Design, Synthesis and In-Silico Evaluation Of 2-Alkyl/Aryl,5- Substituted Aryl 1,3,4-Oxadiazole Derivatives as Potential Anti-Alzheimer Agents

Alzheimer’s disease (AD), a neurodegenerative disorder marked by cognitive decline, remains a significant therapeutic challenge. This study aimed to design, synthesize, and evaluate novel 1,3,4-oxadiazole derivatives as potential nootropic agents inspired by the activity profile of Piracetam. A library of 30 compounds (PS-1 to PS-30) was designed and screened using in-silico tools including PASS Online, Swiss ADME, ProTox-III, and molecular docking (Molsoft.icm-pro.v3.8.3). Ten compounds were synthesized based on predicted nootropic activity, blood-brain barrier (BBB) permeability, bioavailability, and low toxicity. Docking scores for these compounds ranged from –21 to –25 kcal/mol, outperforming Piracetam (–21 kcal/mol), while SwissADME and ProTox-III confirmed favorable ADME and safety profiles. These findings highlight the therapeutic potential of 1,3,4-oxadiazole derivatives as nootropic agents and support their further development in the treatment of AD and related cognitive disorders.