NEW NO-DONORS WITH ANTITHROMBOTIC AND VASODILATING ACTIVITIES .12. MESOIONIC OXATRIAZOLES AND RELATED NONCYCLIC NITROSOHYDRAZINE DERIVATIVES

Mesoionic 1,2,3,4-oxatriazolimines and the corresponding oxatriazolone s were prepared and tested for their antiplatelet and antithrombotic a ctivities. In the Born-test 5-amino-3-phenyl-1,2,3,4-oxatriazolimine c hloride inhibited the platelet aggregation halfmaximally in a concentr ation of 50 nmol/L. Its N-ethoxycarbonyl derivative inhibited thrombus formation in arterioles of rats by 48% (10 mg/kg, 2 h after p.o. admi nistration). These effects appear to be related to the formation of in termediate nitrosohydrazine derivatives. This aspect was supported by the activities in noncyclic nitrosohydrazines (2 compds,), nitrosohydr azones (2) and nitrosohydra zides (11). Five of them exhibited an IC50 < 100 nmol/L in the Born-test. In a thrombotic model strong inhibitio n of thrombus formation was observed after intravenous application. Th e 1-nitroso-1-benzylhydrazine even exhibited strong inhibitory effects after oral administration.