Dependence of anticonvulsant activity of 1-aryl-1, 5-dihydro-4H-pyrazole (3,4-d) pyrimidine-4-one derivatives on biopharmaceutical factors

Anna I. Severina, Dmitryi P. Kavraiskyi, Inna V. Kovalevska, Sergey Yu. Shtrygol’, Elena A. Ruban, Victoria A. Georgiyants


Background: We have synthesized three 5-R-1-aryl-1,5-dihydro-4Н-pyrazole(3,4-d)pyrimidine-4-one derivatives that previously have demonstrated powerful anticonvulsant activity. A great number of physicochemical factors are known to influence on bioavailability and stability of active pharmaceutical ingredients. Therefore the purpose of research was to determine the effect of purification technology and dispersibility of 5-R-1-aryl-1, 5-dihydro-4Н-pyrazole (3,4-d) pyrimidine-4-one derivatives on their anticonvulsant activity.

Methods: The anticonvulsant effect of this compounds was studied in a model of pentylenetetrazole-induced seizure in mice.

Results: The results obtained revealed the optimal solvent for recrystallization of compounds to be isopropanol: compounds, purified by recrystallization from isopropanol, had higher solubility in water and tween; also, they had a tendency to increase anticonvulsant activity. It was found that there is a significant dependence of the latter on compound’s dispersion - the smaller the size of crystals the higher anticonvulsant activity.

Conclusions: The dependence of anticonvulsant activity of compounds on the degree of dispersion was proved: the smaller particle size the higher anticonvulsant activity. This can be explained by fast dissolution of fine-dispersed substances, thus increasing the bioavailability if the compounds studied.


Anticonvulsants, Bioavailability, Pyrazole(3,4-d)pyrimidine-4-one derivatives

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