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The possibility of generating a carbanion using the reaction of 3-bromo-5,7-dimethylpyrazolo[1,5-a]pyrimidine with BunLi followed by the electrophilic addition was investigated. The obtained results provide evidence for the presence of several reaction centers in the substrate, resulting in the formation of unexpected reaction products. These results offer new prospects for the functionalization of pyrazolo[1,5-a]pyrimidines and allow the preparation of new pharmacologically active derivatives of this series. The structures and purity of all the synthesized compounds were confirmed by 1H and 13C NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray crystallography. [ABSTRACT FROM AUTHOR]

Various approaches to the synthesis of 3-halopyrazolo[1,5-a]pyrimidines were studied. It is shown that the most effective strategy consists in the construction of the azoloazine core followed by halogenation with N-iodo- or N-bromosuccinimide. A series of 3-halopyrazolo[1,5-a]pyrimidines, which are bioisosteric analogs of natural purine nucleic bases and the drug Triazavirin®, were synthesized using this strategy. The obtained compounds are interesting as precursors of novel C-nucleosides, which can be synthesized by C-C-coupling with (pseudo)ribosides containing a keto group. [ABSTRACT FROM AUTHOR]

Six compounds of the 5(7)-alkylamino-6-nitroazolopyrimidine and 8-alkylazolo[5,1-b]purine series were selected based on the structural analysis of A1 adenosine receptor inhibitors and the role of this biological target in the modulation of intraocular pressure, an important factor in the pathogenesis of glaucoma. These heterocycles were shown to exhibit a weak affinity towards the A1 adenosine receptor on an in vitro model of the adenosine-dependent change of the chronotropic effect on isolated atria of white mice. On the other hand, thiadiazolo[3,2-a]pyrimidines and triazolo[5,1-b]purine displayed an in vivo hypotensive effect in rats. The leading compound, 5-methyl-8-(hydroxyethyl)triazolo[5,1-b]purine) (0.2% solution), caused a 34% reduction of ophthalmotonus in 3 h without an adverse resorptive effect. In addition, using the MTT-test it was shown on the human HepG2 cell line that the heterocycles affecting the intraocular pressure were by one to two orders of magnitude less cytotoxic than the reference doxorubicin. [ABSTRACT FROM AUTHOR]