N-(4-Methoxy-benzyl)-N-(2-phenoxy-phenyl)-acetamide

• 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: N-(4-Methoxy-benzyl)-N-(2-phenoxy-phenyl)-acetamide
• 英文别名: N-[(4-methoxyphenyl)methyl]-N-(2-phenoxyphenyl)acetamide
• 化学式: C₂₂H₂₁NO₃
• 分子量: 347.414
• InChiKey: BPEBAEHCDMRRBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基二苯醚 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(4-Methoxy-benzyl)-N-(2-phenoxy-phenyl)-acetamide
  参考文献：
  名称：

  Design, synthesis and structure–affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands

  摘要：

  Since the peripheral benzodiazepine receptor (PBR) has been primarily found as a high-affinity binding site for diazepam in rat kidney, numerous studies of it have been performed. However, the physiological role and functions of PBR have not been fully elucidated. Currently, we presented the pharmacological profile of two high and selective PBR ligands, N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)acetamide (7-096, DAA1106) (PBR: IC50 = 0.28 nM) and N-(4-chloro-2-phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (7-099, DAA1097) (PBR: IC50=0.92 nM). The compounds are aryloxyanilide derivatives, and identified with known PBR ligands such as benzodiazepine (1, Ro5-4864), isoquinoline (2, PK11195), imidazopyridine (3, Alpidem), and indole (5, FGIN-1-27) derivatives. The aryloxyanilide derivatives, which have been derived by opening the diazepine ring of 1, are a novel class as PBR ligands and have exhibited high and selective affinity for peripheral benzodiazepine receptors (PBRs). These novel derivatives would be useful for exploring the functions of PBR. In this paper, the design, synthesis and structure-affinity relationships of aryloxyanilide derivatives are described. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.050

文献信息

• [EN] CARBON-ISOTOPE MONOXIDE LABELING OF DAA1106 AND ITS ANALOGUES TO BE USED AS TRACERS FOR A PERIPHERAL TYPE BENZODIAZEPINE BINDING SITE<br/>[FR] MARQUAGE PAR MONOXYDE D'ISOTOPE DE CARBONE DE DAA1106 ET DE SES ANALOGUES EN VUE DE LEUR UTILISATION COMME INDICATEURS POUR UN SITE DE LIAISON DE BENZODIAZEPINE DE TYPE PERIPHERIQUE
  申请人：GE HEALTHCARE LTD

  公开号：WO2007036785A2

  公开（公告）日：2007-04-05

  [EN] A potent and selective ligand for peripheral benzodiazepine receptor (PBR), N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide or DAA1106 and eight structurally related analogues were labelled with ¹¹C at carbonyl position of the molecule using a low concentration of [¹¹C]carbon monoxide and micro autoclave techniques. Palladium mediated carbonylation using tetrakis(triphenylphosphine)palladium, methyl iodide or iodobenzene and different amines was employed in the synthesis. The ¹¹C-labelled products were obtained with 15-45% decay-corrected radiochemical yields. Specific radioactivity was determined for the compound [carbonyl-¹¹C]DAA1106 to investigate the possibility to obtain the high specific radioactivity for the compounds prepared using this method. The obtained specific radioactivity was 121 GBq/µmol, 36 min after a bombardment of 10 µAh. Synthetic routes for the preparation of precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl-¹¹C]DAA1106 and analogues. Accordingly, the synthetic routes for the preparation of precursor amines and reference compounds are provided. A kit claim and a method of use claim for a PET study comprising an effective amount of carbon-isotope labeled compound and pharmaceutically acceptable salts and solvates thereof are also provided.
  [FR] Selon l'invention, un ligand puissant et sélectif pour un récepteur de benzodiazépine périphérique (PBR), N-(2,5-diméthoxybenzyl)-N-(5-fluoro-2-phénoxyphényl)acétamide ou DAA1106, et huit analogues structuralement associés ont été marqués avec ¹¹C en position carbonyle de la molécule au moyen d'une faible concentration de monoxyde de [¹¹C]carbone et de techniques en micro-autoclave. Une carbonylation médiée par palladium faisant intervenir du tétrakis(triphénylphosphine)palladium, de l'iodure de méthyle ou de l'iodobenzène et différentes amines a été utilisée dans la synthèse. Les produits à marquage ¹¹C ont été obtenus avec des rendements radiochimiques corrigés en désintégration radioactive de 15 à 45 %. La radioactivité spécifique a été déterminée pour le composé [carbonyl-¹¹C]DAA1106 en vue de l'exploration de la possibilité d'obtenir la radioactivité spécifique élevée pour les composés préparés au moyen de ce procédé. La radioactivité spécifique obtenue était de 121 GBq/µmol 36 minute après un bombardement de 10 µAh. Des voies de synthèse pour la préparation de précurseurs et de composés de référence ont également été mises au point. L'approche présentée est un nouveau procédé pour la synthèse de [carbonyl-¹¹C]DAA1106 et d'analogues. Par conséquent, l'invention concerne les voies de synthèse pour la préparation d'amines précurseurs et de composés de référence. Elle concerne en outre une trousse et un procédé d'utilisation de cette trousse pour une étude PET, ladite trousse comprenant une dose efficace de composé marqué par isotope de carbone et des sels et des solvates pharmaceutiquement acceptables correspondants.
• Design, synthesis and structure–affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands
  作者：Taketoshi Okubo、Ryoko Yoshikawa、Shigeyuki Chaki、Shigeru Okuyama、Atsuro Nakazato

  DOI：10.1016/j.bmc.2003.10.050

  日期：2004.1

  Since the peripheral benzodiazepine receptor (PBR) has been primarily found as a high-affinity binding site for diazepam in rat kidney, numerous studies of it have been performed. However, the physiological role and functions of PBR have not been fully elucidated. Currently, we presented the pharmacological profile of two high and selective PBR ligands, N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)acetamide (7-096, DAA1106) (PBR: IC50 = 0.28 nM) and N-(4-chloro-2-phenoxyphenyl)-N-(2-isopropoxybenzyl)acetamide (7-099, DAA1097) (PBR: IC50=0.92 nM). The compounds are aryloxyanilide derivatives, and identified with known PBR ligands such as benzodiazepine (1, Ro5-4864), isoquinoline (2, PK11195), imidazopyridine (3, Alpidem), and indole (5, FGIN-1-27) derivatives. The aryloxyanilide derivatives, which have been derived by opening the diazepine ring of 1, are a novel class as PBR ligands and have exhibited high and selective affinity for peripheral benzodiazepine receptors (PBRs). These novel derivatives would be useful for exploring the functions of PBR. In this paper, the design, synthesis and structure-affinity relationships of aryloxyanilide derivatives are described. (C) 2003 Elsevier Ltd. All rights reserved.