146725-33-9Relevant articles and documents
Synthesis of novel halo and tosyloxy nortropane derivatives as efficient precursors for the one-step synthesis of the dopamine transporter PET ligand [18F]FECNT
Pijarowska-Kruszyna,Jaron,Kachniarz,Kasprzak,Kowalska,Malkowski,Demphel,Dolle,Mikolajczak
, p. 148 - 157 (2014/04/03)
The fluorine-18 labeled nortropane derivative 2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) is a dopamine transporter (DAT) ligand. Currently, it is considered as reference for positron emission tomography imaging. Herein, the synthesis of novel precursors (N-tosyloxy-, chloro-, and bromo- analogues) for one-step radiosynthesis of [ 18F]FECNT is reported. Using the N-mesyloxy- precursor in a one-step radiosynthesis, the crude [18F]FECNT was obtained with the radiolabeling yield of 45 ± 10%, confirming the practical efficiency of this approach in the design of novel precursors for labeling. Copyright
Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes
Riss, Patrick Johannes,Hummerich, Rene,Schloss, Patrick
experimental part, p. 2688 - 2698 (2009/09/07)
A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.
Novel tropane-based irreversible ligands for the dopamine transporter
Zou,Kopajtic,Katz,Wirtz,Justice Jr.,Newman
, p. 4453 - 4461 (2007/10/03)
3α-(Diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4′-azido-3′-iodophenyl)butyl]- 3α-[bis(4′-fluorophenyl)methoxy]tropane, [125I]1, that covalently attached to the 1-2 transmembrane spanning region of the dopamine transporter (DAT). This was in contrast to the 4-7 transmembrane spanning region labeled by a cocaine-based photoaffinity label, [125I] 2 (RTI 82). To characterize further these different binding domains, photoaffinity ligands that had the 4′-azido-3′-iodophenyl substituent extended from the same position on the tropane ring were desirable. Thus, identification of the optimal alkyl linker between this substituent and the tropane nitrogen in the benztropine series was investigated to ultimately prepare the identical N-substituted analogue of 2. In this pursuit, the N-[4-(4′-azido-3′-iodophenyl)propyl] analogue of 3α-[bis(4′-fluorophenyl)methoxy]tropane (9a) was synthesized as well as two isothiocyanate analogues that do not require photoactivation (10a,b) for irreversible binding. The synthesis of these target compounds was achieved using a modification of the strategy developed for 1. Evaluation of these compounds for displacing [3H]WIN 35 428 binding at DAT in rat caudate putamen revealed that the 4′-azido-3′-iodophenylbutyl substituent, found in 1, provided optimal binding affinity and was chosen to replace the N-CH3 group on 2. Both the 4′-azido-3′-iodophenyl- and the 4′-isothiocyanatophenylbutyl analogues of 2 (25 and 26, respectively) were synthesized. Both products bound to DAT with comparable potency (IC50 = 30 nM) to RTI 82 (2). In addition, compound 26 demonstrated wash-resistant displacement of [3H]WIN 35 428 in HEK 293 cells stably transfected with hDAT. These ligands will provide important tools for further characterizing the binding domains for tropane-based dopamine uptake inhibitors at the DAT.
