methyl 2-(4-amino-3-fluoro-phenyl)propanoate | 90500-55-3

• 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-amino-3-fluoro-phenyl)propanoate
• 英文别名: Methyl 2-(4-amino-3-fluorophenyl)propanoate
• CAS: 90500-55-3
• 化学式: C₁₀H₁₂FNO₂
• 分子量: 197.209
• InChiKey: AZNANEAJNFHWED-UHFFFAOYSA-N

物化性质

• 沸点：
  140-143 °C(Press: 9 Torr)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	2-(4-amino-3-fluorophenyl)propionic acid	81937-33-9	C9H10FNO2	183.182
  ——	(±)-methyl 2-(4-nitro-3-fluorophenyl)propanoate	86790-39-8	C10H10FNO4	227.192
  ——	2-(3-fluoro-4-nitro-phenyl)propanoic acid	——	C9H8FNO4	213.165

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	Methyl 2-(4-ethenyl-3-fluorophenyl)propanoate	1402585-80-1	C12H13FO2	208.232
  ——	2-(4-cyano-3-fluorophenyl)propanoic acid	1402585-20-9	C10H8FNO2	193.177
  乙基6,7-二甲氧基-3-甲基-4-氧代-1-(3,4,5-三甲氧基苯基)-1,2,3,4-四氢-2-萘l烯羧酸酯	methyl 2-(2-fluoro-4-biphenylyl)propionate	66202-86-6	C16H15FO2	258.292
  ——	2-(4-Ethenyl-3-fluorophenyl)propanoic acid	1402585-81-2	C11H11FO2	194.206
  ——	methyl 2-[4-(3-aminophenyl)-3-fluoro-phenyl]propanoate	1557065-63-0	C16H16FNO2	273.307
  ——	methyl 2-(2-fluoro-4'-hydroxybiphenyl-4-yl)propanoate	482294-50-8	C16H15FO3	274.292
  ——	methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]propanoate	1557065-61-8	C16H15FO3	274.292
  (R)-2-氟比洛芬 氟比洛芬	(R)-flurbiprofen	51543-40-9	C15H13FO2	244.265
  艾氟洛芬	(S)-(+)-flurbiprofen	51543-39-6	C15H13FO2	244.265
  ——	methyl 2-[3-fluoro-4-(2-hydroxyphenyl)phenyl]propanoate	1557065-57-2	C16H15FO3	274.292

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-amino-3-fluoro-phenyl)propanoate 在 盐酸 、 4-二甲氨基吡啶 、 水 、 palladium diacetate 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇甲醚 、 水 、 甲苯 为溶剂， 反应 60.5h， 生成 (R)-2-氟比洛芬 氟比洛芬
  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 钯 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以to obtain methyl 2-(4-amino-3-fluorophenyl)propanoate的产率得到methyl 2-(4-amino-3-fluoro-phenyl)propanoate
  参考文献：
  名称：

  Aryl or N-heteroaryl Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands

  摘要：

  本发明涉及芳基或N-杂环芳基取代的甲磺酰胺衍生物作为vanilloid受体配体，含有这些化合物的制药组合物以及这些化合物用于治疗和/或预防疼痛和其他疾病和/或紊乱的用途。

  公开号：

  US20130079377A1

文献信息

• [EN] ARYL OR N-HETEROARYL SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE MÉTHANESULFONAMIDE SUBSTITUÉS PAR UN ARYLE OU N-HÉTÉROARYLE EN TANT QUE LIGANDS D'UN RÉCEPTEUR VANILLOÏDE
  申请人：GRUENENTHAL GMBH

  公开号：WO2013045447A1

  公开（公告）日：2013-04-04

  The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives of Formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

  这项发明涉及公式（I）的芳基或N-杂环芳基取代的甲磺酰胺衍生物作为辣椒素受体配体，以及含有这些化合物的药物组合物，还涉及这些化合物用于治疗和/或预防疼痛以及其他疾病和/或紊乱。
• [EN] SUBSTITUTED PYRAZOLYL-BASED CARBOXAMIDE AND UREA DERIVATIVES BEARING A PHENYL MOIETY SUBSTITUTED WITH AN O-CONTAINING GROUP AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE ET D'URÉE À BASE DE PYRAZOLYLE SUBSTITUÉ PORTANT UN FRAGMENT PHÉNYLE REMPLACÉ PAR UN GROUPE CONTENANT O COMME LIGANDS DES RÉCEPTEURS VANILLOÏDES
  申请人：GRUENENTHAL GMBH

  公开号：WO2013068461A1

  公开（公告）日：2013-05-16

  The invention relates to substituted pyrazolyl-based carboxamide and urea derivatives of formula (Q) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

  这项发明涉及以式(Q)的取代吡唑基羧酰胺和脲衍生物作为辣椒素受体配体，以及含有这些化合物的药物组合物，还涉及这些化合物用于治疗和/或预防疼痛以及其他疾病和/或紊乱。
• Process for preparing biaryl compounds via coupling of an arylamine with
  申请人：Biaschim S.p.A.

  公开号：US04542233A1

  公开（公告）日：1985-09-17

  Improvement in the process for preparing biaryl compounds via coupling of an arylamine with an arene in the presence of a nitrite, an acid and copper metal or a derivative thereof; the improvement is consisting in adding to the reaction mixture a trialkylorthoformate. The process may be used for preparing drugs such as Flurbiprofen and Xenbucin or intermediate compounds particularly useful for preparing Flurbiprofen, Flufenisal, Chlordimorin, Xenbucin, Xenysalate, Xenyhexenic acid and the like.

  通过在亚硝酸盐、酸和铜金属或其衍生物存在下，通过芳胺与芳烃偶联制备双芳基化合物的过程中的改进；改进在于向反应混合物中加入三烷基邻甲酸酯。该过程可用于制备药物，如氟比派芬和西恩布辛，或特别用于制备氟比派芬、氟氟尼萨、氯地莫林、西恩布辛、西恩沙拉特、西恩己烯酸等中间化合物。
• [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。
• 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。