129841-10-7Relevant academic research and scientific papers
Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors
Kuegler, Fabian,Ermert, Johannes,Coenen, Heinz H.
, p. 609 - 618 (2013/12/04)
The D4 receptor is of high interest for research and clinical application but puts high demands on appropriate radioligands to be useful tools for investigation. Search for adequate radioligands suitable for in vivo imaging is therefore still in progress. The potential neuroleptic drug 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to the D4 receptor. Derivatization of this lead structure by adding hydrophilic moieties was carried out in order to lower its lipophilicity what led to three new putative dopamine receptor D4 ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct 18F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]- piperazin-1-yl)benzodioxin were successfully synthesized in 18F- labeled form with radiochemical yields of 9-35% and molar activities of 30-60 GBq/μmol using one-pot procedures. 2013 John Wiley & Sons, Ltd. Derivatives of the lead structure 6-(4-[4-fluorobenzyl]-piperazine-1-yl) benzodioxin were successfully synthesized, labeled via direct 18F-substitution or build-up synthesis leading to new putative radioligands for imaging of the dopamine D4 receptor. Reductive amination proved as the method of choice for preparation of substituted benzyl-derivatives of piperazine as precursors and standards, and also superior for build-up radiofluorination (RCY = 9 - 35;%) in comparison to direct 18F- labeling (RCY = 1 - 5;%).
Evaluation of 18F-labeled benzodioxine piperazine-based dopamine D4 receptor ligands: Lipophilicity as a determinate of nonspecific binding
Kügler, Fabian,Sihver, Wiebke,Ermert, Johannes,Hübner, Harald,Gmeiner, Peter,Prante, Olaf,Coenen, Heinz H.
experimental part, p. 8343 - 8352 (2012/02/04)
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 D4 ligands displaying high affinity (Ki = 1.1-15 nM) and D2/Dsub
Effect of aldehyde and methoxy substituents on nucleophilic aromatic substitution by [18F]fluoride
Shen, Bin,L?ffler, Dirk,Zeller, Klaus-Peter,übele, Michael,Reischl, Gerald,Machulla, Hans-Jürgen
, p. 1461 - 1468 (2008/09/18)
For a series of benzaldehydes only with a leaving group or with both a leaving group and a single methoxy substituent 18F-fluorination via nucleophilic aromatic substitution (SNAr) was studied in DMF and Me2SO. In general, the radiochemical yields were clearly higher in DMF than in Me2SO. In the fluorodehalogenation reaction (leaving group: halogen = Br, Cl), extremely low radiochemical yields were observed in Me2SO (2SO (within 3 min reaction time, 90% of the precursor was consumed; radiochemical yield = 1.0 ± 0.5%); however, in DMF oxidation was always kept at a low level during the entire reaction (13C-NMR ppm values of the aromatic carbon atom bearing the leaving group.
NO-CARRIER ADDED (NCA) ARYL FLUORIDES VIA THE NUCLEOPHILIC AROMATIC SUBSTITUTION OF ELECTRON-RICH AROMATIC RINGS
Ding, Y.-S.,Shiue, C.-Y.,Fowler, J. S.,Wolf, A. P.,Plenevaux, A.
, p. 189 - 205 (2007/10/02)
Nucleophilic aromatic substitution by fluoride ion has been demonstrated on rings containing electron donating groups in addition to the necessary electron withdrawing and leaving groups.The reaction of (18)F- with a series of aromatic nitro aldehydes having protected hydroxyl substituents on the ring was studied.The reactivity of the aromatic ring towards nucleophilic substitution to give (18)F-labeled aromatic fluoroaldehyde derivatives is correlated with electron density at the reaction center.The effect of a number of protected hydroxyl substituents is reported. 13C-NMR was used as a sensitive probe for the changes in electron distribution at the ring carbon atoms.Radiochemical yield correlated with ppm values at the reaction center.This methodology has been applied to the synthesis of no-carrier-added(NCA) 6-fluoro-L-DOPA.The extension of this strategy to the syntheses of other labeled pharmaceuticals appears promising.
