Perekhoda L. Molecular modeling and purposeful synthesis of anticonvulsants among derivatives of five-membered di(three)azaheterocycles

The thesis is devoted to the development of the methodology for rational design of new biologically active substances as potential anticonvulsants among the derivatives of five-membered di(three)azaheterocyсls. The developed algorithm of the integrated approach to molecular design of biologically active substances includes the LSР, PASS prediction, molecular docking, synthesis perspective substans, on the basis of the planned pharmacological properties, pharmacological screening for anticonvulsant activity, SAR and QSAR-analysis. The correctness of the algorithm proposed has been proved experimentally – by synthesis about 300 derivatives of 1-R-5-methyl(amino)-4-R-sulfonyl-1,2,3-triazoles(1H), anilides of 1-R-5-methyl(ami¬no)-1,2,3-triazole(1Н)-4-сarboxylic acid, 1-R-1,2,3-triazole(1Н)-4,5-diсarboxylic acids and their methyl esters, derivatives of 1,2,4-triazolo(1,5–а]pyrimidines, amides of 5-R-1,3,4-oxa(thia)diazol-2-ylthioacetic acid, 5-R-2-mercapto-1,3,4-oxadiazol-2-ylthio-1-phenones and by the pharmacological screening of substances synthesised for anticonvulsant activity. For this group of compounds we examined molecular docking to anticonvulsants target to optimize further screening; SAR, 2D and 3D QSAR analysis for the first time. The leader substance 3-chloro-4-methoxyanilide of 1-(3'-fluorophenyl)-5-methyl-1,2,3-triazole(1H)-4-carboxylic acid – epifin have been chosen. For this substance MCQ has been draft.