858100-00-2Relevant academic research and scientific papers
New oxadiazole derivatives showing partly antiplatelet, antithrombotic and serotonin antagonistic properties
Bethge, Katrin,Pertz, Heinz H.,Rehse, Klaus
, p. 78 - 86 (2005)
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).
