New Oxadiazole Derivatives Showing partly Antiplatelet, Antithrombotic and Serotonin Antagonistic Properties

Ten new 1, 2, 4‐oxadiazole‐ and six new 1, 3, 4‐oxadiazole‐carboxamides containing different lipophilic moieties (i.e. 4‐biphenyl‐, 1‐naphthyl, phenylpropyl‐ and n‐hexyl substituents) and additional basic groups which are mainly alkyl‐ and dialkylaminoalkyl residues have been synthesized and tested for antiplatelet effects in vitro (Born‐test) and antithrombotic properties in vivo (laser thrombosis model). If the platelet aggregation was induced by collagen, the inhibitory effects (IC50) were between 58 μM and 300 μM. Using serotonin (5‐HT) as an inducer, compound 6a (N‐(3‐dimethylaminopropyl‐5‐(biphenyl‐4‐yl)‐1, 3, 4‐oxadiazole‐2‐carboxamide) had an IC50 = 1 μM ( 12e : (N‐3‐Dimethylaminopropyl)‐3‐(1‐naphthyl)‐1, 2, 4‐oxadiazole‐5‐carboxamide, 6.7 μM). In an in vitro rat tail artery assay 6a and 12e behaved as a competitive 5‐HT2A receptor antagonist ( 6a : pKB = 6.86 ± 0.04; 12e : pKB = 6.66 ± 0.05). The antithrombotic effects of some compounds were small but significant (7–10 % inhibition of thrombus formation).