Docking simulations, synthesis, and anti-inflammatory activity evaluation of 2-(N-alkyl)amino-3-nitroimidazo[1,2-a]pyridines

A set of imidazo[1,2-a]pyridine derivatives was submitted to a docking analysis on COX-1 and COX-2. Although most of the compounds showed affinity for both COX-1 and COX-2, compound 1h showed a higher COX-1 affinity while 1i was more selective to COX-2. None of them had ΔG value higher than indomethacin. Compounds 1b, 1c, and 1g were synthesized and evaluated as potential anti-inflammatory agents. Compound 2-(N-cyclopropyl) amino-3-nitroimidazo[1,2-a]pyridine (1c) which gave a very poor affinity for either COX-1 or COX-2, showed anti-inflammatory activity (20 mg/kg) on the cotton pellet granuloma bioassay, with no induction of gastrointestinal damage.