Published: 2017-06-23

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

Full Text:



Variankaval N, Cote AS, Doherty MF. From Form to Function: Crystallization of Active Pharmaceutical Ingredients. AIChE Journal. 2008;54(7):1682-88.

Bauer JF. Polymorphism: A Critical Consideration in Pharmaceutical Development, Manufacturing, and Stability. Journal of Validation Technology. 2008;14(4):15-23.

Gore SS, Jagdale SC, Kuchekar BS. Review on- Pharmaceutical product development Stages. International Journal of Pharma Sciences. 2014;4(5):707-12.

Severina AI, Georgiyants VА, Shtrygol SY, Kavraiskyi DP. Synthesis and alkylation of 1-aryl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-ones as possible anticonvulsant agents. Der Pharma Che. 2015; 7(11):43-8.

Severina AI, Kavraiskyi DP, Shtrygol’ SY, Georgiyants VА. Pat. 103378 UA, ICP А 61 К31/505. R1- 5-aryl-1,5-dihydro-4H-pyrazol [3,4-d] pyrimidine-4-ones that exhibit anticonvulsant activity / Publ. 10.12.2015, Bul. N 23.

Kavraiskyi DP, Shtrygol’ SY, Georgiyants VА, Severina AI. Scrining Screening investigation of novel pyrazolo[3,4-d]pyrimidine-4-one derivatives on anticonvulsant activity. Pharmacology and drug toxicity. 2016;3(49):16-28.

Kavraiskyi DP, Shtrygol’ SY, Georgiyants VА, Severina AI. Experimental study of new pyrazolo[3,4-D]pyrimidine-4-one derivatives for anticonvulsant activity spectrum. Sience Rise. 2016;1(1):10-7.

Korolyov DV, Suvorov KA. Determination of the disperse composition of powders by the microscopic method. Methodical instructions to laboratory work. Sain SPbGTI (TU), St. Petersburg, Russia: StPGTI (TU); 2002:24.

Golovenko MJ, Gromov L. Сlinical study specific activity of potential anticonvulsants: Method. recommendations. Kiev, Ukraine: Avicenna; 2003:26.

Mironova AN, Bunyatyan ND, Vasileva AN. Guidelines for conducting pre-clinical trials of medicines. Part one. Moscow, Russia: Grif and K; 2012:944.

Shtrygol SY. Pharmacological effects modulation at different salt conditions. Kharkiv, Ukraine: Avista-VLT; 2007:360.

Pharmacopoeia of Ukraine / Ukrainian scientific center pharmacopoeia quality medicines. 2nd Ed. Kharkiv, Ukraine; 2015:1:1128.

Setkina SB, Hishova ОМ. Biopharmaceutical aspects of drug technology and ways of modification of bioavailability. Biopharmaceutical aspects and bioavailability. 2014;4(13):162-72.