% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @INPROCEEDINGS{Willmann:865229, author = {Willmann, Michael and Ermert, Johannes and Neumaier, Bernd}, title = {{N}ovel 18{F}-labeled {D}4-receptor ligands}, reportid = {FZJ-2019-04760}, year = {2019}, abstract = {The role of the dopamine D4-receptor subtype in the development of neurodegenerative diseases such as schizophrenia has been discussed for several decades. Specific radiotracers for more detailed preclinical and clinical investigations are still missing so far. The objective of this study was to develop D4-selective radioligands for positron emission tomography (PET). The selected lead structures exhibit high D4R subtype selectivity and a suitable LogP values, rendering them attractive for the development of a D4-selective radioligand for PET-imaging. Two D4R-ligands, know from literature, were selected for labeling with fluorine-18 (t1/2=108 min), the most ideal positron emitting nuclide.D4R-radioligand [18F]I was synthesized from 2-[18F]fluorophenylpiperazine 2, obtained by an alcohol enhanced Cu(II)-mediated radiofluorination of the Boc-protected precursor 1 followed by deprotection of the radiolabeled intermediate with TFA. Subsequently, [18F]I was obtained by reductive amination with 3 in a total isolated radiochemical yield of 7 $\%$ within 2 h. Three independent auto radiographic studies with molar activities up to 90 GBq/µmol showed high content of non-specific binding that covers any possible specific binding. The chiral D4R-radioligand [18F]II was also obtained by alcohol enhanced Cu(II)-mediated radiofluorination of the boronic acid precursor 4 in a RCY of 66±5 $\%$ within 60 min after isolation by semi-preparative HPLC. Preliminary in vitro autoradiographic study indicates specific binding of [18F]II in areas with D4-expression, consistent with results published earlier.}, month = {Sep}, date = {2019-09-01}, organization = {DPhG Annual Meeting 2019, Heidelberg (Germany), 1 Sep 2019 - 3 Sep 2019}, subtyp = {After Call}, cin = {INM-5}, cid = {I:(DE-Juel1)INM-5-20090406}, pnm = {573 - Neuroimaging (POF3-573)}, pid = {G:(DE-HGF)POF3-573}, typ = {PUB:(DE-HGF)24}, url = {https://juser.fz-juelich.de/record/865229}, }