Design and studies of newer Hydrazine-carboxamides is reported here. Hydrazine-carboxamides has shown a promising anticancer activity. A series of novel 2-(Substituted Benzylidene/Ethylidene)-N-(Substituted-Phenyl) Hydrazine Carboxamides derivatives were synthesised and were identified by TCL method using suitable solvent system, also they are confirmed by determination of their melting point further their structure were confirmed by Spectral analysis. Novel series of Hydrazine-carboxamides is synthesised using water-ethanol (2:1) solvent system. New Hydrazine-carboxamides analogues were designed using the scaffold hoping technique. All the Hydrazine-carboxamides analogues were studied for their ADME profiles and toxicity studies. All the compounds were found to follow the Lipinski’s rule of 5 with safe toxicity profile (Class IV compound) against immunotoxicity, mutagenicity and toxicity. All of the compounds were designed, followed by their molecular docking against EGFR Kinase Domain T790m/L858r (PDB code: 3W2R). One of the appealing cancer targets demonstrated an efficient binding within the binding site of EGFR Kinase. Analogue 4a with docking score = −7.51 kcal/mol shown good binding with the site & can be further explore and evaluate for significant anticancer activity.