NEW NO-DONORS WITH ANTITHROMBOTIC AND VASODILATING ACTIVITIES .16. 3-AMINO-1,2,4-OXADIAZOL-5-ONES AS PRODRUGS FOR HYDROXYGUANIDINES

Nineteen 4-substituted 1,2,4-oxadiazol-5-ones (6a-s) were prepared as prodrugs for lipophilic hydroxyguanidines which should be metabolized in vivo to nitric oxide. This hypothesis was rested indirectly by meas uring the antithrombotic properties of these compounds 2 h after oral administration to rats (60 mg/kg). In mesenteric arterioles seven comp ounds moderately (greater than or equal to 10%) inhibited the formatio n of thrombi by a laser beam. Maximum effects were observed in 6c (4-p entyl) and 6f (4-benzyl). The lack of activity in the corresponding 2- pentyloxadiazolone 10c, where no formation of nitric oxide seems possi ble, indirectly suggests that the antithrombotic properties of the tit le compounds could be mediated by the in vivo formation of nitric oxid e.