1228664-31-0

Upstream product

• 54245-42-0 [11C]methyl iodide 
• 61566-33-4 p-isobutylphenylacetic acid methyl ester 

Downstream Products

• 1228664-37-6 2-(4-isobutylphenyl)-[3-⁽¹¹⁾C]propionic acid 
• 1311284-72-6 ⁽¹¹⁾C-(S)-ibuprofen 
• 1311284-71-5 ⁽¹¹⁾C-(R)-ibuprofen 

Relevant academic research and scientific papers

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

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 11C-labeling of ibuprofen for chiral separation via the TBAF-promoted α-[ 11C]methylation was achieved by using DMSO rather than THF as the reaction solvent. The robust production of the radiochemically labile 11C-labeled ibuprofen ester was realized by the protective effect of DMSO on radiolysis. After intravenous injection of each enantiomer of [ 11C]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.

Tetrabutylammonium fluoride-promoted α-[11C]methylation of α-arylesters: A simple and robust method for the preparation of 11C-labeled ibuprofen

Tetrabutylammonium fluoride-promoted α-[11C]methylation of α-arlylesters was developed. The method was amenable to the remote-controlled synthesis of 11C-labeled ibuprofen.

General method for the C-labeling of 2-arylpropionic acids and their esters: Construction of a PET tracer library for a study of biological events involved in COXs expression

Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2-arylpropionic acids that have a common methylated structure, particularly among nonsteroidal antiinflammatory drugs (NSAIDs). Thus, we developed a novel 11C-radiolabeling methodology based on rapid C[11C] methylation by the reaction of [11C]CH3I with enolate intermediates generated from the 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 useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)-induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [ 11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C-labeling of 2-arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.