The Furoxan System: Design of Selective Nitric Oxide (NO) Donor Inhibitors of COX-2 Endowed with Anti-Aggregatory and Vasodilating Activities

Several NO donor 3,4-diphenylfuroxan (=3,4-diphenyl-1,2,5-oxadiazole 2-oxide) derivatives were synthesized and tested for their COX-inhibiting activities. The products were found to be selective COX-2 inhibitors, similar to the structurally related furazans (3,4-diphenyl-1,2,5-oxadiazole), devoid of the NO release property. This behavior was confirmed by a molecular-docking study. The NO-dependent platelet antiaggregatory and vasodilating activities of the new furoxans 5 - 7 were studied in vitro. These properties can be modulated by inserting an appropriate spacer between the 4-phenyl group and the furoxan ring, giving rise to new, selective COX-2 furoxan derivatives endowed with anti-aggregatory and vasodilating activities, and with potentially reduced cardiotoxicities.