Novel 6-bromo-imidazo[4,5-b]pyridine derivatives (2-4, 5a-13a, and 6b, 8b-13b) have been synthesized based on a developed systematic approach involving the condensation of 5-Bromo-2,3-diaminopyridine with a suitable aromatic aldehyde in the presence of molecular iodine in water, followed by alkylation reactions using different alkyl dibromide agents. The synthesized compounds were characterized by the NMR spectroscopy technique. The structures of 8a, 9a, 12a, and 11b were confirmed using monocrystalline X-ray crystallography. Theoretical calculations have been carried out using DFT and TD-DFT methods at the B3LYP/6-31G++(d,p) level of theory. Intermolecular contacts between units of 8a, 9a, 12a, and 11b were determined through the Hirshfeld surface analysis. The molecular docking study has been performed to determine the binding affinity of 8a, 9a, 12a, and 11b into the binding site of S. aureus tyrosyl-tRNA synthetase as a target enzyme, and the results revealed that 9a is the most potent compound among the selected compounds with a binding affinity of -8.74 Kcal/mol.Communicated by Ramaswamy H. Sarma.
Keywords: DFT; Hirshfeld surface; Imidazo[4,5-b]pyridine; alkylation; condensation; molecular docking.