Derivatives of quinazolinone, piperazine, and amide have numerous significant medicinal applications, particularly in the pharmaceutical sector. As a result, the current in silico investigation attempted to use computational methods to determine the molecular properties, bioactivity score, and toxicity of various N-(4-oxo-2-(4-(4-(2-(substituted phenylamino) acetyl) piperazin-1-yl) phenyl) quinazolin-3(4H)-yl) benzamide derivatives. The investigation revealed that, except for molecular weight, the majority of the substances fitted Lipinski's rule of five, indicating drug-like properties. The bioactivity data revealed that the N-(4-oxo-2-(4-(4-(2-(substituted phenylamino) acetyl) piperazin-1-yl) phenyl) quinazolin-3(4H)-yl) benzamide derivatives were moderate active as GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor ligand, Protease inhibitor, and Enzyme inhibitor.None of the synthesized compounds were assessed to be cytotoxic and hepatotoxic based on the results of ProtTox-II.The evidence presented by the current study regarding the pharmacokinetic features and toxicity of recently synthesized derivatives& existing medications can be used to design and develop novel compounds that are more potent, more selective, and less toxic.