20846-39-3Relevant academic research and scientific papers
Alcohol-supported Cu-mediated 18F-fluorination of iodonium salts under “minimalist” conditions
Orlovskaya, Victoriya V.,Modemann, Daniel J.,Kuznetsova, Olga F.,Fedorova, Olga S.,Urusova, Elizaveta A.,Kolks, Niklas,Neumaier, Bernd,Krasikova, Raisa N.,Zlatopolskiy, Boris D.
, (2019/09/09)
In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a cGMP production of imaging probes in automated synthesis modules. Herein, a novel protocol for the efficient preparation of 18F-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl)iodonium salts without the need of evaporation steps is described. Labeled aromatics were prepared in high radiochemical yields simply by heating of iodonium [18F]fluorides with the Cu-mediator in methanolic DMF. The iodonium [18F]fluorides were prepared by direct elution of 18F? from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF. The practicality of the novel method was confirmed by the racemization-free production of radiolabeled fluorophenylalanines, including hitherto unknown 3-[18F]FPhe, in 22–69% isolated radiochemical yields as well as its direct implementation into a remote-controlled synthesis unit.
LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs
Augustyn, Evan,Finke, Karissa,Zur, Arik A.,Hansen, Logan,Heeren, Nathan,Chien, Huan-Chieh,Lin, Lawrence,Giacomini, Kathleen M.,Colas, Claire,Schlessinger, Avner,Thomas, Allen A.
supporting information, p. 2616 - 2621 (2016/05/09)
The transporter protein Large-neutral Amino Acid Transporter 1 (LAT-1, SLC7A5) is responsible for transporting amino acids such as tyrosine and phenylalanine as well as thyroid hormones, and it has been exploited as a drug delivery mechanism. Recently its role in cancer has become increasingly appreciated, as it has been found to be up-regulated in many different tumor types, and its expression levels have been correlated with prognosis. Substitution at the meta position of aromatic amino acids has been reported to increase affinity for LAT-1; however, the SAR for this position has not previously been explored. Guided by newly refined computational models of the binding site, we hypothesized that groups capable of filling a hydrophobic pocket would increase binding to LAT-1, resulting in improved substrates relative to parent amino acid. Tyrosine and phenylalanine analogs substituted at the meta position with halogens, alkyl and aryl groups were synthesized and tested in cis-inhibition and trans-stimulation cell assays to determine activity. Contrary to our initial hypothesis we found that lipophilicity was correlated with diminished substrate activity and increased inhibition of the transporter. The synthesis and SAR of meta-substituted phenylalanine and tyrosine analogs is described.
