Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen

A novel set of compounds containing a unique '1-(nitrooxy)ethyl ester' group act as true prodrugs of aspirin and exhibit excellent oral bioavailability, NO-release profile and gastric-sparing properties. The same properties are also shown by the corresponding NO-naproxen prodrugs. Additionally, NO-aspirin prodrug exhibits antithrombotic activity comparable to that of aspirin. Dn = D1, D2, D3 and so on; D1C(O)OH = aspirin; D2C(O)OH = naproxen; R = methyl, ethyl, n-propyl or n-butyl; SGF = simulated gastric fluid; SIF = simulated intestinal fluid, HP = human plasma.41