Characterization of imidazo[1,5-a]pyridine-5-hexanoic acid (CGS 13080) as a selective thromboxane synthetase inhibitor using and biochemical models |
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Authors: | Edmond C. Ku Stephen E. McPherson Carol Signor Herbert Chertock William D. Cash |
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Affiliation: | Research and Development Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Ardsley, New York 10502 USA |
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Abstract: | CGS 13080 inhibited cell-free thromboxane synthetase with an IC50 of 3 nM. It was at least five orders of magnitude less potent toward other key enzymes involved in arachidonic acid metabolism. Submicromolar concentrations inhibited calcium ionophore-induced formation of thromboxane B2 by intact human platelets with concomitant accumulation of prostaglandin E2. Oral doses lower than 1 mg/kg in rats suppressed the elevations of plasma thromboxane B2 induced by calcium ionophore. This was attended by shunting of endoperoxide substrate to 6-keto-prostaglandin F1α and prostaglandin E2. CGS 13080 is one of the most potent and selective thromboxane synthetase inhibitors yet identified. |
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