A Thiazole Compound with Potential Antithrombotic Activity

Summary

A thiazole derivative, 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)-thiazole was found to be a potent inhibitor of collagen-induced platelet aggregation, in vitro, using platelets from at least six species, including man. It was active in human platelet-rich plasma at a concentration of 1 ng/ml. While its antiplatelet activity was greater than that of flurbiprofen, its cyclooxygenase activity was equivalent to that of flurbiprofen. Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test. The thiazole derivative inhibited platelet aggregation following oral administration in five laboratory species. In the guinea pig it was active at 0.5 mg/kg. The LD₅₀ in mice was greater than 1000 mg/kg (i.p.). This compound, which was designed through a systematic drug development program, may have high potential as an antithrombotic agent.

Key words

Antithrombotic agent - Platelet aggregation - Collagen inhibitor - Thiazole - Oral activity

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