4-(2-fluoroethoxy)-3-methoxybenzaldehyde | 914394-64-2

• 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: 4-(2-fluoroethoxy)-3-methoxybenzaldehyde
• CAS: 914394-64-2
• 化学式: C₁₀H₁₁FO₃
• 分子量: 198.194
• InChiKey: FTTUUCNBOJJIGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-fluoroethoxy)-3-methoxybenzaldehyde 在 lithium aluminium tetrahydride 、 ammonium acetate 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 2-(3-fluoro-4-methoxyphenyl)-N-(2-(4-(2-fluoroethoxy)-3-methoxyphenyl)-2-methoxyethyl)acetamide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A

  摘要：

  A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A, the binding affinities (IC50 value) for PDE3A and PDE3B were tested. Of these analogues, compounds 6a, 6b, 6n, 8b, 8c and 11 displayed relatively higher PDE10A potency with IC50 value in the range of 28-60 nM. The most potent compound 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline (8c) has the IC50 value of 28 +/- 1.2 nM for PDE10A, 2200 +/- 437 nM for PDE3A and 2520 +/- 210 nM for PDE3B. Compared to papaverine, compound 8c displayed similar PDE10A potency but improved selectivity to PDE10A versus PDE3A and PDE3B. To identify high potent PDE10A inhibitor, further optimization of the structures of these analogues is necessary. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.072
• 作为产物：
  描述：

  4-methylbenzenesulfonic acid [(4-formyl-2-methoxyphenoxy)ethyl] ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以74%的产率得到4-(2-fluoroethoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  Curcumin and Dehydrozingerone Derivatives:  Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging^†

  摘要：

  Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (A beta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K-i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for A beta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [F-18]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [F-18]8 is metabolically stable in the brain. These results suggest that [F-18]8 is a suitable radioligand for A beta plaque imaging.

  DOI：

  10.1021/jm0607193

文献信息

• Synthesis and characterization of ¹⁸F-labeled hydrazinocurcumin derivatives for tumor imaging
  作者：Sarah Shin、Hyun-Jung Koo、Iljung Lee、Yearn Seong Choe、Joon Young Choi、Kyung-Han Lee、Byung-Tae Kim

  DOI：10.1039/c5ra15380h

  日期：——

  Radiolabeled hydrazinocurcumin derivatives, [¹⁸F]1 and [¹⁸F]2 were synthesized and both radioligands were resistant to reductive metabolism. MicroPET images of C6 glioma xenografted mice showed high tumor uptake and retention of [¹⁸F]2.

  放射标记的肼基姜黄素衍生物，[¹⁸F]1 和 [¹⁸F]2 已合成，两种放射配体都对还原代谢具有抵抗性。C6胶质瘤移植小鼠的MicroPET图像显示 [¹⁸F]2 的肿瘤摄取和滞留高。
• IMIDAZOL (1,2-A)PYRIDINES AND RELATED COMPOUNDS WITH ACTIVITY AT CANNABINOID CB2 RECEPTORS
  申请人：Olsson Roger

  公开号：US20110206607A1

  公开（公告）日：2011-08-25

  Disclosed herein are compounds of Formula (I), or a pharmaceutically acceptable salt, ester, amide, thereof; and methods of modulating the activity of a cannabinoid CB2 receptor comprising contacting a compound of Formula I with the cannabinoid CB2 receptor. Also disclosed are methods of imaging of a tissue by positron emission tomography, the method comprising administering to the subject a compound of Formula I, wherein the compound comprises a radioisotope. Also disclosed are methods of measuring the relative concentration of cannabinoid CB2 receptors in tissue of a subject, by using a compound of Formula I which comprises a radioisotope. In addition, method of diagnosing a disorder in a subject are disclosed.

