New NO-donors with antithrombotic and vasodilating activities, XII: Mesoionic oxatriazoles and related noncyclic nitrosohydrazine derivatives

Mesoionic 1,2,3,4-oxatriazolimines and the corresponding oxatriazolones were prepared and tested for their antiplatelet and antithrombotic activities. In the Born-test 5-amino-3-phenyl-1,2,3,4-oxatriazolimine chloride inhibited the platelet aggregation halfmaximally in a concentration 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. administration). These effects appear to be related to the formation of intermediate nitrosohydrazine derivatives. This aspect was supported by the activities in noncyclic nitrosohydrazines (2 compds.), nitrosohydrazones (2) and nitrosohydrazides (11). Five of them exhibited an IC50 < 100 nmol/L in the Born-test. In a thrombotic model strong inhibition of thrombus formation was observed after intravenous application. The 1-nitroso-1-benzylhydrazine even exhibited strong inhibitory effects after oral administration.