Spectroscopic, <scp>DFT</scp>, In Silico, and Estimation of Biological Activity of 2,4‐Dichloro‐6,7‐Dimethoxyquinazoline as a Potential Anti‐Alzheimer's Disease Therapeutic Agent

ABSTRACT Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive and behavioral decline. In this study, 2,4‐dichloro‐6,7‐dimethoxyquinazoline (DCDQ) was extensively analyzed using a combination of spectroscopic and computational approaches. Geometric parameters and vibrational modes were computed using DFT/B3LYP/6‐311++G(d,p), and experimental FT‐IR, FT‐Raman, and UV–vis spectrum confirmed the compound's structural properties. Time‐dependent DFT (TD‐DFT) calculations provided insights into the electronic structure, including HOMO‐LUMO energies and global reactivity descriptors. Molecular electrostatic potential (MEP) analysis and Mulliken population studies identified reactive sites and bonding characteristics, while NBO analysis revealed significant hyperconjugative interactions contributing to stability. Advanced topological analyses (ELF, LOL, NCI, and RDG) and QTAIM studies were performed using Multiwfn software to explore the compound's electron density distribution. Biological relevance was established through molecular docking studies, which highlighted a strong binding affinity of DCDQ with the 4EY7 protein (binding energy: −8.2 kcal/mol), suggesting its potential as a potent acetylcholinesterase (AChE) inhibitor. Molecular dynamics simulations further validated the stability of the protein‐ligand interaction. ADMET predictions also supported favorable pharmacokinetic and safety profiles of DCDQ. These findings collectively demonstrate the potential of DCDQ as a promising lead compound for the treatment of Alzheimer's disease, offering a solid foundation for future therapeutic development.