Synthesis of pyrazolo[1,5-a][1,3,5]triazine and oxazolo[4,5-d]pyrimidine derivatives and study of their vasodilator activity

Abstract

A number of pyrazolo[1,5-a][1,3,5]triazine and oxazolo[4,5-d]pyrimidine derivatives were synthesized and characterized. Pyrazolo[1,5-a][1,3,5]triazines with various substituents in the fourth position and a dichloromethyl group in the second position were obtained by the heterocyclization reaction of available N-(2,2-dichloro-1-cyanoethenyl)carboxamides and 5-aminopyrazoles. Oxazolo[4,5-d]pyrimidines were obtained by treating 2-phenyl-4-dichloromethylene-1,3-oxazol-5(4H)-one with the corresponding arylamidine hydrochloride in the presence of triethylamine. The resulting 4,5-dihydro-1H-imidazol-5(4)-ones undergo recyclization with subsequent cyclocondensation to the corresponding oxazolo[4,5-d]pyrimidin-7-ones when heated in pyridine. Oxazolo[4,5-d]pyrimidines with a labile chlorine atom in position 7, whose substitution with various amines leads to 7-aminoderivatives of oxazolo[4,5-d]pyrimidine, were obtained by heating the latter in phosphorus (V) oxychloride in the presence of N,N-dimethylaniline. The study of the effect of the synthesized compounds on vascular tone showed that some of the studied samples exhibited vasodilator activity of varying strength. It was established that 2-dichloromethyl-7-methyl-4-(furan-2-yl)pyrazolo[1,5-a][1,3,5]triazine and 2-dichloromethyl-7-methyl-4-(pyridin-3-yl)pyrazolo[1,5-a][1,3,5]triazine showed a pronounced dose-dependent vasodilator effect and therefore, subject to their further research, may be promising for the development of new vasodilator drugs. The study of the biological activity of oxazolo[4,5-d]pyrimidine derivatives did not reveal potential vasodilator agents among the presented compounds, as they demonstrated a low vasodilator effect or did not show vasoactivity.