The chlorine atom of 2-chloronicotinonitrile derivative 2 has been substituted via its heating with ethyl 4-aminobenzoate to give the conforming ethyl 4-(3-cyano-pyridin-2-ylamino)benzoate scaffold 3, which underwent refluxing with hydrazine hydrate to produce the hydrazide derivative 4. The reaction of hydrazide 4 with ethyl acetoacetate furnished the corresponding 2-((4-(3-methyl-5-oxo-1H-pyrazole-1-carbonyl)phenyl)-amino)nicotinonitrile derivative 6 which reacted with phenyl isothiocyanate and chloroacetone, phenacyl chloride or ethyl bromoacetate to give the corresponding 2-((4-(4-(3-phenylthiazolylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl)-phenyl)amino)-4,6-dimethyl-nicotinonitriles 10a, 10b and 11. In general, all synthesized pyridine scaffolds revealed better activity against the Gram-positive bacterium (B. subtilis) rather than the Gram-negative bacterium (E. coli).