New derivatives of 2-(N-arylmethylideneamine) benzophenone oxime as potential radiopharmaceuticals for brain imaging.
BACKGROUND
The aim of this work was the development of a sufficient method for synthesis and radiolabelling with technetium- 99m a new class of compounds as potential ligands for brain imaging.


METHODS
The synthesis of new ligands with the structure of 2-(N-arylmethylideneamine) benzophenone oxime (6-10) based on the cyclocondensation of appropriate 2-aminobenzophenone oxime 1-2 with respective aldehydes 3-4 or ketone 5 in acidic conditions. During our experiments in dependencies from the reaction conditions, compounds with the structure of Schiff's bases (6-10) or 3N-oxides 1,2-dihrydroquinazoline derivatives were obtained. Labelling of compounds 6 or 7 with technetium- 99m was done by stannous chloride reduction according to two methods (in ethyl alcohol or in chloroform) following the radiolabelling method of HM-PAO. The complex (99m)Tc-HM-PAO was the leading compound in our computational calculations with geometrical optimisation of a molecule. Using molecular modelling (semi-empirical method ZINDO) we have determined the electrostatic potential for the obtained ligands. Additionally we have calculated total energy,binding energy, heat of formation and several 3D-QSAR parameters for theoretically possible complexes of (99m)Tc with the obtained ligands.


RESULTS
As a result of our experiments a method of a synthesis of new compounds 6 and 7 has been developed. Computational calculations were performed using the HyperChem 4.5 program. These calculations confirmed our hypothesis that only ligand 7 is able to form a complex with (99m)Tc and this complex possesses lipophilic properties.


CONCLUSIONS
Complex (99m)Tc-7, due to its lipophilic properties, is a potential radiopharmaceutical for the brain imaging.
Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Łódź, Poland. eolasik@farm.pharm.am.lodz.pl
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E
Mikiciuk-Olasik
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E
Zurek
R
R
Mikołajczak
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E
Zakrzewska
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K
Błaszczak-Swiatkiewicz