Synthesis and pharmacological evaluation of BM-613, an original thromboxane A2 antagonist

Poster (2003, May)

hemodynamic effect of thromboxane A2 inhibition in acute pulmonary embolism

Poster (2003)

Pharmacological evaluation of the novel thromboxane modulator BM-567 (I/II). Effects of BM-567 on platelet function

in Prostaglandins, Leukotrienes, and Essential Fatty Acids (2003)

Antithrombotic activity of BM-573, a novel thromboxane modulator, in rat arterial thrombosis model, pig myocardial infarction model and its effect on bleeding time

in Blood (2003)

Pharmacology of the Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor Bm-531

in Cardiovascular Drug Reviews (2001), 19(2, Summer), 87-96

BM-531 (N-tert-butyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, is a novel noncarboxylic thromboxane receptor antagonist and thromboxane synthase inhibitor. Indeed, its ... [more ▼]

BM-531 (N-tert-butyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, is a novel noncarboxylic thromboxane receptor antagonist and thromboxane synthase inhibitor. Indeed, its affinity for human washed platelet TXA2 receptors labeled with [3H]SQ-29548 (IC50 = 0.0078 microM) is higher than sulotroban (IC50 = 0.93 microM) and SQ-29548 (IC50 = 0.021 microM). Moreover, BM-531 is characterized by a potent antiaggregatory property. Indeed, on one hand, in human citrated platelet-rich plasma BM-531 prevents platelet aggregation induced by arachidonic acid (600 microM) (ED100 = 0.125 microM), U-46619, a stable TXA2 agonist (1 microM) (ED50 = 0.482 microM) or collagen (1 microgram/mL) (percentage of inhibition: 42.9% at 10 microM) and inhibits the second wave of ADP (2 microM)-induced aggregation. On the other hand, when BM-531 is incubated in whole blood from healthy donors, the closure time measured by the recently developed platelet function analyser (PFA-100) is significantly prolonged. In addition, at the concentrations of 10 and 1 microM, BM-531 totally prevents the production of TXB2 by human platelets activated by arachidonic acid. Finally, at 10 microM, BM-531 significantly prevents rat fundus contractions induced by U-46619 but not by prostacyclin. These results suggest that BM-531, which is devoid of the diuretic property of torasemide, can be regarded as a promising antiplatelet agent. [less ▲]

Characterization of antiplatelet activity of ticlopidine and acetylsalicylic acid by PFA-100

in Fundamental & Clinical Pharmacology (2000), 14

Characterization of antiplatelet activity of ticlopidine and acetylsalicylic acid by PFA-100

Poster (1999, November 20)