[11C]-ibuprofen methyl ester | 1228664-31-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [11C]-ibuprofen methyl ester
• 英文别名: methyl 2-[4-(2-methylpropyl)phenyl](311C)propanoate
• CAS: 1228664-31-0
• 化学式: C₁₄H₂₀O₂
• 分子量: 219.301
• InChiKey: YNZYUHPFNYBBFF-KTXUZGJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [11C]-ibuprofen methyl ester 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.02h， 生成 [11C]-ibuprofen
  参考文献：
  名称：

  2-芳基丙酸及其酯的11C标签通用方法：构建PET示踪剂库，用于研究涉及COXs表达的生物事件

  摘要：

  环氧合酶（COX）是前列腺素生物合成中的关键酶，可调节多种生物学功能，例如疼痛，发烧等。为了通过正电子发射断层扫描（PET）进行体内COX成像，我们开发了一种将11 C放射性核素掺入各种具有共同甲基化结构的2-芳基丙酸中的方法，尤其是在非甾体类抗炎药（NSAIDs）中。因此，我们在碱性条件下通过[ 11 C] CH 3 I与相应酯生成的烯醇酸酯中间体反应，基于快速C- [ 11 C]甲基化，开发了一种新颖的11 C-放射性标记方法。一锅以上水解[ 11C]甲基化产物还可以合成所需的11 C-结合酸。我们证明了该方法在合成6种PET示踪剂，[ 11 C]布洛芬，[ 11 C]萘普生，[ 11 C]氟比洛芬，[ 11 C]芬诺洛芬，[ 11 C]酮洛芬和[ 11 C]时的效用。洛索洛芬。值得注意的是，我们发现它们的甲酯特别适合用作研究神经炎症的放射菌。对患有脂多糖（LPS）引起的脑部炎症的大鼠

  DOI：

  10.1002/chem.200903044
• 作为产物：
  描述：

  [11C]methyl iodide 、 异丁芬酸甲酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.03h， 生成 [11C]-ibuprofen methyl ester
  参考文献：
  名称：

  2-芳基丙酸及其酯的11C标签通用方法：构建PET示踪剂库，用于研究涉及COXs表达的生物事件

  摘要：

  环氧合酶（COX）是前列腺素生物合成中的关键酶，可调节多种生物学功能，例如疼痛，发烧等。为了通过正电子发射断层扫描（PET）进行体内COX成像，我们开发了一种将11 C放射性核素掺入各种具有共同甲基化结构的2-芳基丙酸中的方法，尤其是在非甾体类抗炎药（NSAIDs）中。因此，我们在碱性条件下通过[ 11 C] CH 3 I与相应酯生成的烯醇酸酯中间体反应，基于快速C- [ 11 C]甲基化，开发了一种新颖的11 C-放射性标记方法。一锅以上水解[ 11C]甲基化产物还可以合成所需的11 C-结合酸。我们证明了该方法在合成6种PET示踪剂，[ 11 C]布洛芬，[ 11 C]萘普生，[ 11 C]氟比洛芬，[ 11 C]芬诺洛芬，[ 11 C]酮洛芬和[ 11 C]时的效用。洛索洛芬。值得注意的是，我们发现它们的甲酯特别适合用作研究神经炎症的放射菌。对患有脂多糖（LPS）引起的脑部炎症的大鼠

  DOI：

  10.1002/chem.200903044

文献信息

• ISOTOPE LABELED 2-ARYLPROPIONIC ACID COMPOUNDS AND PROCESS FOR PRODUCTION OF SAME, AND MOLECULAR PROBE FOR POSITRON EMISSION TOMOGRAPHY AND METHOD FOR IMAGING OF CYCLOOXYGENASE AND THE LIKE USING SAME
  申请人：Takashima Misato

  公开号：US20120128588A1

  公开（公告）日：2012-05-24

  Disclosed are: labeled NSAIDs compounds which can be produced within a short time, can be used suitably for a PET method, and enable the imaging of cyclooxygenase-2; and a process for producing the labeled NSAIDs compounds. Specifically disclosed are isotope-labeled 2-arylpropionic acid compounds, each of which is a compound represented by general formula (1) (wherein Ar represents an aryl group which may have a substituent; R 1 represents anyone selected from 11 CH 3 , CH 2 18 F and CF 2 18 F; and R 2 represents a hydrogen atom, or an alkyl group which may have a branch, wherein a compound wherein Ar is a benzene ring, R 1 is 11 CH 3 , and R 2 is a hydrogen atom is excluded), or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.

