Synthesis and anticonvulsant activity evaluation of n-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1h-quinazolin-3-yl)acetamide novel 1-benzylsubstituted derivatives

The aim. Synthesis of 1-benzylsubstituted derivatives N-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1h-quinazolin-3-yl)acetamide, and determination affinity to GABAergic biotargets with the following anticonvulsant activity estimation using PTZ-induced seizures model in mice.
 Materials methods. Standard organic synthesis methods were used; structure synthesized compounds was proved by elemental analysis, 1H 13C NMR spectroscopy, LC/MS method; composition – their individuality TLC AutoDockTools-1.5.6, as well AutoDock Vina software, used perform molecular docking. Anticonvulsant studied pentylenetetrazole-induced Results. A targeted N-[(2,4-dichlorophenyl)methyl]-2-(1-(R-benzyl)-2,4-dioxo-quinazolin-3-yl)acetamides obtained alkylation N-[(2,4-dichlorophenyl)methyl]-2-(2,4-dioxo-1H-quinazolin-3-yl)acetamide corresponding 1-chloromethylbenzene dimethylformamide environment excess potassium carbonate at a temperature 70-80 ˚С. Prediction 1-benzyl an vivo experiment carried out according results docking studies calculation for GABA receptor enzyme active sites, analysis conformational placement them. In relation binding energy, ligands inferior reference drugs: positive allosteric modulators benzamidine diazepam, inhibitor vigabatrin. substances did not show activity: only 2 have shown tendency manifestation criterion integral protective indicator reduction mortality 17 % compared control, prolonging time death animals. Comparison preliminary promising N-[(2,4-dichlorophenyl)methyl] -2-(2,4-dioxo-1H-quinazolin-3-yl) acetamide made possible prove pharmacophore role cyclic amide fragment manifestation.
 Conclusion. N-[(2,4-dichlorophenyl)methyl]-2-(1-(R-benzyl)-2,4-dioxo-quinazolin-3-yl)acetamides, which still described literature, out, mentioned proved. Unfortunately, on seizures. However, allowed establishing key NHCO activity. correlation between silico calculations found into sites PAMs GABAА GABAАТ, allows recommend given methodology tool streamline optimize screening