N-Substituted 4-sulfamoylbenzoic acid derivatives as inhibitors of cytosolic phospholipase A2α

Abstract

AbstractThe N,N-disubstituted 4-sulfamoylbenzoic acid derivative 3, which was found to be an inhibitor of cytosolic phospholipase A2α (cPLA2α) with micromolar activity in a ligand-based virtual screening approach, was structurally modified to increase its enzyme inhibitory potency. Replacing the substituents on the sulfonamide nitrogen with other residues such as naphthyl, naphthylmethyl, indolylalkyl and differently substituted phenyl moieties did not lead to a significant increase in activity. Only strong structural convergence to the potent known benzhydrylindole-substituted benzoic acid derivatives that had served as templates in the virtual screening resulted in compounds with considerable potency. Thus, the sulfamoyl benzoic acid derivatives 85 and 88 showed submicromolar IC50 values against cPLA2α.