The Effects of Nitroazolopyrimidines on the A1 Adenosine Receptor and Intraocular Pressure in Rats

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 A 1 adenosine receptor inhibitors and the role of this biological target in the modulation of intraocular pressure, an important factor in the pathogen...

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Published in:Russian journal of bioorganic chemistry 2022, Vol.48 (4), p.777-782
Main Authors: Savateev, K. V., Rusinov, V. L., Kotovskaya, S. K., Spasov, A. A., Naumenko, L. V., Taran, A. S., Brigadirova, A. A., Yakovlev, D. S., Sultanova, K. T., Shcherbakova, N. M.
Format: Article
Language:English
Subjects:
Adenosine
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Doxorubicin
Glaucoma
In vivo methods and tests
Intraocular pressure
Life Sciences
Organic Chemistry
Pathogenesis
Pyrimidines
Receptors
Structural analysis
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Summary: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 A 1 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 A 1 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.
ISSN:1068-1620
1608-330X
DOI:10.1134/S1068162022040185