Dihydropyridines are the most extensively used drugs in the treatment of hypertension. Nifedipine is the prototype of calcium channel blocker. The dihydropyridine derivative compounds of diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (DHPB), diethyl 4-(furan-2yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (DHPF), and diethyl-4-phenyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (DHPP) were synthesized using the Hantzsch reaction. The DFT/B3LYP exchange–correlation function was employed to perform quantum chemical calculations such as molecular geometry optimization, vibrational analysis, frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural bond order (NBO), global reactive descriptors, and Fukui functions to determine the structural characteristics related to biological activity of the compounds. The molecular docking and molecular dynamics were employed to study the binding interaction and stability of protein–ligand complex in the docked site.