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
