2-Amino-2,3-dihydro-1H-2λ5-[1,3,2]diazaphospholo[4,5-b]pyridin-2-one-based urea and thiourea derivatives: synthesis, molecular docking study and evaluation of anti-inflammatory and antimicrobial activities

A series of new class of P-heterocycle encompassing urea and thiourea derivatives, N -(substitutedphenyl)- N′ -(2-oxo-2,3-dihydro-1 H -2λ 5 -[1,3,2]diazaphospholo[4,5- b ]pyridin-2-yl)ureas 11a – e/ thioureas 11f – k , was accomplished from the precursor intermediate, 2-amino-2,3-dihydro-1 H -2λ 5 -[1,3,2]diazaphospholo[4,5- b ]pyridin-2-one, 9 . The compound 9 was obtained by cyclization of pyridine-2,3-diamine, 6 with POCl 3 followed by amidation with NaNH 2 . The products were tested for their in vitro and in vivo anti-inflammatory activity, and in vitro antimicrobial activity including minimum inhibitory concentration. Compounds 11a , 11d and 11j exhibited comparable anti-inflammatory activity to the standard drug, diclofenac, both in in vitro and in vivo assays, which might be due to the presence of lipophilic functional groups, F, NO 2 and CF 3 . The compounds 11c and 11j exhibited potential growth of inhibition against selected bacterial and fungal strains at lower minimum inhibitory concentrations, while most of the thiourea-linked analogues exhibited good antimicrobial activity. A molecular modelling study was performed on cyclooxygenase isoenzyme (COX-2) to investigate the hypothetical binding mode of the most active anti-inflammatory agents, and binding conformers were proposed.