Abstract
The novel group of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives was designed as potential anticonvulsants using GABA pharmacophore and corresponding heterocyclic moieties. A number of compounds of this group were synthesized and studied in the maximum electroshock seizure (MES) test and in the model of primary-generalized convulsions caused by subcutaneous pentylenetetrazole (scPTZ) in mice. The most active compound in the MES test was found to be 1a (N-(3-nitrocoumarin-4-yl)-4-aminobutyric acid) at a dose range of 60–80 mg/kg that increased the number of survived animals up to 60% in comparison with the control group, whose survival rate was 10%. Compounds 1d (N-(3,6-dinitrocoumarin-4-yl)-4-amino-butyric acid methyl ester) at doses of 10–40 mg/kg and 3a (N-(3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-4-amino-butyric acid methyl ester) at a dose of 12.5 mg/kg had the most pronounced anticonvulsant effect in scPTZ test.
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The work was carried out according to the state order of 2019–2021, topic No. 0521-2019-0008 in Zakusov Research Institute of Pharmacology “Design and synthesis of new heterocyclic compounds with potential pharmacological activity”.
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Mokrov, G.V., Litvinova, S.A., Voronina, T.A. et al. Design, synthesis, and anticonvulsant evaluation of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives. Med Chem Res 28, 1901–1911 (2019). https://doi.org/10.1007/s00044-019-02422-5
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DOI: https://doi.org/10.1007/s00044-019-02422-5