Hydrazones were considered as significant substrates in drug discovery process. Therefore, a series of some new 1-(4-(1-(2-(4-substitutedphenyl)hydrazono)ethyl)phenyl)-3-(4-nitrophenyl)urea derivatives (2-8) were synthesized as potential urease inhibitory agents. The synthesized compounds were characterized by FTIR, 1H NMR,13C NMR, and elemental analysis (C, H, N). All compounds were evaluated in vitro for urease inhibitory potential. Among synthesized compounds, 8, 7, 6, and 4 showed excellent activities (IC50) i.e. 10.13±0.40, 12.15±0.22, 17.81±0.36, and 22.95±0.47 μM, respectively. This study has culminated in the identification of some compounds which can serve as leads for new potent urease inhibitors