Synthesis and anticonvulsant activity of 6-methyl-2-thioxo-2, 3-dihydropyrimidin-4(1H)-one acetamides
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Date
2019-02
Journal Title
Journal ISSN
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Publisher
Open Science Publishers LLP
Abstract
This research aimed at synthesizing new potential anticonvulsants in the series of 2-(4-methyl-6-oxo-1,6-dihydropyrimidin2-yl)thio-acetamides. An initial intermediate 6-methyl-2-thioxo-2,3-dihydro-pyrimidin-4(1Н)-one was obtained by thereaction of thiourea with an acetoacetic ester in the presence of sodium methoxide. The target 2-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl) thioacetamides were synthesized by alkylation of initial 6-methyl-2-thiopyrimidin-4-one withcorresponding 2-chloroacetamides in Dimethylformamide (DMF) in the presence of potassium carbonate. The structureof compounds was confirmed by 1H Nuclear magnetic resonance (NMR)-spectroscopy, LCMS, and elemental analysis.A screening of anticonvulsant activity of synthesized compounds was carried out using the pentylenetetrazole- andmaximal electroshock-induced seizures models. In these studies, the highest anticonvulsant activity demonstrated acompound 5.5 2-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio]-N-(4-bromophenyl)-acetamide, which decreased thelethality, the number and the severity of seizures, and increased their latent period. For these compound parameters ofЕD50, acute (LD50) and neurotoxicity (TD50), as well as therapeutic (TI) and protective (PI) indexes were determined.Logical structure analysis of anticonvulsant activity screening revealed some patterns of “structure–activity” relationship.
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Keywords
2-thiopyrimidine, alkylation, acetamides, anticonvulsant activity
Citation
Severina Hanna, Olha Skupa, Khairulin Andrei, Voloshchuk Natalya, Georgiyants Victoria. Synthesis and anticonvulsant activity of 6-methyl-2-thioxo-2, 3-dihydropyrimidin-4(1H)-one acetamides. Journal of Applied Pharmaceutical Science. 2019 Feb; 2019 Feb: 012-019