3857-04-3Relevant articles and documents
Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester
Nebel, Natascha,Maschauer, Simone,Hocke, Carsten,Hübner, Harald,Gmeiner, Peter,Prante, Olaf
, p. 48 - 53 (2016)
There is still no efficient fluorine-18-labeled dopamine D3 subtype selective receptor ligand for studies with positron emission tomography. We aim at improving the D3 selectivity and hydrophilicity of a candidate ligand by changing the substitution pattern to a 2,3-dichlorophenylpiperazine and hydroxylation of the butyl chain. The compound [18F]3 exhibited D3 affinity of Ki = 3.6 nM, increased subtype selectivity (Ki(D2/D3) = 60), and low affinity to 5-HT1A and α1 receptors (Ki (5-HT1A/D3) = 34; Ki (α1/D3) = 100). The two-step radiosynthesis was optimized for analog [18F]4 by reducing the necessary concentration of the precursor amine (57 mM), which reacted with [18F]fluorophenylazocarboxylic tert-butylester under basic conditions. The optimization of the base (Cs 2CO3, 23 mM) and the adjustment of reaction temperature led to the radiochemical yield of 63% after 5 min at 35C. The optimized reaction conditions were transferred on to the synthesis of [18F]3 with an overall non-decay corrected yield of 8-12% in a specific activity of 32-102 GBq/μmol after a total synthesis time of 30-35 min. This provides a D 3 radioligand candidate with improved attributes concerning selectivity and radiosynthesis for further preclinical studies.
Chemoselective Radiosyntheses of Electron-Rich [18F]Fluoroarenes from Aryl(2,4,6-trimethoxyphenyl)iodonium Tosylates
Kwon, Young-Do,Son, Jeongmin,Chun, Joong-Hyun
, p. 3678 - 3686 (2019/03/11)
Hypervalent diaryliodonium salts have been used to produce various [18F]fluoroarenes. The iodonium salt approach as a labeling precursor has been established to equally afford complex 18F-fluorinated molecules. Because of the inheren
Crystal Structures of Diaryliodonium Fluorides and Their Implications for Fluorination Mechanisms
Lee, Yong-Sok,Chun, Joong-Hyun,Hodo??ek, Milan,Pike, Victor W.
, p. 4353 - 4363 (2017/04/03)
The radiofluorination of diaryliodonium salts is of value for producing radiotracers for positron emission tomography. We report crystal structures for two diaryliodonium fluorides. Whereas diphenyliodonium fluoride (1 a) exists as a tetramer bridged by four fluoride ions, 2-methylphenyl(phenyl)iodonium fluoride (2 a) forms a fluoride-bridged dimer that is further halogen bonded to two other monomers. We discuss the topological relationships between the two and their implications for fluorination in solution. Both radiofluorination and NMR spectroscopy show that thermolysis of 2 a gives 2-fluorotoluene and fluorobenzene in a 2 to 1 ratio that is in good agreement with the ratio observed from the radiofluorination of 2-methylphenyl(phenyl)iodonium chloride (2 b). The constancy of the product ratio affirms that the fluorinations occur via the same two rapidly interconverting transition states whose energy difference dictates chemoselectivity. From quantum chemical studies with density functional theory we attribute the “ortho-effect” to the favorable electrostatic interaction between the incoming fluoride and the o-methyl in the transition state. By utilizing the crystal structures of 1 a and 2 a, the mechanisms of fluoroarene formation from diaryliodonium fluorides in their monomeric, homodimeric, heterodimeric, and tetrameric states were also investigated. We propose that oligomerization energy dictates whether the fluorination occurs through a monomeric or an oligomeric pathway.
