Wang-OSO3H catalyzed a greener approach for the synthesis of imidazo [1, 2-a] pyridin-3-amine derivatives as potential TNF-α inhibitors

15 12 2024

Authors: Jyothi Shivanoori, Mallesham Baldha, Sunder Kumar Kolli, Ravikumar Kapavarapu, Manojit Pal

The known anti-inflammatory activities of compounds containing the imidazo[1,2-a]pyridin-3-amine prompted us exploring the TNF-α inhibitory properties of a series of compounds based on this framework. These compounds were accessed via an eco-friendly approach that involved Wang-OSO3H catalyzed 3-component reaction of 2-aminopyridines, aldehydes and isocyanides in aqueous media under ultrasound irradiation. This sonochemical method furnished a range of desired imidazo[1,2-a]pyridin-3-amine derivatives in good to satisfactory yields. The intermediacy of an imine intermediate through which the reaction seemed to proceed has been demonstrated. In vitro evaluation of synthesized compounds against TNF-α led to the identification of compound 4a, 4b and 4d as initial hits with IC50 in the range ∼6.2–6.9 µM. This was further supported by the in silico docking studies that revealed TYR135, TYR227 …