在联苯核的B环的邻位含有卤素。还涉及多靶点抑制剂的治疗应用，特别是在预防和治疗癌症方面。
• US9630914B2
  申请人：——

  公开号：US9630914B2

  公开（公告）日：2017-04-25