N-Substituted phenyl/cyclohexyl-2-(pyridine-4-carbonyl) hydrazine-1-carbothioamides (2a–r) were synthesized, characterized by spectral and analytical data. The compounds were evaluated for antibacterial activity by the disc diffusion method. Most of the compounds showed activity against Gram-positive bacteria. Compound 2h with 4-Sulfapyrimidine phenyl substitution was found to be the most promising candidate, active against Gram-positive and methicillin-resistant