50370-54-2Relevant 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.
Synthesis, ligand binding, QSAR, and CoMFA study of 3β-(p-substituted phenyl)tropane-2β-carboxylic acid methyl esters
Carroll,Gao,Rahman,Abraham,Parham,Lewin,Boja,Kuhar
, p. 2719 - 2725 (2007/10/02)
A series of 3β-(p-substituted phenyl)tropane-2β-carboxylic acid methyl esters (2) were synthesized and found to possess high affinity for the cocaine binding site in rat striatum. The p-chloro (2c) and p-iodo (2n) compounds, which were the most potent analogues prepared, were found to be 85 and 78 times more potent than (-)-cocaine. The p-bromo (2m) and p-methyl (2d) were also 56 and 60 times more potent than cocaine. QSAR and CoMFA studies were conducted to correlate binding affinity of the cocaine analogues with their structural features. Whereas the QSAR study gave relatively low correlations, the CoMFA study gave a correlation with high predictive value.