  披露了：标记的NSAIDs化合物可以在短时间内生产，适用于PET方法，并能够成像环氧合酶-2；以及制备标记的NSAIDs化合物的方法。具体披露的是同位素标记的2-芳基丙酸化合物，每个化合物都是由通式（1）表示的化合物（其中Ar代表可能具有取代基的芳基；R1代表从11CH3、CH218F和CF218F中选择的任一种；R2代表氢原子，或可能具有支链的烷基，其中Ar为苯环，R1为11CH3，R2为氢原子的化合物被排除），或其药用可接受的盐、水合物、溶剂合物或前药。
• Tetrabutylammonium fluoride-promoted α-[11C]methylation of α-arylesters: a simple and robust method for the preparation of 11C-labeled ibuprofen
  作者：Koichi Kato、Tatsuya Kikuchi、Nobuki Nengaki、Takuya Arai、Ming-Rong Zhang

  DOI：10.1016/j.tetlet.2010.09.007

  日期：2010.11

  Tetrabutylammonium fluoride-promoted alpha-[C-11]methylation of alpha-arlylesters was developed. The method was amenable to the remote-controlled synthesis of C-11-labeled ibuprofen. (C) 2010 Elsevier Ltd. All rights reserved.
• Efficient synthesis and chiral separation of 11C-labeled ibuprofen assisted by DMSO for imaging of in vivo behavior of the individual isomers by positron emission tomography
  作者：Tatsuya Kikuchi、Maki Okada、Nobuki Nengaki、Kenji Furutsuka、Hidekatsu Wakizaka、Toshimitsu Okamura、Ming-Rong Zhang、Koichi Kato

  DOI：10.1016/j.bmc.2011.03.041

  日期：2011.5

  The pharmacological mechanisms focusing on chiral isomer of ibuprofen are not fully understood. Only the (S)-isomer of ibuprofen inhibits cyclooxygenases, which mediates the generation of prostanoids and thromboxanes. Consequently, (S)-isomers represent a major promoter of the anti-inflammatory effect, and the effects of the (R)-isomers have not been widely discussed. However, more recently, the cyclooxygenase-independent pharmacological effects of ibuprofen have been elucidated. Pharmacokinetic studies with individual isomers of ibuprofen by positron emission tomography should aid our understanding of the pharmacological mechanisms of ibuprofen. The efficient C-11-labeling of ibuprofen for chiral separation via the TBAF-promoted alpha-[C-11]methylation was achieved by using DMSO rather than THF as the reaction solvent. The robust production of the radiochemically labile C-11-labeled ibuprofen ester was realized by the protective effect of DMSO on radiolysis. After intravenous injection of each enantiomer of [C-11]ibuprofen, significantly high radioactivity was observed in the joints of arthritis mice when compared to the levels observed in normal mice. However, the high accumulation was equivalent between the enantiomers, indicating that ibuprofen is accumulated in the arthritic joints regardless of the expression of cyclooxygenases. (C) 2011 Elsevier Ltd. All rights reserved.
• General Method for the¹¹C-Labeling of 2-Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression
  作者：Misato Takashima-Hirano、Miho Shukuri、Tadayuki Takashima、Miki Goto、Yasuhiro Wada、Yasuyoshi Watanabe、Hirotaka Onoe、Hisashi Doi、Masaaki Suzuki

  DOI：10.1002/chem.200903044

  日期：2010.4.12

  corresponding esters under basic conditions. One‐pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C‐incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly

  环氧合酶（COX）是前列腺素生物合成中的关键酶，可调节多种生物学功能，例如疼痛，发烧等。为了通过正电子发射断层扫描（PET）进行体内COX成像，我们开发了一种将11 C放射性核素掺入各种具有共同甲基化结构的2-芳基丙酸中的方法，尤其是在非甾体类抗炎药（NSAIDs）中。因此，我们在碱性条件下通过[ 11 C] CH 3 I与相应酯生成的烯醇酸酯中间体反应，基于快速C- [ 11 C]甲基化，开发了一种新颖的11 C-放射性标记方法。一锅以上水解[ 11C]甲基化产物还可以合成所需的11 C-结合酸。我们证明了该方法在合成6种PET示踪剂，[ 11 C]布洛芬，[ 11 C]萘普生，[ 11 C]氟比洛芬，[ 11 C]芬诺洛芬，[ 11 C]酮洛芬和[ 11 C]时的效用。洛索洛芬。值得注意的是，我们发现它们的甲酯特别适合用作研究神经炎症的放射菌。对患有脂多糖（LPS）引起的脑部炎症的大鼠