50372-80-0Relevant articles and documents
Synthesis, radiosynthesis and first in vitro evaluation of novel PET-tracers for the dopamine transporter: [11C]IPCIT and [ 18F]FE@IPCIT
Rami-Mark, Christina,Bornatowicz, Birgit,Fink, Cornel,Otter, Paul,Ungersboeck, Johanna,Vraka, Chrysoula,Haeusler, Daniela,Nics, Lukas,Spreitzer, Helmut,Hacker, Marcus,Mitterhauser, Markus,Wadsak, Wolfgang
supporting information, p. 7562 - 7569 (2014/01/06)
Introduction Present data indicate that merging beneficial structural elements from previously published DAT-ligands highest DAT affinity, selectivity and a suitable metabolic profile should be achieved. This combination led to the development of IPCIT and FE@IPCIT. Methods Precursor synthesis was done starting from cocaine in a six step reaction. O-[11C]-methylation was established using [11C]methyl iodide, optimized and subsequently automated. Small scale 18F-fluroroethylation as well as optimization of reaction parameters and automation were performed. Affinity and selectivity of the candidate substances were tested in standard binding experiments on human membranes. Metabolic stability and blood-brain-barrier (BBB) penetration were determined. Results Precursor compound, IPCITacid, and reference compounds, IPCIT and FE@IPCIT, were obtained in 4.9%, 12.7% and 4.1% yield, respectively. Automated radiosynthesis of [11C]IPCIT yielded 1.9 ± 0.7 GBq (12.5 ± 4%, corrected for decay). Optimum parameters for 18F-fluoroethylation were 110 C for 15 min under TBAH catalysis, yielding 67 ± 16% radiochemical incorporation. Affinity was determined as 1.7 ± 0.6 nM for IPCIT, 1.3 ± 0.2 nM for FE@IPCIT and 37 ± 13 nM for the precursor molecule, IPCIT-acid. Results from in vitro and in silico evaluations revealed high stability but also high lipophilicity. Conclusion Present data indicate high affinity and stability of both IPCIT and FE@IPCIT. Radiolabelling, optimization of reaction parameters and automation succeeded. On the other hand, data concerning BBB-penetration are not promising.
Fluoralkenyl nortropanes
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Page column 17, (2008/06/13)
Provided are compounds of the following formula: wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.
Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies
Chung, Kyoo-Hyun,Lim, Choong Hwan,Lee, Dong Reyoul,Jin, Changbae,Chi, Dae Yoon
, p. 3077 - 3080 (2007/10/03)
Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3β-aryl-2β-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.