  本文公开了I式化合物，或其药学上可接受的盐、酯、酰胺等；以及调节大麻素CB2受体活性的方法，包括将I式化合物与大麻素CB2受体接触。还公开了通过正电子发射断层扫描成像组织的方法，该方法包括向受试者注射I式化合物，其中该化合物包含放射性同位素。还公开了通过使用含有放射性同位素的I式化合物来测量受试者组织中大麻素CB2受体的相对浓度的方法。此外，还公开了一种诊断受试者疾病的方法。
• Discovery of a dopamine D4 selective PET ligand candidate taking advantage of a click chemistry based REM linker
  作者：Rainer Tietze、Stefan Löber、Harald Hübner、Peter Gmeiner、Torsten Kuwert、Olaf Prante

  DOI：10.1016/j.bmcl.2007.12.026

  日期：2008.2

  Employing D4 selective azaindoles as lead compounds, a focused library of the carbocyclic arene bioisosteres 1 was synthesized when we took advantage of the click chemistry derived triazolylmethyl acrylate resin 2. Ligand binding assays on monoaminergic GPCRs led to SARs that indicated further lead structure optimizations when the attachment of alkoxy substituents provided both an improvement of the biological properties and the opportunity to introduce F-18 as a radioisotope. Finally, radiosynthesis resulted in formation of the radioligand [F-18]7h that showed optimal logD(7.4) of 2.8 and was determined to be highly stable in human serum. Thus, [F-18]7h represents a promising dopamine D4 selective radioligand for positron emission tomography (PET). (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of 1-(4-[18F]fluoroethyl)-7-(4′-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging
  作者：Iljung Lee、Jehoon Yang、Jung Hee Lee、Yearn Seong Choe

  DOI：10.1016/j.bmcl.2011.08.003

  日期：2011.10

  Alzheimer's disease is characterized by the accumulation of beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [F-18]fluoropropylcurcumin ([F-18]FP-curcumin), which demonstrated excellent binding affinity (K-i = 0.07 nM) for A beta(1-40) aggregates and good pharmacokinetics in normal mouse brains. However, its initial brain uptake was poor (0.52% ID/g at 2 min post-injection). Therefore, in the present study, fluorine-substituted 4,4'-bissubstituted or pegylated curcumin derivatives were synthesized and evaluated. Their binding affinities for A beta(1-42) aggregates were measured and 1-(4-fluoroethyl)-7-(4'-methyl) curcumin (1) had the highest binding affinity (K-i = 2.12 nM). Fluorescence staining of Tg APP/PS-1 mouse brain sections demonstrated high and specific labeling of A beta plaques by 1 in the cortex region, which was confirmed with thioflavin-S staining of the same spots in the adjacent brain sections. Radioligand [F-18]1 was found to have an appropriate partition coefficient (logP(o/w) = 2.40), and its tissue distribution in normal mice demonstrated improved brain permeability (1.44% ID/g at 2 min post-injection) compared to that of [F-18]FP-curcumin by a factor of 2.8 and fast wash-out from mouse brains (0.45% ID/g at 30 min post-injection). These results suggest that [F-18]1 may hold promise as a PET radioligand for A beta plaque imaging. (C) 2011 Elsevier Ltd. All rights reserved.
• [EN] IMIDAZOL [1,2-A] PYRIDINES AND RELATED COMPOUNDS WITH ACTIVITY AT CANNABINOID CB2 RECEPTORS<br/>[FR] IMIDAZOLE [1,2-A] PYRIDINES ET COMPOSÉS PRÉSENTANT UNE ACTIVITÉ AU NIVEAU DES RÉCEPTEURS CB2 CANNABINOÏDES
  申请人：ACADIA PHARM INC

  公开号：WO2008141239A1

  公开（公告）日：2008-11-20

  [EN] Disclosed are compounds of Formula (I) or Formula (II) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof; and methods of modulating the activity of a cannabinoid CB2 receptor comprising contacting a compound of Formula (I) or Formula (II) with the cannabinoid CB2 receptor. Said compounds are useful in the treatment of various condition and disorders such as pain, and neurodegenerative disorders.
  [FR] L'invention concerne des composés de formule (I) ou de formule (II) ou un sel, un ester, un amide ou un promédicament de ceux-ci pharmaceutiquement acceptable. Elle concerne également des procédés de modulation de l'activité d'un récepteur CB2 cannabinoïde qui consiste à mettre en contact un composé de formule (I) ou de formule (II) avec un récepteur CB2 cannabinoïde. Ces composés sont utiles dans le traitement de divers troubles et maladies tels que la douleur, et des maladies neurodégénératives.