Design, synthesis, and anticonvulsant evaluation of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives

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 electrosh...

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Bibliographic Details
Published in:Medicinal chemistry research 2019-11, Vol.28 (11), p.1901-1911
Main Authors: Mokrov, G. V., Litvinova, S. A., Voronina, T. A., Nerobkova, L. N., Kutepova, I. S., Kovalev, I. G., Gudasheva, T. A., Durnev, A. D.
Format: Article
Language:English
Subjects:
Anticonvulsants
Biochemistry
Biomedical and Life Sciences
Biomedicine
Butyric acid
Cell Biology
Convulsions
Derivatives
Original Research
Pentylenetetrazole
Pharmacology/Toxicology
Seizures
γ-Aminobutyric acid
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Summary: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.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-019-02422-5