Kügler F, Sihver W, Ermert J, Hübner H, Gmeiner P, Prante O, Coenen HH (2011)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2011
Original Authors: Kugler F., Sihver W., Ermert J., Hubner H., Gmeiner P., Prante O., Coenen H.H.
Publisher: American Chemical Society
Book Volume: 54
Pages Range: 8343-8352
Journal Issue: 24
DOI: 10.1021/jm200762g
Derivatization of the putative neuroleptic 1-(2,3-dihydrobenzo[1,4]dioxin- 6-yl)-4-(4-fluorobenzyl)-piperazine (3a) led to a series of new dopamine receptor D ligands displaying high affinity (K = 1.1-15 nM) and D /D subtype selectivities of about 800-6700. These ligands were labeled with the short-lived positron emitter fluorine-18 and analyzed for their potential application for imaging studies by positron emission tomography (PET). In vitro autoradio-graphy was used to determine their nonspecific binding behavior as a result of their structural and thus physicochem-ical properties. The biodistribution, in vivo stability, and brain uptake of the most promising D radioligand candidate were determined. This proved to be 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-((6- fluoropyridin-3-yl)methyl)piperazine ([ F]3d), which revealed an excellent binding pattern with a high selectivity and limited nonspecific binding in vitro. This analogue also exhibited a high stability and an extremely high brain uptake in vivo with specific binding in hippocampus, cortex, colliculus, and cerebellum as determined by ex vivo autoradiography. Thus, [ F]3d appears as a suitable D radioligand for in vivo imaging, encouraging continued evaluation by PET studies. (Figure presented) © 2011 American Chemical Society.
APA:
Kügler, F., Sihver, W., Ermert, J., Hübner, H., Gmeiner, P., Prante, O., & Coenen, H.H. (2011). Evaluation of 18F-labeled benzodioxine piperazine-based dopamine D4 receptor ligands: Lipophilicity as a determinate of nonspecific binding. Journal of Medicinal Chemistry, 54(24), 8343-8352. https://doi.org/10.1021/jm200762g
MLA:
Kügler, Fabian, et al. "Evaluation of 18F-labeled benzodioxine piperazine-based dopamine D4 receptor ligands: Lipophilicity as a determinate of nonspecific binding." Journal of Medicinal Chemistry 54.24 (2011): 8343-8352.
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