ИСТИНА

Pyrimidine derivatives are of high importance in living organisms and reveal a wide spectrum of biological activity. Recently novel reaction of three-component heterocyclization of gem-dihalocyclopropanes, nitrating or nitrosating agents and nitriles resulting in previously unknown 4-halogenopyrimidine N-oxides was discovered in our laboratory. In this work the synthetic approach to novel tetrahydroquinazoline derivatives based on this reaction was developed and a large series of heterocycles was obtained for studying their antiviral activity and activity towards AMPA receptor. Pyrimidine N-oxides I were obtained via the reaction of aromatic nucleophilic substitution. The synthetic approach to bis(pyrimidines) III included double SNAr reaction of 4-fluoropyrimidine N-oxides with different diamines and subsequent reduction of N-oxide fragment. Biological activity of pyrimidine N-oxides containing o-, m- or p-aminophenol and diamine moieties in C4 position and substituents of different size in C2 position (I,II) was investigated and the majority of compounds were found to possess antiviral activity in micromolar concentration. Also, bis(pyrimidines) with different diamine linkers (III) were found to act as AMPA-receptor negative modulators.