N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧基苯基)乙酰胺 | 220551-92-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧基苯基)乙酰胺
• 英文名称: DAA 1106
• 英文别名: N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide；N-[(2,5-dimethoxyphenyl)methyl]-N-(5-fluoro-2-phenoxyphenyl)acetamide
• CAS: 220551-92-8
• 化学式: C₂₃H₂₂FNO₄
• 分子量: 395.43
• InChiKey: DCRZYADKQRHHSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-fluoro-2-nitro-1-phenoxybenzene 在 platinum(IV) oxide 氢气 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧基苯基)乙酰胺
  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

• Synthesis ofN-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)[carbonyl-11C]acetamide ([carbonyl-11C]DAA1106) and analogues using [11C]carbon monoxide and palladium(0) complex
  作者：Obaidur Rahman、Bengt Långström

  DOI：10.1002/jlcr.1437

  日期：2007.11

  N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), a potent and selective ligand for peripheral benzodiazepine receptor, and eight structurally related analogues were labelled with 11C at the carbonyl position using a low concentration of [11C]carbon monoxide and the micro-autoclave technique. A combinatorial approach was applied to synthesize the analogues using similar reaction conditions. Palladium-mediated carbonylation using tetrakis(triphenylphosphine)palladium, various amines and methyl iodide or iodobenzene was employed in the synthesis. The 11C-labelled products were obtained with 10–55% decay-corrected radiochemical yields and the final product was more than 97% pure in all cases. Specific radioactivity was determined for the compound [carbonyl-11C]DAA1106 using a single experiment and a 10-µA h bombardment. The specific radioactivity, measured 36 min after end of bombardment, was 455 GBq/µmol. Synthetic routes to the precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl-11C]DAA1106 and its analogues, and allows the formation of a library of 11C-labelled DAA1106 analogues which can be used to optimize the performance as a potential positron emission tomography tracer. Copyright © 2007 John Wiley & Sons, Ltd.

  N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧苯基)乙酰胺（DAA1106），一种强效且选择性的外周苯二氮卓受体配体，及其八个结构相关的类似物，使用低浓度的[11C]一氧化碳和微型高压釜技术在羰基位置进行了11C标记。采用组合方法，利用相似的反应条件合成了这些类似物。合成中使用了四(三苯膦)钯介导的羰基化反应，并结合了各种胺和甲基碘或碘苯。所得的11C标记产物具有10-55%的衰变校正放射化学产率，所有情况下最终产物纯度均超过97%。通过单次实验和10µA h轰击，测定了化合物[羰基-11C]DAA1106的比活度。轰击结束后36分钟测得的比活度为455 GBq/µmol。还开发了合成前体和参考化合物的路线。所提出的方法是一种新颖的[羰基-11C]DAA1106及其类似物的合成方法，并能够形成一系列11C标记的DAA1106类似物库，这些类似物可用于优化其作为潜在正电子发射断层扫描示踪剂的性能。版权所有 © 2007 John Wiley & Sons, Ltd.
• RADIOACTIVE HALOGEN-LABELED PHENYLOXYANILINE DERIVATIVES
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP1854781A1

  公开（公告）日：2007-11-14

  A radioactive halogen-labeled phenyoxyaniline derivative represented by the following formula: wherein R1 represents a group such as an alkyl group; X1, X2, X3 and X4 represent each a hydrogen atom, an alkyl group, an alkoxy group, an alkoxy group carrying 11C introduced thereinto or a radioactive halogen atom, provided that at least one of X1, X2, X3 and X4 represents an alkoxy group carrying 11C introduced thereinto or a radioactive halogen atom; which is a compound useful as a PBR ligand having a high affinity and a high selectivity. In in vitro measurement of PBR, a PBR ligand having a high affinity and a high selectivity is labeled with a radioactive halogen nuclear species so as to enable the measurement of PBR in vivo with the use of means including not only PET but also SPECT. Thus, a compound which is useful in early diagnosing, preventing and treating diseases such as Alzheimer type dementia can be obtained.

  一种放射性卤素标记的苯氧胺衍生物，其化学式如下：其中R1代表类似烷基的基团；X1、X2、X3和X4分别代表氢原子、烷基、烷氧基、携带11C的烷氧基或放射性卤素原子，至少其中之一代表携带11C的烷氧基或放射性卤素原子；该化合物作为具有高亲和力和高选择性的PBR配体而有用。在体外测量PBR时，将具有高亲和力和高选择性的PBR配体标记为放射性卤素核种，以便使用PET和SPECT等手段在体内测量PBR。因此，可以获得一种在早期诊断、预防和治疗阿尔茨海默型痴呆等疾病中有用的化合物。
• AGENTS FOR THERAPY EFFICACY MONITORING AND DEEP TISSUE IMAGING
  申请人：Bornhop J. Darryl

  公开号：US20080031823A1

  公开（公告）日：2008-02-07

  Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents.

  与近红外分子成像、体外和体内功能成像、治疗/疗效监测以及癌症和转移活动成像相关的化合物和方法。展示的化合物和方法涉及外周苯二氮平受体成像、代谢成像、细胞呼吸成像、细胞增殖成像作为包含信号剂的靶向剂。
• KIT FOR PRODUCING MOLECULAR PROBE FOR PET SCREENING FOR DRUG DISCOVERY
  申请人：Doi Hisashi

  公开号：US20110064662A1

  公开（公告）日：2011-03-17

  Disclosed is a kit for use in the production of a molecular probe for PET drug screening for the purpose of producing a compound containing a short-lived radionuclide for PET applications. Specifically disclosed is a kit comprising a compound represented by the formula (I), (II) or (III) or a salt thereof. In the formulae, X 1 , X 2 , X 3 , X 4 , X 5 and X 6 are as defined in the description.

  本发明揭示了一种用于制备PET药物筛选分子探针的试剂盒，其目的是为了生产含有短寿命放射性核素的化合物，以供PET应用。具体揭示的是一种试剂盒，包括公式（I），（II）或（III）或其盐所表示的化合物。在这些公式中，X1，X2，X3，X4，X5和X6如描述中所定义。
• DAA-PYRIDINE AS PERIPHERAL BENZODIAZEPINE RECEPTOR LIGAND FOR DIAGNOSTIC IMAGING AND PHARMACEUTICAL TREATMENT
  申请人：Lehmann Lutz

  公开号：US20110200535A1

  公开（公告）日：2011-08-18

  This invention relates to novel compounds suitable for labelling or already labelled by 18 F, methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for therapy and diagnostic imaging by positron emission tomography (PET).

  本发明涉及新的化合物，适用于标记或已被18F标记，制备这种化合物的方法，包含这种化合物的组合物，包含这种化合物或组合物的试剂盒，以及这种化合物、组合物或试剂盒在正电子发射断层扫描（PET）的治疗和诊断成像中的应用。