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 microM and 300 microM. 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 microM (12e: (N-3-Dimethylaminopropyl)-3-(1-naphthyl)-1, 2, 4-oxadiazole-5-carboxamide, 6.7 microM). 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).
Oxadiazole carboxamides (VI) and (XII) incorporating lipophilic moieties as well as basic residues are synthesized and tested for antiplatelet effects in vitro and antithrombotic properties in vivo. 1,3,4-Oxadiazoles (VI) having a lipophilic biphenyl rest and basic secondary or tertiary amines show antiaggregatory activity when the aggregation is induced by collagen. 1,2,4-Oxadiazoles (XII) reveal a similar activity pattern. Platelet aggregation induced by serotonin is inhibited by rather small concentrations of (VIb) and (XIIb). Compounds (VIa), (VIc), and (VId) display little but significant antithrombotic activities. -(BETHGE, K.; PERTZ, H. H.; REHSE*, K.; Arch. Pharm. (Weinheim, Ger.) 338 (2005) 2-3, 78-86; Inst.
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