The present study reports a convenient approach for the synthesis of cyanoacetamide based derivatives (7-27) via two-step process involving Knoevenagel reaction, followed by three component reaction to avail desired compounds. All the synthesized compounds were obtained in good to excellent yield and extensively characterized employing 1 H NMR, 13 C NMR, mass spectrometry and physical parameters. Further, these compounds were screened for urease inhibition. All of the synthesized compounds exhibited good to excellent urease activity notably compound 15 and 19 showed excellent urease inhibition activity with IC50 valuẽ 17.34 μg/mL and 36.75 μg/mL in comparison to thiourea (used as standard) having IC50 value ~27.5 μg/mL.