I. S. Morozov, N. Klimova, L. N. Lavrova
2006
Citations
0
Influential Citations
7
Citations
Journal
Pharmaceutical Chemistry Journal
Abstract
The class of adamantane derivatives was reported to contain substances possessing psychotropic activity of the stimulator type [1, 2]. Their mechanism of action is based on influencing the central dopaminergic neuromediator systems [3]. The known drugs of this type (e.g., midantane and gludantan) are essentially the adamantane derivatives substituted at the cycle junction site, although these compounds are less active compared to derivatives substituted at the bridging position [4, 5]. The adamantane derivatives substituted at the bridging position, including arylaminoadamantanes, are insufficiently studied. The presence of an arylamino group in the structure can be expected to enhance the effect upon the central dopaminergic and noradrenergic neuromediator systems. It was demonstrated that N-(adamant-2-yl)aniline possessed a pronounced psychotropic activity, albeit at a high toxicity [6]. In order to search for the more promising compounds, we have synthesized a series of new N-(adamant-2-yl)aniline derivatives (Ia Is) and studied their neurotropic activity. Initial compounds in the synthesis were represented by adamantanone and the corresponding substituted anilines. Adamantanone was obtained by a method described previously [7], based on the adamantane oxidation with sulfuric acid and the product isolation by vapor distillation. The target compounds Ia Is were synthesized using the Leuckart reaction, by boiling adamantanone with the corre-" sponding anilines in a formic acid medium. The resulting forrnyl derivatives of the amines were subjected to acid hydrolysis. The technical-purity hydrochlorides were separated by filtration and suspended in an aqueous sodium hydroxide to obtain compounds I a Is in the form of bases upon crystallization from ethanol. The final hydrochto-