Activity of a novel dual thromboxane A2receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles

Activity of a novel dual thromboxane A2receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles

The pharmacomodulation of sulfonylureas structurally related to torasemide and characterized by a TXA2antagonism led to the synthesis of BM-573. This original molecule showed a high affinity (IC501.3 nM) for the TXA2receptor of human platelets in comparison with both reference compounds, SQ-29548 (I...

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Veröffentlicht in:Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2001-08, Vol.65 (2), p.67-72
Hauptverfasser: Rolin, S., Dogné, J.M., Michaux, C., Delarge, J., Masereel, B.
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container_end_page 72
container_issue 2
container_start_page 67
container_title Prostaglandins, leukotrienes and essential fatty acids
container_volume 65
creator Rolin, S.
Dogné, J.M.
Michaux, C.
Delarge, J.
Masereel, B.
description The pharmacomodulation of sulfonylureas structurally related to torasemide and characterized by a TXA2antagonism led to the synthesis of BM-573. This original molecule showed a high affinity (IC501.3 nM) for the TXA2receptor of human platelets in comparison with both reference compounds, SQ-29548 (IC5021 nM) and sulotroban (IC50930 nM). Moreover, this torasemide derivative was found to be a potent inhibitor of human platelet aggregation induced by arachidonic acid (ED100=0.13 μM) or by U-46619 (ED50=0.24 μM), a TXA2agonist. BM-573 relaxed the isolated rat thoracic aorta (ED50=28.4 nM) and guinea-pig trachea (ED50=17.7 nM) contracted by U-46619. BM-573 (1 μM) completely reduced the platelet production of TXB2induced by arachidonic acid. Finally, BM-573 (30 mg/kg, per os) lost the diuretic properties of torasemide in rats.
doi_str_mv 10.1054/plef.2001.0290
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title Activity of a novel dual thromboxane A2receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles
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