Synthesis of new sulfonamides as lipoxygenase inhibitors

The present study describes a convenient method for the synthesis of new lipoxygenase inhibitors, 4-(toluene- 4-sulfonylamino)-benzoic acids from p-amino benzoic acid. Reaction of p-amino benzoic acid with p-toluenesulfonyl chloride provided thirteen N- and O-alkylation products 4a-4m in moderate to good yields. Lipoxygenase inhibition of newly formed sulfonamide derivatives was investigated and some of these compounds 4m, 4g, 4e, 4f and 4j showed good lipoxygenase inhibitory activities with IC50 values ranged between 15.8 +/- 0.57 and 91.7 +/- 0.61 mu mol whilst all other compounds exhibited mild anti-lipoxygenase activities with IC50 values ranged between 139.2 +/- 0.75 and 232.1 +/- 0.78 mu mol. N-alkylated products were more active against the enzyme than O-alkylated or both N- and O-alkylated ones. All synthesized sulfonamides were recrystallized in chloroform to give these title compounds which were characterized using FTIR, H-1 NMR, C-13 NMR, elemental analysis and single crystal X-ray diffraction techniques. (C) 2012 Elsevier Ltd. All rights reserved.