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Volume: 9, Issue: 2, February, 2019
DOI: 10.7324/JAPS.2019.90202



Research Article

Synthesis and anticonvulsant activity of 6-methyl-2-thioxo-2, 3-dihydropyrimidin-4(1H)-one acetamides

Hanna Severina1, Olha Skupa2, Andrei Khairulin3, Natalya Voloshchuk2, Victoria Georgiyants1

  Author Affiliations


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 the reaction 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 with corresponding 2-chloroacetamides in Dimethylformamide (DMF) in the presence of potassium carbonate. The structure of compounds was confirmed by 1 H Nuclear magnetic resonance (NMR)-spectroscopy, LCMS, and elemental analysis. A screening of anticonvulsant activity of synthesized compounds was carried out using the pentylenetetrazole- and maximal electroshock-induced seizures models. In these studies, the highest anticonvulsant activity demonstrated a compound 5.5 2-[(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio]-N-(4-bromophenyl)-acetamide, which decreased the lethality, the number and the severity of seizures, and increased their latent period. For these compound parameters of ЕD50, 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.

Keywords:

2-thiopyrimidine, alkylation, acetamides, anticonvulsant activity.



Citation: Severina H, Skupa O, Khairulin A, Voloshchuk N, Georgiyants V. Synthesis and anticonvulsant activity of 6-methyl-2- thioxo-2,3-dihydropyrimidin-4(1H)-one acetamides. J Appl Pharm Sci, 2019; 9(02):012–019.


Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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