Azaadamantanes, a New Promising Scaffold for Medical Chemistry.

Azaadamantanes are nitrogen-containing analogs of adamantane, which contain one or more nitrogen atoms instead of carbon atoms. This substitution leads to several specific chemical and physical properties. The azaadamantane derivatives have less lipophilicity compared to their adamantane analogs, which affects both their interaction with biological targets and bioavailability. The significant increase in the number of publications during the last decade (2009-2020) concerning the study of reactivity and biological activity of azaadamantanes and their derivatives indicates a great theoretical and practical interest in these compounds. Compounds with pronounced biological activity have been already discovered among azaadamantane derivatives. The review is devoted to the biological activity of azaadamantanes and their derivatives. It presents the main methods for the synthesis of di- and triazaadamantanes and summarizes the accumulated data on studying the biological activity of these compounds. The prospects for the use of azaadamantanes in medical chemistry and pharmacology are discussed.

[Inhibitory Properties of Nitrogen-Containing Adamantane Derivatives with Monoterpenoid Fragments Against Tyrosyl-DNA Phosphodiesterase I].

It was found that compounds combining diazaadamantane and monoterpenoid fragments are potent inhibitors of new structural type of human recombinant DNA repair enzyme Tyrosyl-DNA phosphodiesterase I (Tdp1). It was demonstrated that the inhibition efficiency depended on the length and flexibility of the aliphatic chain of the substituent.

Effect of 2-aminoadamantane derivatives on behavior of mice in a modified light/dark test.

The effects of two derivatives of 2-aminoadamantane, enantiomers J447H and J579, on the behavior of male and female C57Bl/6J mice were studied using a modified light/dark test. The substances differed by their effects on the behavior of male mice. J579 reduced the number of rearings. J447H in a dose of 1 mg/kg affected more parameters: it reduced exploratory activity 1 h after administration and stimulated exploratory and motor activity in 2 h. In female mice, J447H significantly reduced the number of peepings into holes in 2 h after administration. The results indicate that further analysis of the effects of J579 and especially J447H is required.