A series of NO-donor diarylimidazoles derived from the lead compound Cimicoxib were synthesized andevaluated for their COX-2 inhibitory activity and their stability in whole blood as well as for vasodilatorproperties. The products are partly transformed into the corresponding alcohols following 24-h incubationin whole blood. All of them display good COX-1/COX-2 selectivity, but are less potent than the lead; amolecular modeling study was carried out to investigate their binding mode. The compounds are also capableof relaxing rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism; this propertycould confer reduced cardiotoxicity with respect to traditional COX-2 inhibitors.
