New Oxadiazole Derivatives Showing partly Antiplatelet, Antithrombotic and Serotonin Antagonistic Properties
- 1 March 2005
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 338 (2-3), 78-86
- https://doi.org/10.1002/ardp.200400927
Abstract
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).Keywords
This publication has 19 references indexed in Scilit:
- New Antithrombotics with an Indazole StructureArchiv der Pharmazie, 2004
- Antiaggregating and Antithrombotic Activities of new 1, 2, 3‐TriazolecarboxamidesArchiv der Pharmazie, 2004
- Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XV: Antithrombotic Effect of Selected Oligoamines in RatsArchiv der Pharmazie, 1991
- Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factorNature, 1987
- Zur Herstellung von 1,3,4‐ Oxadiazol‐2‐carbonsäurederivatenJournal für Praktische Chemie, 1985
- The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholineNature, 1980
- Aggregation of Blood Platelets by Adenosine Diphosphate and its ReversalNature, 1962
- Über die Darstellung von Oxal‐hydrazidsäureesterEuropean Journal of Inorganic Chemistry, 1911
- Untersuchungen über NaphtoësäurenEuropean Journal of Inorganic Chemistry, 1887
- Ueber PhenyläthenylamidoximEuropean Journal of Inorganic Chemistry, 1885