The present study is devoted to functionalization of ethyl 2-{[3-cyano-6-(4-cyanophenyl)-4-(2,4- dichlorophenyl)pyridin-2-yl]oxy}acetate (1) by triazole-, oxadiazole- and pyrazole-nicotinonitrile hybrids, and study of their DFT and antimicrobial properties. Nicotinonitrile can be alkylated by ethyl bromoacetate, its following hydrazonolysis with hydrazine hydrate leads to the corresponding acetic acid derivative. The latter compound has been functionalized to 1,3,4-oxadiazoles by the reaction with carboxylic acid derivatives in presence of phosphorus oxychloride. 1,2,4-Triazoles and pyrazoles have been obtained by heterocyclization of pyridine 1 with phenyl/ cyclohexyl isothiocyanate, acetyl acetone, ethyl acetoacetate, and ethyl cycanoacetate. Several products demonstrate moderate activity against some bacteria and fungi.