Three series of new cyclic sulfones have been prepared by a one-pot multi-component reaction (MCR) starting from the readily available dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide. The in silico screening of the synthesized compounds revealed their high anti-inflammatory, antiarthritic, antiasthmatic and antiallergic potential coupled with the strong probability levels of cystinyl aminopeptidase inhibition. The key structures were confirmed by 2D NMR techniques.